curcumin and Inflammation

Due to their plasticity, macrophages exert critical effects on both promoting and suppressing inflammatory processes. Pathologic inflammatory conditions are frequently correlated with dynamic alterations in macrophage activation, with classically activated M1 cells associated with the promotion and maintenance of inflammation and M2 cells being linked to the resolution or smouldering of chronic inflammation. Inflammation deputes a common feature of various chronic diseases and the direct involvement in the insurgence and development of these conditions. Macrophages participate in an autoregulatory loop characterizing the inflammatory process, as they produce a wide range of biologically active mediators that exert either deleterious or beneficial effects during the inflammation. Therefore, balancing the favorable ratios of M1/M2 macrophages can help ameliorate the inflammatory landscape of pathologic conditions. Curcumin is a component of turmeric with many pharmacological properties.. Recent results from both in-vivo and in-vitro studies have indicated that curcumin can affect polarization and/or functions of macrophage subsets in the context of inflammation-related diseases. There is no comprehensive review of the impact of curcumin on cytokines involved in macrophage polarization in the context of inflammatory diseases. The present review will cover some efforts to explore the underlying molecular mechanisms by which curcumin modulates the macrophage polarization in distant pathological inflammatory conditions, such as cancer, autoimmunity, renal inflammation, stroke, atherosclerosis, and macrophage-driven pathogenesis.. The accumulation of the findings from in vitro and in vivo experimental studies suggests that curcumin beneficially influences M1 and M2 macrophages in a variety of inflammatory diseases with unfavorable macrophage activation.. Curcumin not only enhances anti-tumor immunity (via shifting M polarization towards M1 phenotype and/or up-regulation of M1 markers expression) but ameliorates inflammatory diseases, including autoimmune diseases (experimental autoimmune myocarditis and Behcet's disease), nephropathy, chronic serum sickness, stroke, and atherosclerosis.

Topics: Atherosclerosis; Curcumin; Humans; Inflammation; Macrophage Activation; Macrophages

Curcumin is the main active constituent of the medicinal plant Curcuma longa L., used traditionally as a medicinal spice in several ancient civilizations. Different preclinical and clinical studies support the anti-inflammatory properties of curcumin in various inflammatory diseases. As inflammation has an essential role in the pathophysiology of many ocular diseases, curcumin has been suggested as a promising therapeutic agent with anti-inflammatory properties. Based on the extent of experimental and clinical evidence, curcumin can exert protective effects against the corneal, uveal, retinal, optic nerve, orbital, and lacrimal gland inflammatory disorders. Herein, the available literature on the beneficial effects of curcumin in inflammatory eye diseases is reviewed. The limitations and future directions of these investigations are also discussed.

Topics: Anti-Inflammatory Agents; Curcumin; Eye Diseases; Inflammation; Plants, Medicinal; Vascular Diseases

Spinal cord injury (SCI) is an irreversible disease process with a high disability and mortality rate. After primary spinal cord injury, the secondary injury may occur in sequence, which is composed of ischemia and hypoxia, excitotoxicity, calcium overload, oxidative stress and inflammation, resulting in massive death of parenchymal cells in the injured area, followed by the formation of syringomyelia. Effectively curbing the process of secondary injury can promote nerve repair and improve functional prognosis. As the main active ingredient in turmeric, curcumin can play an important role in reducing inflammation and oxidation, protecting the neurons, and ultimately reducing spinal cord injury. This article reviews the effects of curcumin on the repair of nerve injury, with emphasis on the various mechanisms by which curcumin promotes the treatment of spinal cord injury.

Topics: Curcumin; Humans; Inflammation; Neuroprotective Agents; Oxidative Stress; Spinal Cord; Spinal Cord Injuries

Physical activity in general and sports in particular, is a mechanism that produces stress and generates great force in the tendon and in the muscle-tendon unit, which increases the risk of injury (tendinopathies). Eccentric and repetitive contraction of the muscle precipitates persistent microtraumatism in the tendon unit. In the development of tendinopathies, the cellular process includes inflammation, apoptosis, vascular, and neuronal changes. Currently, treatments with oral supplements are frequently used. Curcumin seems to preserve, and even repair, damaged tendons. In this systematic review, we focus more especially on the benefits of curcumin. The biological actions of curcumin are diverse, but act around three systems: (a) inflammatory, (b) nuclear factor B (NF-κB) related apoptosis pathways, and (c) oxidative stress systems. A bibliographic search is conducted under the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) as a basis for reporting reliable systematic reviews to perform a Scoping review. After analysing the manuscripts, we can conclude that curcumin is a product that demonstrates a significant biological antialgic, anti-inflammatory, and antioxidant power. Therefore, supplementation has a positive effect on the inflammatory and regenerative response in tendinopathies. In addition, curcumin decreases and modulates the cell infiltration, activation, and maturation of leukocytes, as well as the production of pro-inflammatory mediators at the site of inflammation.

Topics: Curcumin; Humans; Inflammation; Myotendinous Junction; Tendinopathy; Tendons

Orbital fibroblasts (OF) are considered the central target cells in the pathogenesis of thyroid-associated orbitopathy (TAO), which comprises orbital inflammation, orbital tissue edema, adipogenesis, fibrosis, oxidative stress and autophagy. Certain active ingredients of traditional Chinese medicine (TCM) demonstrated inhibition of TAO-OF in pre-clinical studies and they could be translated into novel therapeutic strategies.. The pertinent and current literature of pre-clinical studies on TAO investigating the effects of active ingredients of TCM was reviewed using the NCBI PubMed database.. Eleven TCM compounds demonstrated inhibition of TAO-OF in-vitro and three of them (polydatin, curcumin, and gypenosides) resulted in improvement in TAO mouse models. Tanshinone IIA reduced inflammation, oxidative stress and adipogenesis. Both resveratrol and its precursor polydatin displayed anti-oxidative and anti-adipogenic properties. Celastrol inhibited inflammation and triptolide prevented TAO-OF activation, while icariin inhibited autophagy and adipogenesis. Astragaloside IV reduced inflammation via suppressing autophagy and inhibited fat accumulation as well as collagen deposition. Curcumin displayed multiple actions, including anti-inflammatory, anti-oxidative, anti-adipogenic, anti-fibrotic and anti-angiogenic effects via multiple signaling pathways. Gypenosides reduced inflammation, oxidative stress, tissue fibrosis, as well as oxidative stress mediated autophagy and apoptosis. Dihydroartemisinin inhibited OF proliferation, inflammation, hyaluronan (HA) production, and fibrosis. Berberine attenuated inflammation, HA production, adipogenesis, and fibrosis.. Clinical trials of different phases with adequate power and sound methodology will be warranted to evaluate the appropriate dosage, safety and efficacy of these compounds in the management of TAO.

Topics: Animals; Curcumin; Fibroblasts; Fibrosis; Graves Ophthalmopathy; Inflammation; Medicine, Chinese Traditional; Mice

The main aim of the current study was to summarize the findings of available clinical studies to assess nano-curcumin's influence on COVID patients. A comprehensive online search was performed in Scopus, PubMed, ISI Web of Science, and Google Scholar until March 2022 to identify trials that investigated the effects of nano-curcumin in patients with COVID-19. Eight studies comprising 569 patients were included in this review. Compared with placebo, nano-curcumin had no significant effect on C-reactive protein (CRP) and high-sensitivity C-reactive protein (hs-CRP), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6). However, gene expression of IL-6 and gene expression as well as secretion of interleukin-1 beta (IL-1β) significantly decreased following nano-curcumin intervention. Nano-curcumin had beneficial effects on fever, cough, chills, myalgia, and olfactory and taste disturbances. The duration of hospitalization and mortality rate were significantly lower in the nano-curcumin group compared with the control group. Lymphocyte count was significantly increased after curcumin supplementation. Nano-curcumin also had favorable effects on O

Topics: C-Reactive Protein; COVID-19; Curcumin; Humans; Inflammation; Interleukin-6

Turmeric and its prominent bioactive compound, curcumin, have been the subject of many investigations with regard to their impact on inflammatory and oxidative balance in the body. In this systematic review and meta-analysis, we summarized the existing literature on randomized controlled trials (RCTs) which examined this hypothesis. Major databases (PubMed, Scopus, Web of Science, Cochrane Library and Google Scholar) were searched from inception up to October 2022. Relevant studies meeting our eligibility criteria were obtained. Main outcomes included inflammatory markers (i.e. C-reactive protein(CRP), tumour necrosis factorα(TNF-α), interleukin-6(IL-6), and interleukin 1 beta(IL-1β)) and markers of oxidative stress (i.e. total antioxidant capacity (TAC), malondialdehyde(MDA), and superoxide dismutase (SOD) activity). Weighted mean differences (WMDs) were reported. P-values < 0.05 were considered significant. Sixty-six RCTs were included in the final analysis. We observed that turmeric/curcumin supplementation significantly reduces levels of inflammatory markers, including CRP (WMD: -0.58 mg/l, 95 % CI: -0.74, -0.41), TNF-α (WMD: -3.48 pg/ml, 95 % CI: -4.38, -2.58), and IL-6 (WMD: -1.31 pg/ml, 95 % CI: -1.58, -0.67); except for IL-1β (WMD: -0.46 pg/ml, 95 % CI: -1.18, 0.27) for which no significant change was found. Also, turmeric/curcumin supplementation significantly improved anti-oxidant activity through enhancing TAC (WMD = 0.21 mmol/l; 95 % CI: 0.08, 0.33), reducing MDA levels (WMD = -0.33 µmol /l; 95 % CI: -0.53, -0.12), and SOD activity (WMD = 20.51 u/l; 95 % CI: 7.35, 33.67). It seems that turmeric/curcumin supplementation might be used as a viable intervention for improving inflammatory/oxidative status of individuals.

Topics: Adult; Anti-Inflammatory Agents; Antioxidants; Biomarkers; C-Reactive Protein; Curcuma; Curcumin; Dietary Supplements; Humans; Inflammation; Interleukin-6; Oxidative Stress; Randomized Controlled Trials as Topic; Superoxide Dismutase; Tumor Necrosis Factor-alpha

As the greatest defense organ of the body, the skin is exposed to endogenous and external stressors that produce reactive oxygen species (ROS). When the antioxidant system of the body fails to eliminate ROS, oxidative stress is initiated, which results in skin cellular senescence, inflammation, and cancer. Two main possible mechanisms underlie oxidative stress-induced skin cellular senescence, inflammation, and cancer. One mechanism is that ROS directly degrade biological macromolecules, including proteins, DNA, and lipids, that are essential for cell metabolism, survival, and genetics. Another one is that ROS mediate signaling pathways, such as MAPK, JAK/STAT, PI3K/AKT/mTOR, NF-κB, Nrf2, and SIRT1/FOXO, affecting cytokine release and enzyme expression. As natural antioxidants, plant polyphenols are safe and exhibit a therapeutic potential. We here discuss in detail the therapeutic potential of selected polyphenolic compounds and outline relevant molecular targets. Polyphenols selected here for study according to their structural classification include curcumin, catechins, resveratrol, quercetin, ellagic acid, and procyanidins. Finally, the latest delivery of plant polyphenols to the skin (taking curcumin as an example) and the current status of clinical research are summarized, providing a theoretical foundation for future clinical research and the generation of new pharmaceuticals and cosmetics.

Topics: Antioxidants; Carcinogenesis; Cellular Senescence; Curcumin; Humans; Inflammation; Neoplasms; Oxidative Stress; Phosphatidylinositol 3-Kinases; Polyphenols; Reactive Oxygen Species

Topics: Anti-Inflammatory Agents; Clinical Trials as Topic; Curcuma; Curcumin; Dietary Supplements; Humans; Inflammation; Osteoarthritis; Randomized Controlled Trials as Topic

Accumulating evidence has suggested that curcumin may protect against cerebral ischemia-reperfusion injury (CIRI). However, biological mechanisms vary across studies, limiting the clinical applicability of these findings. We performed a meta-analysis on publications evaluating curcumin administration in rat models of CIRI. Furthermore, we sought to test the hypothesis that curcumin alleviates CIRI through diminishing oxidation and inflammation. We searched PubMed, Embase, Web of Science, and Cochrane from the starting date of each database to May 2022 for experimental rat studies exploring the use of curcumin after ischemia reperfusion. Included articles were assessed for bias using SYRCLE's risk of bias tool. Data were aggregated by a random effects model. Curcumin administration significantly reduced neurological deficit score (20 studies; pooled mean difference [MD] = -1.57; 95% CI, -1.78 to -1.36, P < .00001), infarct volume (18 studies; pooled MD = -17.56%; 95% CI, -20.92% to -14.20%; P < 0.00001), and brain water content (8 studies, pooled MD = -11.29%, 95% CI: -16.48%, -6.11%, P < .00001). Compared with control, the levels of superoxide dismutase, glutathione, and glutathione peroxidase were significantly higher, whereas the levels of reactive oxygen species, malondialdehyde, interleukin-1β, interleukin-6, interleukin-8, and nuclear factor kappa B were significantly lower (P < .05). Subgroup analysis raised the possibility that intervention affections differed by curcumin's dose. To our knowledge, this is the first meta-analysis of curcumin's neuroprotection and mechanisms in rat CIRI models. Our analysis suggests the neuroprotective potential of curcumin in CIRI via antioxidant activity and anti-inflammatory effect. More research is required to further confirm the effectiveness and safety of curcumin on ischemic stroke therapy.

Topics: Animals; Antioxidants; Brain Ischemia; Curcumin; Inflammation; Ischemia; Neuroprotective Agents; Oxidative Stress; Rats; Reperfusion Injury

Curcumin (CUR) has been discovered to have many biological activities, including anti-inflammatory, anti-cancer, anti-oxygenation, anti-human immunodeficiency virus, anti-microbial and exhibits a good effect on the prevention and treatment of many diseases. However, the limited properties of CUR, including the poor solubility, bioavailability and instability caused by enzymes, light, metal irons, and oxygen, have compelled researchers to turn their attention to drug carrier application to overcome these drawbacks. Encapsulation may provide potential protective effects to the embedding materials and/or have a synergistic effect with them. Therefore, nanocarriers, especially polysaccharides-based nanocarriers, have been developed in many studies to enhance the anti-inflammatory capacity of CUR. Consequently, it's critical to review current advancements in the encapsulation of CUR using polysaccharides-based nanocarriers, as well as further study the potential mechanisms of action where polysaccharides-based CUR nanoparticles (the complex nanoparticles/Nano CUR-delivery systems) exhibit their anti-inflammatory effects. This work suggests that polysaccharides-based nanocarriers will be a thriving field in the treatment of inflammation and inflammation-related diseases.

Topics: Curcumin; Drug Carriers; Humans; Inflammation; Nanoparticles; Polysaccharides

Migraine, a neurovascular condition, is a chronic and lifelong disease that affects about 15% of the population worldwide. Although the exact pathophysiology and etiology of migraine are still unclear, oxidative stress, inflammation, and neuroendocrine imbalances are identified as the critical risk factors for migraine attacks. Curcumin is an active component and a polyphenolic diketone compound extracted from turmeric. Curcumin is a promising candidate for preventing and controlling migraine due to its anti‑inflammatory, antioxidative, anti-protein aggregate, and analgesic effects. In the present review, we have evaluated experimental and clinical studies investigating the impact of liposomal curcumin and nano-curcumin on the frequency and severity of migraine attacks in patients. Although the results are promising, more studies should be conducted in this area to show the exact efficacies of curcumin on clinical symptoms of migraine and investigate its potential mechanisms.

Topics: Antioxidants; Curcumin; Humans; Inflammation; Migraine Disorders; Oxidative Stress

Advanced chronic kidney disease (CKD) stages lead to exacerbated inflammation and oxidative stress. Patients with CKD in stage 5 need renal hemodialysis (HD) to remove toxins and waste products. However, this renal replacement therapy is inefficient in controlling inflammation. Regular curcumin consumption has been shown to reduce inflammation and oxidative stress in subjects with chronic pathologies, suggesting that the daily intake of curcumin may alleviate these conditions in HD patients. This review analyzes the available scientific evidence regarding the effect of curcumin intake on oxidative stress and inflammation in HD patients, focusing on the mechanisms and consequences of HD and curcumin consumption. The inclusion of curcumin as a dietary therapeutic supplement in HD patients has shown to control the inflammation status. However, the optimal dose and oral vehicle for curcumin administration are yet to be determined. It is important to consider studies on curcumin bioaccessibility to design effective oral administration vehicles. This information will contribute to the achievement of future nutritional interventions that validate the efficacy of curcumin supplementation as part of diet therapy in HD.

Topics: Curcumin; Humans; Inflammation; Oxidative Stress; Renal Dialysis; Renal Insufficiency, Chronic

Sarcopenia is the progressive loss of muscle mass, strength, and functions as we age. The pathogenesis of sarcopenia is underlined by oxidative stress and inflammation. As such, it is reasonable to suggest that a natural compound with both antioxidant and anti-inflammatory activities could prevent sarcopenia. Curcumin, a natural compound derived from turmeric with both properties, could benefit muscle health. This review aims to summarise the therapeutic effects of curcumin on cellular, animal, and human studies. The available evidence found in the literature showed that curcumin prevents muscle degeneration by upregulating the expression of genes related to protein synthesis and suppressing genes related to muscle degradation. It also protects muscle health by maintaining satellite cell number and function, protecting the mitochondrial function of muscle cells, and suppressing inflammation and oxidative stress. However, it is noted that most studies are preclinical. Evidence from randomised control trials in humans is lacking. In conclusion, curcumin has the potential to be utilised to manage muscle wasting and injury, pending more evidence from carefully planned human clinical trials.

Topics: Aging; Animals; Curcumin; Humans; Inflammation; Muscle, Skeletal; Muscular Atrophy; Oxidative Stress; Sarcopenia

The aim of this study is to evaluate the effectiveness and safety of curcumin in rheumatoid arthritis patients.. A computerized search from PubMed, Embase, Cochrane Library, and Web of Science databases was performed until 3 March 2023. Literature screening, basic data extraction and risk of bias evaluation were independently performed by two researchers each. The quality evaluation of the literature was performed according to the Cochrane Handbook for Risk of Bias Assessment tool for treatment evaluation.. The current study includes six publications covering 539 rheumatoid arthritis patients. The activity of rheumatoid arthritis was assessed using erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), protein, disease activity score (DAS), rheumatoid factor (RF), Visual Analogue Scale (VAS) pain, tender joint count (TJC) and swollen joint count (SJC). ESR (MD = -29.47, 95% CI [-54.05, -4.88], Z=2.35, P = 0.02), DAS28 (MD = -1.20, 95% CI [-1.85, -0.55], Z=3.62, P = 0.0003), SJC (MD = -5.33, 95% CI [-9.90, -0.76], Z = 2.29, P = 0.02) and TJC (MD = -6.33, 95% CI [-10.86, -1.81], Z = 2.74, P = 0.006) showed significantly change in experimental patients compared with controls.. Curcumin is beneficial for rheumatoid arthritis treatment. Inflammation levels and clinical symptoms in patients with rheumatoid arthritis can be improved by curcumin supplementation. Large sample randomized controlled trials on the effects of curcumin on patients with rheumatoid arthritis are needed in the future.. https://www.crd.york.ac.uk/PROSPERO/, identifier (CRD42022361992).

Topics: Arthritis, Rheumatoid; C-Reactive Protein; Curcumin; Humans; Inflammation; Rheumatoid Factor

It has been for thousands of years in China known medicinal homologous foods that can be employed both as foods and medicines to benefit human and animal health. These edible herbal materials perform divert roles in the regulation of metabolic disorders, cancers, and immune-related diseases. Curcumin, the primary component derived from medicinal homologous foods like curcuma longa rhizome, is reported to play vital actions in organic activities, such as the numerous pharmacological functions including anti-oxidative stress, anti-inflammation and anti/pro-apoptosis in treating various diseases. However, the potential mechanisms of curcumin-derived modulation still need to be developed and attract more attention worldwide. Given that these signal pathways are enrolled in important bioactive reactions, we collected curcumin's last achievements predominantly on the immune-regulation signals with the underlying targetable strategies in the last 10 years. This mini-review will be helpful to accelerate curcumin and other extracts from medicinal homologous foods use in future human clinical applications.

Topics: Animals; Anti-Inflammatory Agents; Apoptosis; Curcumin; Humans; Inflammation; Oxidative Stress

The aim was to conduct a systematic review and meta-analysis for assessing the effectiveness and safety of dietary polyphenol curcumin supplement on metabolic, inflammatory, and oxidative stress indices in patients with metabolic syndrome (MetS).. A comprehensive search for clinical trials was conducted in the following scientific databases: PubMed, SCOPUS, Cochrane Library, EMBASE, Web of Science, and China Biological Medicine. Randomized controlled trials (RCTs) evaluating the efficacy and safety of curcumin supplement for MetS were identified. A random-effects meta-analysis was performed using inverse variance, and efficacy was expressed as mean difference (MD) with 95% confidence interval (CI). The metabolic syndrome markers that were evaluated in the present study included waist circumference (WC), fasting blood sugar (FBS), systolic blood pressure (SBP), diastolic blood pressure (DBP), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), tumor necrosis factor-a (TNF-a), interleukin 6 (IL-6), C-reactive protein (CRP), ultrasensitive c-reactive protein (hsCRP), and malondialdehyde (MDA). By employing the Cochrane tool, RCTs were assessed for bias risk.. A total of 785 participants from 13 RCTs were included, with intervention durations ranging from 4 to 12 weeks. Compared with the control group, the curcumin group had positive effects on WC (MD = -2.16, 95% CI: -3.78 to -0.54,. Curcumin exhibited promising potential in enhancing markers associated with metabolic syndrome, including inflammation. However, additional studies are required to confirm such findings since the included evidence is limited and has a relatively high heterogeneity.. https://www.crd.york.ac.uk/prospero, identifier CRD42022362553.

Topics: Curcuma; Curcumin; Dietary Supplements; Humans; Inflammation; Metabolic Syndrome; Oxidative Stress; Polyphenols; Randomized Controlled Trials as Topic

It has been suggested that curcumin is a potential agent for lowering the levels of C-reactive protein (CRP) and high-sensitivity CRP (hs-CRP), as markers of inflammation. In the current meta-analysis, we attempted to clarify the efficacy of curcumin supplementation in lowering the concentrations of CRP and hs-CRP in patients with autoinflammatory conditions. Nine studies were found evaluating the effect of curcumin on CRP levels, while 23 studies were identified for hs-CRP. CRP concentration was decreased significantly compared to the placebo (WMD = -3.67 mg/L, 95% CI = -6.96 to -0.38, p = 0.02). There was a significant effect of curcumin at dose ≤1,000 mg/day on the CRP concentration. CRP concentration significantly decreased after >10-week intervention compared with placebo.hs-CRP concentration in the intervention group was significantly lower than that of placebo group. A significant effect of curcumin consumption was detected on the serum level of hs-CRP in studies with prescribing ≤1,000 mg/day, and those with ≤10-week duration of intervention. Curcumin consumption resulted in a reduction of hs-CRP in a non-linear fashion with stronger effects with less than 2000 mg curcumin per day. Curcumin seems to be beneficial in decreasing the hs-CRP and CRP levels in proinflammatory settings.

Topics: Biomarkers; C-Reactive Protein; Curcumin; Humans; Inflammation; Randomized Controlled Trials as Topic

Neuroinflammation is characterized by reactive microglia and astrocytes (collectively called gliosis) in the central nervous system and is considered as one of the main pathological hallmarks in different neurodegenerative diseases such as Alzheimer's disease, age-related dementia, and multiple sclerosis. Upon activation, glia undergoes structural and morphological changes such as the microglial cells swell in size and astrocytes become bushy, which play both beneficial and detrimental roles. Hence, they are unable to perform the normal physiological role in brain immunity. Curcumin, a cytokine suppressive anti-inflammatory drug, has a high proven pre-clinical potency and efficacy to reverse chronic neuroinflammation by attenuating the activation and morphological changes that occur in the microglia and astrocytes. This review will highlight the recent findings on the tree structure changes of microglia and astrocytes in neuroinflammation and the effects of curcumin against the activation and morphology of glial cells.

Topics: Astrocytes; Curcumin; Humans; Inflammation; Microglia; Neuroglia; Neuroinflammatory Diseases

Inflammaging is a term used to describe the tight relationship between low-grade chronic inflammation and aging that occurs during physiological aging in the absence of evident infection. This condition has been linked to a broad spectrum of age-related disorders in various organs including the brain. Inflammaging represents a highly significant risk factor for the development and progression of age-related conditions, including neurodegenerative diseases which are characterized by the progressive dysfunction and degeneration of neurons in the brain and peripheral nervous system. Curcumin is a widely studied polyphenol isolated from

Topics: Aging; Animals; Anti-Inflammatory Agents, Non-Steroidal; Brain; Curcumin; Humans; Inflammation; Microglia; Neurodegenerative Diseases

Systemic autoimmune diseases like rheumatoid arthritis, multiple sclerosis, and systemic lupus erythematosus represent various autoimmune conditions identified by immune system dysregulation. The activation of immune cells, auto-antigen outbreak, inflammation, and multi-organ impairment is observed in these disorders. The immune system is an essential complex network of cells and chemical mediators which defends the organism's integrity against foreign microorganisms, and its precise operation and stability are compulsory to avoid a wide range of medical complications. Curcumin is a phenolic ingredient extracted from turmeric and belongs to the Zingiberaceae, or ginger family. Curcumin has multiple functions, such as inhibiting inflammation, oxidative stress, tumor cell proliferation, cell death, and infection. Nevertheless, the immunomodulatory influence of curcumin on immunological reactions/processes remains mostly unknown. In the present narrative review, we sought to provide current information concerning the preclinical and clinical uses of curcumin in systemic autoimmune diseases.

Topics: Arthritis, Rheumatoid; Autoimmune Diseases; Curcumin; Humans; Inflammation; Lupus Erythematosus, Systemic

Curcumin is a natural product widely used due to its pharmacological effects. Nevertheless, only a limited number of studies concerning the effects of curcumin on exudative age‑related macular degeneration (AMD) is currently available. Since ophthalmic diseases, including exudative AMD, have a marked impact on public health, the prevention and therapy of ophthalmic disorders remain of increasing concern. Exudative AMD is characterized by choroidal neovascularization (CNV) invading the subretinal space, ultimately enhancing exudation and hemorrhaging. The exudative AMD subtype corresponds to 10 to 15% of cases of macular degeneration; however, the occurrence of this subtype has been reported as the major cause of vision loss and blindness, with the occurrence of CNV being responsible for 80% of the cases with vision loss. In CNV increased expression of VEGF has been observed, stimulated by the overactivation of Wnt/β‑catenin signaling pathway. The stimulation of the Wnt/β‑catenin signaling pathway is responsible for the activation of several cellular mechanisms, simultaneously enhancing inflammation, oxidative stress and angiogenesis in numerous diseases, including ophthalmic disorders. Some studies have previously demonstrated the possible advantage of the use of curcumin for the inhibition of Wnt/β‑catenin signaling. In the present review article, the different mechanisms of curcumin are described concerning its effects on oxidative stress, inflammation and angiogenesis in exudative AMD, by interacting with Wnt/β‑catenin signaling.

Topics: beta Catenin; Choroidal Neovascularization; Curcumin; Eye Diseases; Humans; Inflammation; Macular Degeneration; Wnt Signaling Pathway

To quantify the effects of curcumin supplementation on exercise-induced muscle damage, muscle soreness, inflammatory biomarkers, muscle strength, and joint flexibility via assessment of creatine kinase (CK), visual analogue scale (VAS) score, maximal voluntary contraction (MVC), and range of motion (ROM), respectively. Online databases, including PubMed, Google Scholar, and Scopus, were searched up to February 2021. RevMan® software (version 5.3) was used for assessing the risk of bias to assess the quality of studies. The mean differences (MD) and confidence intervals (95% CI) of CK activity (IU/L), VAS score, tumor necrosis factor (TNF-α) (pg/ml), interleukin-6 (IL-6) (pg/ml), IL-8 (pg/ml), MVC (nm) and ROM (degree) were pooled using a random- or fixed-effect model. Between-study heterogeneity was assessed using χ-square or I

Topics: Biomarkers; Curcumin; Dietary Supplements; Humans; Inflammation; Interleukin-6; Interleukin-8; Muscle Strength; Myalgia; Randomized Controlled Trials as Topic; Range of Motion, Articular; Tumor Necrosis Factor-alpha

Autoimmune diseases usually arise as a result of an aberrant immune system attack on normal tissues of the body, which leads to a cascade of inflammatory reactions. The immune system employs different types of protective and anti-inflammatory cells for the regulation of this process. Curcumin is a known natural anti-inflammatory agent that inhibits pathological autoimmune processes by regulating inflammatory cytokines and their associated signaling pathways in immune cells. Due to the unstable nature of curcumin and its susceptibility to either degradation, or metabolism into other chemical entities (i.e., metabolites), encapsulation of this agent into various nanocarriers would appear to be an appropriate strategy for attaining greater beneficial effects from curcumin as it pertains to immunomodulation. Many studies have focused on the design and development of curcumin nanodelivery systems (micelles, dendrimers, and diverse nanocarriers) and are summarized in this review in order to obtain greater insight into novel drug delivery systems for curcumin and their suitability for the management of autoimmune diseases.

Topics: Autoimmune Diseases; Curcumin; Drug Delivery Systems; Humans; Inflammation; Nanotechnology

Sadeq A. Al-Maweri, Mohammed Nasser Alhajj, Esraa A. Deshisha, Ameera K. Alshafei, Azza I. Ahmed, Nada O. Almudayfi, Sara A. Alshammari, Alla Alsharif, Saba Kassim (2021). Curcumin mouthwashes versus chlorhexidine in controlling plaque and gingivitis: A systematic review and meta-analysis. International Journal of Dental Hygiene. Pages 1-9.. Government? Industry? Non-profit, Foundations, etc? Other? Information not available?. Systematic review with meta-analysis of data.

Topics: Anti-Infective Agents, Local; Chlorhexidine; Curcumin; Dental Plaque; Gingivitis; Humans; Inflammation; Mouthwashes

Modern pharmacological research found that the chemical components of. Pubmed, Cochran Library, CNKI, and other databases were searched to collect the randomized controlled trials (RCTs). Then, the risk of bias of RCTs were assessed and data of RCTs were extracted. Finally, RevMan 5.3 was utilized for meta-analysis.. Twenty-nine (29) RCTs involving 2396 participants and 5 types of arthritis were included. The arthritis included Ankylosing Spondylitis (AS), Rheumatoid Arthritis (RA), Osteoarthritis (OA), Juvenile idiopathic arthritis (JIA) and gout/hyperuricemia. Curcumin and Curcuma longa Extract were administered in doses ranging from 120 mg to 1500 mg for a duration of 4-36 weeks. In general, Curcumin and Curcuma longa Extract showed safety in all studies and improved the severity of inflammation and pain levels in these arthritis patients. However, more RCTs are needed in the future to elucidate the effect of Curcumin and Curcuma longa Extract supplementation in patients with arthritis, including RA, OA, AS and JIA.. Curcumin and Curcuma longa Extract may improve symptoms and inflammation levels in people with arthritis. However, due to the low quality and small quantity of RCTs, the conclusions need to be interpreted carefully.

Topics: Arthritis, Rheumatoid; Curcuma; Curcumin; Humans; Inflammation; Osteoarthritis; Plant Extracts; Randomized Controlled Trials as Topic; Spondylitis, Ankylosing

Considerable interest continues to be focused on the development of curcumin either as an effective stand-alone therapeutic or as an adjunct therapy to established therapies. Curcumin (1, 7-bis (4-hydroxy-3-methoxyphenyl)-1, 6-heptadiene-3, 5- dione; also called diferuloylmethane) is a polyphenolic phytochemical extracted from the root of curcuma longa, commonly called turmeric. Despite evidence from in vitro (cell culture) and preclinical studies in animals, clinical studies have not provided strong evidence for a therapeutic effect of curcumin. The relevance of curcumin as a drug has been questioned based on its classification as a compound with pan assay interference and invalid metabolic panaceas properties bringing into question the relevance of the therapeutic targets identified for curcumin. To some extent this is due to the lack of a complete understanding of the link between the in vitro (cell culture activity), pharmacokinetics and in vivo activity of curcumin. In this review and using NF-κB as a cellular target for curcumin, we have investigated the relationship between the potency of curcumin as an inhibitor of NF-κB in cell culture, the pharmacokinetics of curcumin and curcumin's anticancer and anti-inflammatory effects in preclinical models of cancer and inflammation. Plausible explanations and rationale are provided to link these activities together and suggest that both curcumin and its more soluble Phase II metabolite curcumin glucuronide may play a key role in the treatment effects of curcumin in vivo mediated at NF-κB.

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Curcumin; Inflammation; NF-kappa B

Chronic inflammation of the respiratory tract is one of the most concerning public health issues, as it can lead to chronic respiratory diseases (CRDs), some of which are more detrimental than others. Chronic respiratory diseases include chronic obstructive pulmonary disease (COPD), asthma, lung cancer, and pulmonary fibrosis. The conventional drug therapies for the management and treatment of CRDs only address the symptoms and fail to reverse or recover the chronic-inflammation-mediated structural and functional damage of the respiratory tract. In addition, the low efficacy and adverse effects of these drugs have directed the attention of researchers towards nutraceuticals in search of potential treatment strategies that can not only ameliorate CRD symptoms but also can repair and reverse inflammatory damage. Hence, there is a growing interest toward investigating the medicinal benefits of nutraceuticals, such as rutin, curcumin, zerumbone, and others. Nutraceuticals carry many nutritional and therapeutic properties, including anti-inflammatory, antioxidant, anticancer, antidiabetic, and anti-obesity properties, and usually do not have as many adverse effects, as they are naturally sourced. Recently, the use of nanoparticles has also been increasingly studied for the nano drug delivery of these nutraceuticals. The discrete size of nanoparticles holds great potential for the level of permeability that can be achieved when transporting these nutraceutical compounds. This review is aimed to provide an understanding of the use of nutraceuticals in combination with nanoparticles against CRDs and their mechanisms involved in slowing down or reversing the progression of CRDs by inhibiting pro-inflammatory signaling pathways.

Topics: Anti-Inflammatory Agents; Antioxidants; Curcumin; Functional Food; Humans; Hypoglycemic Agents; Inflammation; Pulmonary Disease, Chronic Obstructive; Rutin

Curcumin is a polyphenolic compound derived from turmeric that has potential beneficial properties for cardiovascular and renal diseases and is relatively safe and inexpensive. However, the application of curcumin is rather problematic due to its chemical instability and low bioavailability. The experimental results showed improved chemical stability and potent pharmacokinetics of one of its analogs - (2E,6E)-2,6-bis[(2-trifluoromethyl)benzylidene]cyclohexanone (C66). There are several advantages of C66, like its synthetic accessibility, structural simplicity, improved chemical stability (in vitro and in vivo), presence of two reactive electrophilic centers, and good electron-accepting capacity. Considering these characteristics, we reviewed the literature on the application of C66 in resolving diabetes-associated cardiovascular and renal complications in animal models. We also summarized the mechanisms by which C66 is preventing the release of pro-oxidative and pro-inflammatory molecules in the priming and in activation stage of cardiomyopathy, renal fibrosis, and diabetic nephropathy. The cardiovascular protective effect of C66 against diabetes-induced oxidative damage is Nrf2 mediated but mainly dependent on JNK2. In general, C66 causes inhibition of JNK2, which reduces cardiac inflammation, fibrosis, oxidative stress, and apoptosis in the settings of diabetic cardiomyopathy. C66 exerts a powerful antifibrotic effect by reducing inflammation-related factors (MCP-1, NF-κB, TNF-α, IL-1β, COX-2, and CAV-1) and inducing the expression of anti-inflammatory factors (HO-1 and NEDD4), as well as targeting TGF-β/SMADs, MAPK/ERK, and PPAR-γ pathways in animal models of diabetic nephropathy. Based on the available evidence, C66 is becoming a promising drug candidate for improving cardiovascular and renal health.

Topics: Animals; Curcumin; Diabetes Mellitus, Experimental; Diabetic Nephropathies; Fibrosis; Inflammation; Kidney; Oxidative Stress

Topics: Animals; Antioxidants; Curcuma; Curcumin; Diabetes Mellitus, Type 2; Humans; Inflammation

Ulcerative colitis (UC) is one of the inflammatory bowel diseases (IBD). It is a chronic autoimmune inflammation of unclear etiology affecting the colon and rectum, characterized by unpredictable exacerbation and remission phases. Conventional treatment options for UC include mesalamine, glucocorticoids, immunosuppressants, and biologics. The management of UC is challenging, and other therapeutic options are constantly being sought. In recent years more attention is being paid to curcumin, a main active polyphenol found in the turmeric root, which has numerous beneficial effects in the human body, including anti-inflammatory, anticarcinogenic, and antioxidative properties targeting several cellular pathways and making an impact on intestinal microbiota. This review will summarize the current knowledge on the role of curcumin in the UC therapy.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Colitis, Ulcerative; Curcumin; Humans; Inflammation; Mesalamine

Colorectal cancer (CRC) is one of most common malignancies worldwide and its incidence is still growing. In spite of recent advances in targeted therapies, their clinical efficacy has been limited, non-curative and unaffordable. A growing body of literature indicates that CRC is a multi-modal disease, where a variety of factors within the tumor microenvironment play a significant role in its pathogenesis. For instance, imbalance in gut microbial profiles and impaired intestinal barrier function contribute to the overall intestinal inflammation and initiation of CRC. Moreover, persistent chronic inflammation favors a tumor microenvironment for the growth of cancer. In addition, autophagy or 'self-eating' is a surveillance mechanism involved in the degradation of cellular constituents that are generated under stressful conditions. Cancer stem cells (CSCs), on the other hand, engage in the onset of CRC and are able to endow cancer cells with chemo-resistance. Furthermore, the aberrant epigenetic alterations promote CRC. These evidences highlight the need for multi-targeted approaches that are not only safe and inexpensive but offer a more effective alternative to current generation of targeted drugs. Curcumin, derived from the plant Curcuma longa, represents one such option that has a long history of its use for a variety of chronic disease including cancer, in Indian ayurvedic and traditional Chinese medicine. Scientific evidence over the past few decades have overwhelmingly shown that curcumin exhibits a multitude of anti-cancer activities orchestrated through key signaling pathways associated with cancer. In this article, we will present a current update and perspective on this natural medicine - incorporating the basic cellular mechanisms it effects and the current state of clinical evidence, challenges and promise for its use as a cancer preventative and potential adjunct together with modern therapies for CRC patients.

Topics: Colorectal Neoplasms; Curcumin; Epigenomics; Humans; Inflammation; Signal Transduction; Tumor Microenvironment

Unprecedented community containment measures were taken following the recent outbreak of COVID-19 in Italy. The aim of the study was to explore the self-reported future compliance of citizens with such measures and its relationship with potentially impactful psychological variables.. An online survey was completed by 931 people (18-76 years) distributed across the Italian territory. In addition to demographics, five dimensions were measured: self-reported compliance with containment measures over time (today, at 7, 14, 30, 60, 90, and 180 days from now) at three hypothetical risk levels (10, 50, 90% of likelihood of contracting the COVID-19), perceived risk, generalized anxiety, intolerance of uncertainty, and relevance of several psychological needs whose satisfaction is currently precluded.. The duration of containment measures plays a crucial role in tackling the spread of the disease as people will be less compliant over time. Psychological needs of citizens impacting on the compliance should be taken into account when planning an easing of the lockdown, along with interventions for protecting vulnerable groups from mental distress.. La apendicitis aguda (AA) es la urgencia quirúrgica abdominal más frecuente. No encontramos estudios específicos que evalúen el impacto de la pandemia causada por el coronavirus 2 (SARS-Cov-2) sobre la AA y su tratamiento quirúrgico. Analizamos la influencia de esta nueva patología sobre la AA.. Estudio observacional retrospectivo en pacientes intervenidos por AA desde enero hasta abril de 2020. Fueron clasificados según el momento de la apendicectomía, antes de la declaración del estado de alarma (Pre-COVID19) y después de la declaración del estado de alarma (Post-COVID19) en España. Se evaluaron variables demográficas, duración de la sintomatología, tipo de apendicitis, tiempo quirúrgico, estancia hospitalaria y complicaciones postoperatorias.. La pandemia por SARS-Cov-2 influye en el momento de diagnóstico de la apendicitis, así como en su grado de evolución y estancia hospitalaria. La peritonitis fue lo más frecuentemente observado. Una sospecha y orientación clínica más temprana, es necesaria para evitar un manejo inadecuado de este trastorno quirúrgico común.. The primary outcome is improvement in PaO. Findings will provide timely information on the safety, efficacy, and optimal dosing of t-PA to treat moderate/severe COVID-19-induced ARDS, which can be rapidly adapted to a phase III trial (NCT04357730; FDA IND 149634).. None.. The gut barrier is crucial in cirrhosis in preventing infection-causing bacteria that normally live in the gut from accessing the liver and other organs via the bloodstream. Herein, we characterised gut inflammation by measuring different markers in stool samples from patients at different stages of cirrhosis and comparing this to healthy people. These markers, when compared with equivalent markers usually measured in blood, were found to be very different in pattern and absolute levels, suggesting that there is significant gut inflammation in cirrhosis related to different immune system pathways to that seen outside of the gut. This provides new insights into gut-specific immune disturbances that predispose to complications of cirrhosis, and emphasises that a better understanding of the gut-liver axis is necessary to develop better targeted therapies.. La surveillance de l’intervalle QT a suscité beaucoup d’intérêt durant la pandémie de la COVID-19 en raison de l’utilisation de médicaments prolongeant l’intervalle QT et les préoccupations quant à la transmission virale par les électrocardiogrammes (ECG) en série. Nous avons posé l’hypothèse que la surveillance en continu de l’intervalle QT par télémétrie était associée à une meilleure détection des épisodes de prolongation de l’intervalle QT.. Nous avons introduit la télémétrie cardiaque en continu (TCC) à l’aide d’un algorithme de surveillance automatisée de l’intervalle QT dans nos unités de COVID-19. Les mesures automatisées quotidiennes de l’intervalle QT corrigé (auto-QTc) en fonction de la fréquence cardiaque maximale ont été enregistrées. Nous avons comparé la proportion des épisodes de prolongation marquée de l’intervalle QTc (QTc long), définie par un intervalle QTc ≥ 500 ms, chez les patients montrant une suspicion de COVID-19 ou ayant la COVID-19 qui avaient été admis avant et après la mise en place de la TCC (groupe témoin. La surveillance en continu de l’intervalle QT est supérieure à la norme de soins dans la détection des épisodes de QTc long et exige peu d’ECG. La réponse clinique aux épisodes de QTc long est sous-optimale.. Exposure to a model wildfire air pollution source modifies cardiovascular responses to HC challenge, suggesting air pollution sensitizes the body to systemic triggers.. Though the majority of HIV-infected adults who were on HAART had shown viral suppression, the rate of suppression was sub-optimal according to the UNAIDS 90-90-90 target to help end the AIDS pandemic by 2020. Nonetheless, the rate of immunological recovery in the study cohort was low. Hence, early initiation of HAART should be strengthened to achieve good virological suppression and immunological recovery.. Dust in Egyptian laying hen houses contains high concentrations of microorganisms and endotoxins, which might impair the health of birds and farmers when inhaled. Furthermore, laying hens in Egypt seem to be a reservoir for ESBL-producing Enterobacteriaceae. Thus, farmers are at risk of exposure to ESBL-producing bacteria, and colonized hens might transmit these bacteria into the food chain.. The lack of significant differences in the absolute changes and relative ratios of injury and repair biomarkers by contrast-associated AKI status suggests that the majority of mild contrast-associated AKI cases may be driven by hemodynamic changes at the kidney.. Most comparisons for different outcomes are based on very few studies, mostly low-powered, with an overall low CoE. Thus, the available evidence is considered insufficient to either support or refute CH effectiveness or to recommend one ICM over another. Therefore, further well-designed, larger RCTs are required.. PROSPERO database Identifier: CRD42016041953.. Untouched root canal at cross-section perimeter, the Hero 642 system showed 41.44% ± 5.62% and Reciproc R40 58.67% ± 12.39% without contact with instruments. Regarding the untouched area, Hero 642 system showed 22.78% ± 6.42% and Reciproc R40 34.35% ± 8.52%. Neither instrument achieved complete cross-sectional root canal debridement. Hero 642 system rotary taper 0.02 instruments achieved significant greater wall contact perimeter and area compared to reciprocate the Reciproc R40 taper 0.06 instrument.. Hero 642 achieved higher wall contact perimeter and area but, regardless of instrument size and taper, vital pulp during. The functional properties of the main mechanisms involved in the control of muscle Ca. This study showed that the anti-inflammatory effect of the iron-responsive product DHA in arthritis can be monitored by an iron-like radioactive tracer (. Attenuated vascular reactivity during pregnancy suggests that the systemic vasodilatory state partially depletes nitric oxide bioavailability. Preliminary data support the potential for MRI to identify vascular dysfunction in vivo that underlies PE. Level of Evidence 2 Technical Efficacy Stage 1 J. MAGN. RESON. IMAGING 2021;53:447-455.. La evaluación de riesgo es importante para predecir los resultados postoperatorios en pacientes con cáncer gastroesofágico. Este estudio de cohortes tuvo como objetivo evaluar los cambios en la composición corporal durante la quimioterapia neoadyuvante e investigar su asociación con complicaciones postoperatorias. MÉTODOS: Los pacientes consecutivos con cáncer gastroesofágico sometidos a quimioterapia neoadyuvante y cirugía con intención curativa entre 2016 y 2019, identificados a partir de una base de datos específica, se incluyeron en el estudio. Se utilizaron las imágenes de tomografía computarizada, antes y después de la quimioterapia neoadyuvante, para evaluar el índice de masa muscular esquelética, la sarcopenia y el índice de grasa visceral y subcutánea.. In this in vitro premature infant lung model, HF oscillation of BCPAP was associated with improved CO. Our results showed that HPC significantly promotes neurogenesis after MCAO and ameliorates neuronal injury.. Inflammatory markers are highly related to signs of systemic hypoperfusion in CS. Moreover, high PCT and IL-6 levels are associated with poor prognosis.. These findings indicate that Tetrapleura tetraptera fruit has a protective potential against stroke through modulation of redox and electrolyte imbalances, and attenuation of neurotransmitter dysregulation and other neurochemical dysfunctions. Tetrapleura tetraptera fruit could be a promising source for the discovery of bioactives for stroke therapy.

Topics: 3T3-L1 Cells; A Kinase Anchor Proteins; Acetates; Achilles Tendon; Acute Kidney Injury; Acute Pain; Acyclic Monoterpenes; Adenine Nucleotides; Adhesins, Escherichia coli; Adipocytes; Adipocytes, Brown; Adipogenesis; Administration, Inhalation; Administration, Oral; Adrenal Cortex Hormones; Adsorption; Adult; Aeromonas hydrophila; Africa; Aged; Aged, 80 and over; Agrobacterium tumefaciens; Air; Air Pollutants; Air Pollution; Air Pollution, Indoor; Algorithms; Alkaloids; Alkynes; Allosteric Regulation; Amines; Amino Acid Sequence; Amino Acids; Amino Acids, Branched-Chain; Aminoisobutyric Acids; Aminopyridines; Amyotrophic Lateral Sclerosis; Anaerobic Threshold; Angiography; Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Animal Distribution; Animal Feed; Animal Nutritional Physiological Phenomena; Animals; Ankle Joint; Anti-Bacterial Agents; Anti-HIV Agents; Anti-Inflammatory Agents; Antibodies, Bacterial; Antifungal Agents; Antimalarials; Antineoplastic Agents; Antineoplastic Agents, Phytogenic; Antioxidants; Antiretroviral Therapy, Highly Active; Antiviral Agents; Aotidae; Apelin; Apoptosis; Arabidopsis Proteins; Argentina; Arginine; Artemisinins; Arthritis, Experimental; Arthritis, Rheumatoid; Arthroscopy; Aspergillus; Aspergillus niger; Asteraceae; Asthma; ATP Binding Cassette Transporter, Subfamily B, Member 1; ATP Binding Cassette Transporter, Subfamily G, Member 2; Auditory Cortex; Autoantibodies; Autophagy; Bacteria; Bacterial Infections; Bacterial Proteins; Bacterial Typing Techniques; Base Composition; Base Sequence; Basketball; Beclin-1; Benzhydryl Compounds; Benzimidazoles; Benzo(a)pyrene; Benzofurans; Benzoxazines; Bereavement; beta Catenin; beta-Lactamase Inhibitors; beta-Lactamases; beta-Lactams; Betacoronavirus; Betaine; Binding Sites; Biofilms; Biological Assay; Biological Availability; Biological Evolution; Biomarkers; Biomechanical Phenomena; Biopolymers; Biopsy; Bismuth; Blood Glucose; Blood Platelets; Blood Pressure; Body Composition; Body Weight; Bone Marrow; Bone Marrow Cells; Bone Regeneration; Boron; Botrytis; Brain Ischemia; Brain Neoplasms; Brain-Derived Neurotrophic Factor; Brazil; Breast Neoplasms; Breath Tests; Bronchoalveolar Lavage Fluid; Burkholderia; C-Reactive Protein; Caenorhabditis elegans; Caenorhabditis elegans Proteins; Calcification, Physiologic; Calcium; Calcium Signaling; Calorimetry, Differential Scanning; Cameroon; Camptothecin; Candida; Candida albicans; Capillaries; Carbapenem-Resistant Enterobacteriaceae; Carbapenems; Carbohydrate Conformation; Carbon; Carbon Dioxide; Carbon Isotopes; Carcinoma, Ovarian Epithelial; Cardiac Output; Cardiomyopathy, Hypertrophic; Cardiotonic Agents; Cardiovascular Diseases; Caregivers; Carps; Case-Control Studies; Catalase; Catalysis; Cats; CD4 Lymphocyte Count; Cell Culture Techniques; Cell Differentiation; Cell Line, Tumor; Cell Membrane; Cell Movement; Cell Proliferation; Cell Survival; Cells, Cultured; Cellulose; Centrosome; Ceratopogonidae; Chickens; Child; China; Cholera Toxin; Choline; Cholinesterases; Chromatography, High Pressure Liquid; Chromatography, Liquid; Chromatography, Micellar Electrokinetic Capillary; Chromatography, Reverse-Phase; Chronic Disease; Cinnamates; Cities; Citrates; Climate Change; Clinical Trials, Phase III as Topic; Coal; Coal Mining; Cohort Studies; Coinfection; Colchicine; Colony Count, Microbial; Colorectal Neoplasms; Coloring Agents; Common Cold; Complement Factor H; Computational Biology; Computer Simulation; Continuous Positive Airway Pressure; Contrast Media; Coordination Complexes; Coronary Artery Bypass; Coronavirus 3C Proteases; Coronavirus Infections; Coronavirus Protease Inhibitors; Corynebacterium glutamicum; Cosmetics; COVID-19; Creatinine; Cross-Sectional Studies; Crotonates; Crystallography, X-Ray; Cues; Culicidae; Culture Media; Curcuma; Cyclopentanes; Cyclopropanes; Cymbopogon; Cystine; Cytochrome P-450 CYP2B6; Cytochrome P-450 CYP2C19; Cytochrome P-450 CYP2C19 Inhibitors; Cytokines; Databases, Genetic; Death; Dendritic Cells; Density Functional Theory; Depsides; Diabetes Mellitus, Type 2; Diamond; Diarylheptanoids; Dibenzofurans; Dibenzofurans, Polychlorinated; Diclofenac; Diet; Dietary Carbohydrates; Dietary Supplements; Diffusion Magnetic Resonance Imaging; Dioxins; Diphenylamine; Disease Outbreaks; Disease Susceptibility; Disulfides; Dithiothreitol; Dizocilpine Maleate; DNA Methylation; DNA-Binding Proteins; DNA, Bacterial; Dogs; Dose-Response Relationship, Drug; Double-Blind Method; Doublecortin Protein; Drosophila melanogaster; Droughts; Drug Carriers; Drug Combinations; Drug Delivery Systems; Drug Liberation; Drug Resistance; Drug Resistance, Bacterial; Drug Resistance, Neoplasm; Drug Screening Assays, Antitumor; Dust; Dynactin Complex; Dysferlin; Echo-Planar Imaging; Echocardiography; Edaravone; Egypt; Elasticity; Electrodes; Electrolytes; Emodin; Emtricitabine; Endometriosis; Endothelium, Vascular; Endotoxins; Energy Metabolism; Energy Transfer; Enterobacteriaceae; Enterococcus faecalis; Enterotoxigenic Escherichia coli; Environmental Monitoring; Enzyme Inhibitors; Epidemiologic Factors; Epigenesis, Genetic; Erythrocytes; Escherichia coli; Escherichia coli Infections; Escherichia coli Vaccines; Esophageal Neoplasms; Esophagectomy; Esophagogastric Junction; Esterases; Esterification; Ethanol; Ethiopia; Ethnicity; Eucalyptus; Evidence-Based Practice; Exercise; Exercise Tolerance; Extracorporeal Membrane Oxygenation; Family; Fatty Acids; Feedback; Female; Ferric Compounds; Fibrin Fibrinogen Degradation Products; Filtration; Fish Diseases; Flavonoids; Flavonols; Fluorodeoxyglucose F18; Follow-Up Studies; Food Microbiology; Food Preservation; Forests; Fossils; Free Radical Scavengers; Freund's Adjuvant; Fruit; Fungi; Gallium; Gender Identity; Gene Expression Regulation; Gene Expression Regulation, Neoplastic; Gene Expression Regulation, Plant; Gene Knockdown Techniques; Genes, Bacterial; Genes, Plant; Genetic Predisposition to Disease; Genitalia; Genotype; Glomerulonephritis, IGA; Glottis; Glucocorticoids; Glucose; Glucuronides; Glutathione Transferase; Glycogen Synthase Kinase 3 beta; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Grassland; Guinea Pigs; Half-Life; Head Kidney; Heart Atria; Heart Rate; Heart Septum; HEK293 Cells; Hematopoietic Stem Cells; Hemodynamics; Hep G2 Cells; Hepacivirus; Hepatitis C; Hepatitis C, Chronic; Hepatocytes; Hesperidin; High-Frequency Ventilation; High-Temperature Requirement A Serine Peptidase 1; Hippocampus; Hirudins; History, 20th Century; History, 21st Century; HIV Infections; Homeostasis; Hominidae; Housing, Animal; Humans; Hydrocarbons, Brominated; Hydrogen Bonding; Hydrogen Peroxide; Hydrogen-Ion Concentration; Hydroxybutyrates; Hydroxyl Radical; Hypertension; Hypothyroidism; Image Interpretation, Computer-Assisted; Immunoconjugates; Immunogenic Cell Death; Indoles; Infant, Newborn; Infant, Premature; Infarction, Middle Cerebral Artery; Inflammation; Inflammation Mediators; Infrared Rays; Inhibitory Concentration 50; Injections, Intravenous; Interferon-gamma; Interleukin-23; Interleukin-4; Interleukin-6; Intermediate Filaments; Intermittent Claudication; Intestine, Small; Iridoid Glucosides; Iridoids; Iron; Isomerism; Isotope Labeling; Isoxazoles; Itraconazole; Kelch-Like ECH-Associated Protein 1; Ketoprofen; Kidney Failure, Chronic; Kinetics; Klebsiella pneumoniae; Lactams, Macrocyclic; Lactobacillus; Lactulose; Lakes; Lamivudine; Laparoscopy; Laparotomy; Laryngoscopy; Leucine; Limit of Detection; Linear Models; Lipid A; Lipopolysaccharides; Listeria monocytogenes; Liver; Liver Cirrhosis; Logistic Models; Longitudinal Studies; Losartan; Low Back Pain; Lung; Lupinus; Lupus Erythematosus, Systemic; Machine Learning; Macular Degeneration; Madin Darby Canine Kidney Cells; Magnetic Phenomena; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Magnetics; Malaria, Falciparum; Male; Mannans; MAP Kinase Signaling System; Mass Spectrometry; Melatonin; Membrane Glycoproteins; Membrane Proteins; Meniscectomy; Menisci, Tibial; Mephenytoin; Mesenchymal Stem Cells; Metal Nanoparticles; Metal-Organic Frameworks; Methionine; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Nude; Mice, Obese; Mice, Transgenic; Microbial Sensitivity Tests; Microcirculation; MicroRNAs; Microscopy, Video; Microtubules; Microvascular Density; Microwaves; Middle Aged; Minimally Invasive Surgical Procedures; Models, Animal; Models, Biological; Models, Molecular; Models, Theoretical; Molecular Docking Simulation; Molecular Structure; Molecular Weight; Morus; Mouth Floor; Multicenter Studies as Topic; Multiple Sclerosis; Multiple Sclerosis, Relapsing-Remitting; Muscle, Skeletal; Myocardial Ischemia; Myocardium; NAD; NADP; Nanocomposites; Nanoparticles; Naphthols; Nasal Lavage Fluid; Nasal Mucosa; Neisseria meningitidis; Neoadjuvant Therapy; Neoplasm Invasiveness; Neoplasm Recurrence, Local; Neoplasms, Experimental; Neural Stem Cells; Neuroblastoma; Neurofilament Proteins; Neurogenesis; Neurons; New York; NF-E2-Related Factor 2; NF-kappa B; Nicotine; Nitriles; Nitrogen; Nitrogen Fixation; North America; Observer Variation; Occupational Exposure; Ochrobactrum; Oils, Volatile; Olea; Oligosaccharides; Omeprazole; Open Field Test; Optimism; Oregon; Oryzias; Osmolar Concentration; Osteoarthritis; Osteoblasts; Osteogenesis; Ovarian Neoplasms; Ovariectomy; Oxadiazoles; Oxidation-Reduction; Oxidative Stress; Oxygen; Ozone; p38 Mitogen-Activated Protein Kinases; Pakistan; Pandemics; Particle Size; Particulate Matter; Patient-Centered Care; Pelargonium; Peptides; Perception; Peripheral Arterial Disease; Peroxides; Pets; Pharmaceutical Preparations; Pharmacogenetics; Phenobarbital; Phenols; Phenotype; Phosphates; Phosphatidylethanolamines; Phosphines; Phospholipids; Phosphorus; Phosphorylation; Photoacoustic Techniques; Photochemotherapy; Photosensitizing Agents; Phylogeny; Phytoestrogens; Pilot Projects; Plant Components, Aerial; Plant Extracts; Plant Immunity; Plant Leaves; Plant Oils; Plants, Medicinal; Plasmodium berghei; Plasmodium falciparum; Platelet Activation; Platelet Function Tests; Pneumonia, Viral; Poaceae; Pogostemon; Poloxamer; Poly I; Poly(ADP-ribose) Polymerase Inhibitors; Polychlorinated Biphenyls; Polychlorinated Dibenzodioxins; Polycyclic Compounds; Polyethylene Glycols; Polylysine; Polymorphism, Genetic; Polymorphism, Single Nucleotide; Population Dynamics; Portasystemic Shunt, Transjugular Intrahepatic; Positron Emission Tomography Computed Tomography; Postoperative Complications; Postprandial Period; Potassium Cyanide; Predictive Value of Tests; Prefrontal Cortex; Pregnancy; Prepulse Inhibition; Prevalence; Procalcitonin; Prodrugs; Prognosis; Progression-Free Survival; Proline; Proof of Concept Study; Prospective Studies; Protein Binding; Protein Conformation; Protein Domains; Protein Folding; Protein Multimerization; Protein Sorting Signals; Protein Structure, Secondary; Proton Pump Inhibitors; Protozoan Proteins; Psychometrics; Pulse Wave Analysis; Pyridines; Pyrrolidines; Quality of Life; Quantum Dots; Quinoxalines; Quorum Sensing; Radiopharmaceuticals; Rain; Random Allocation; Randomized Controlled Trials as Topic; Rats; Rats, Sprague-Dawley; Rats, Wistar; RAW 264.7 Cells; Reactive Oxygen Species; Receptor, Angiotensin, Type 1; Receptor, PAR-1; Receptors, CXCR4; Receptors, Estrogen; Receptors, Glucocorticoid; Receptors, Interleukin-1; Receptors, Interleukin-17; Receptors, Notch; Recombinant Fusion Proteins; Recombinant Proteins; Reducing Agents; Reflex, Startle; Regional Blood Flow; Regression Analysis; Reperfusion Injury; Reproducibility of Results; Republic of Korea; Respiratory Tract Diseases; Retrospective Studies; Reverse Transcriptase Inhibitors; Rhinitis, Allergic; Risk Assessment; Risk Factors; Rituximab; RNA, Messenger; RNA, Ribosomal, 16S; ROC Curve; Rosmarinic Acid; Running; Ruthenium; Rutin; Sarcolemma; Sarcoma; Sarcopenia; Sarcoplasmic Reticulum; SARS-CoV-2; Scavenger Receptors, Class A; Schools; Seasons; Seeds; Sequence Analysis, DNA; Severity of Illness Index; Sex Factors; Shock, Cardiogenic; Short Chain Dehydrogenase-Reductases; Signal Transduction; Silver; Singlet Oxygen; Sinusitis; Skin; Skin Absorption; Small Molecule Libraries; Smoke; Socioeconomic Factors; Soil; Soil Microbiology; Solid Phase Extraction; Solubility; Solvents; Spain; Spectrometry, Mass, Electrospray Ionization; Spectroscopy, Fourier Transform Infrared; Speech; Speech Perception; Spindle Poles; Spleen; Sporothrix; Staphylococcal Infections; Staphylococcus aureus; Stereoisomerism; Stomach Neoplasms; Stress, Physiological; Stroke Volume; Structure-Activity Relationship; Substrate Specificity; Sulfonamides; Surface Properties; Surface-Active Agents; Surveys and Questionnaires; Survival Rate; T-Lymphocytes, Cytotoxic; Tandem Mass Spectrometry; Temperature; Tenofovir; Terpenes; Tetracycline; Tetrapleura; Textiles; Thermodynamics; Thiobarbituric Acid Reactive Substances; Thrombin; Thyroid Hormones; Thyroid Neoplasms; Tibial Meniscus Injuries; Time Factors; Tissue Distribution; Titanium; Toluidines; Tomography, X-Ray Computed; Tooth; Tramadol; Transcription Factor AP-1; Transcription, Genetic; Transfection; Transgender Persons; Translations; Treatment Outcome; Triglycerides; Ubiquinone; Ubiquitin-Specific Proteases; United Kingdom; United States; Up-Regulation; Vascular Stiffness; Veins; Ventricular Remodeling; Viral Load; Virulence Factors; Virus Replication; Vitis; Voice; Voice Quality; Wastewater; Water; Water Pollutants, Chemical; Water-Electrolyte Balance; Weather; Wildfires; Wnt Signaling Pathway; Wound Healing; X-Ray Diffraction; Xenograft Model Antitumor Assays; Young Adult; Zoogloea

Neuroprotective effects of curcumin have been shown in previous studies. This updated systematic review of clinical trials aimed to investigate the effect of curcumin on neurological disorders. Databases including PubMed, Scopus, Web of Science, and Google Scholar were systematically searched to identify clinical trials investigating the effects of curcumin/turmeric supplements alone, or in combination with other ingredients, on neurological diseases. Nineteen studies comprising 1,130 patients met the inclusion criteria. Generally, intervention and study outcomes were heterogeneous. In most of the studies, curcumin had a favorable effect on oxidative stress and inflammation. However, with the exception of AD, curcumin supplementation either alone, or in combination with other ingredients, had beneficial effects on clinical outcomes for the other aforementioned neurodegenerative diseases. For example, the frequency, severity, and duration of migraine attacks, scores on the revised ALS functional rating scale, and the occurrence of motor complications in PD were all significantly improved with curcumin supplementation either alone or in combination with other ingredients. However, in three studies, several adverse side effects (mostly gastrointestinal in nature) were reported. Curcumin supplementation may have favorable effects on inflammatory status and clinical outcomes of patients with neurological disease, although the results were not consistent.

Topics: Curcuma; Curcumin; Dietary Supplements; Humans; Inflammation; Migraine Disorders

Exhaustive and acute unusual physical exercise leads to muscle damage. Curcumin has been widely studied due to the variety of its biological activities, attributed to its antioxidant and anti-inflammatory properties. Furthermore, it has shown positive effects on physical exercise practitioners. However, there is no literature consensus on the beneficial effects of curcumin in acute physical activities performed by sedentary individuals. Therefore, we systematically reviewed evidence from clinical trials on the main effects of curcumin supplementation on inflammatory markers, sports performance, and muscle damage during acute physical exercises in these individuals. We searched PubMed/MEDLINE, Scopus, Web of Science, and Embase databases, and only original studies were analyzed according to the PRISMA guidelines. The included studies were limited to supplementation of curcumin during acute exercise. A total of 5 studies were selected. Methodological quality assessments were examined using the SYRCLE's risk-of-bias tool. Most studies have shown positive effects of curcumin supplementation in sedentary individuals undergoing acute physical exercise. Overall, participants supplemented with curcumin showed less muscle damage, reduced inflammation, and better muscle performance. The studies showed heterogeneous data and exhibited methodological limitations; therefore, further research is necessary to ensure curcumin supplementation benefits during acute and high-intensity physical exercises. Additionally, mechanistic and highly controlled studies are required to improve the quality of the evidence and to elucidate other possible mechanisms. This study is registered with Prospero number CRD42021262718.

Topics: Adult; Anti-Inflammatory Agents, Non-Steroidal; Athletic Performance; Curcumin; Dietary Supplements; Exercise; Female; Humans; Inflammation; Male; Muscle, Skeletal; Sedentary Behavior; Young Adult

Curcumin is a natural compound with great potential for disease treatment. A large number of studies have proved that curcumin has a variety of biological activities, among which anti-inflammatory effect is a significant feature of it. Inflammation is a complex and pervasive physiological and pathological process. The physiological and pathological mechanisms of inflammatory bowel disease, psoriasis, atherosclerosis, COVID-19 and other research focus diseases are not clear yet, and they are considered to be related to inflammation. The anti-inflammatory effect of curcumin can effectively improve the symptoms of these diseases and is expected to be a candidate drug for the treatment of related diseases. This paper mainly reviews the anti-inflammatory effect of curcumin, the inflammatory pathological mechanism of related diseases, the regulatory effect of curcumin on these, and the latest research results on the improvement of curcumin pharmacokinetics. It is beneficial to the further study of curcumin and provides new ideas and insights for the development of curcumin anti-inflammatory preparations.

Topics: Animals; Anti-Inflammatory Agents; Atherosclerosis; COVID-19 Drug Treatment; Curcumin; Depression; Humans; Inflammation; SARS-CoV-2

Oxidative stress and inflammation remain the major complications implicated in the development and progression of metabolic complications, including obesity, type 2 diabetes (T2D) and nonalcoholic fatty liver disease (NAFLD). In fact, due to their abundant antioxidant and anti-inflammatory properties, there is a general interest in understanding the therapeutic effects of some major food-derived bioactive compounds like curcumin against diverse metabolic diseases. Hence, a systematic search, through prominent online databases such as MEDLINE, Scopus, and Google Scholar was done focusing on randomized controlled trials (RCTs) reporting on the impact of curcumin supplementation in individuals with diverse metabolic complications, including obesity, T2D and NAFLD. Summarized findings suggest that curcumin supplementation can significantly reduce blood glucose and triglycerides levels, including markers of liver function like alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in patients with T2D and NAFLD. Importantly, this effect was consistent with the reduction of predominant markers of oxidative stress and inflammation, such as the levels of malonaldehyde (MDA), tumor necrosis factor-alpha (TNF-α), high sensitivity C-reactive protein (hs-CRP) and monocyte chemoattractant protein-1 (MCP-1) in these patients. Although RCTs suggest that curcumin is beneficial in ameliorating some metabolic complications, future research is still necessary to enhance its absorption and bioavailability profile, while also optimizing the most effective therapeutic doses.

Topics: Antioxidants; Biomarkers; Curcumin; Diabetes Mellitus, Type 2; Dietary Supplements; Functional Food; Humans; Inflammation; Non-alcoholic Fatty Liver Disease; Obesity; Oxidative Stress

Obesity remains a pervasive health concern worldwide with concomitant comorbidities such as cardiovascular diseases, diabetes, inflammation, and other metabolic disorders. A wealth of data validates dietary and lifestyle modifications such as restricting caloric intake and increasing physical activity to slow the obesity development. Recently, the advent of phytochemicals such as curcumin, the active ingredient in turmeric, has attracted considerable research interest in tracking down their possible effects in protection against obesity and obesity-related comorbidities. According to the existing literature, curcumin may regulate lipid metabolism and suppress chronic inflammation interacting with white adipose tissue, which plays a central role in the complications associated with obesity. Curcumin also inhibits the differentiation of adipocyte and improves antioxidant properties. In the present review, we sought to deliberate the possible effects of curcumin in downregulating obesity and curtailing the adverse health effects of obesity.

Topics: Adipocytes; Adipose Tissue, White; Curcumin; Humans; Inflammation; Obesity

Curcumin is a major active principle of Curcuma longa. There are more than 1700 citations in the Medline, reflecting various biological effects of curcumin. Most of these biological activities are associated with the antioxidant, anti-inflammatory and antitumor activity of the molecule. Several reports suggest various targets of natural curcumin that include growth factors, growth factor receptor, cytokines, enzymes and gene regulators of apoptosis. This review focuses on the improved curcumin derivatives that target the cancer and inflammation.. In this present review, we explored the anticancer drugs with curcumin-based drugs under pre-clinical and clinical studies with critical examination. Based on the strong scientific reports of patentable and non-patented literature survey, we have investigated the mode of the interactions of curcumin-based molecules with the target molecules.. Advanced studies have added new dimensions of the molecular response of cancer cells to curcumin at the genomic level. However, poor bioavailability of the molecule seems to be the major limitation of the curcumin. Several researchers have been involved to improve the curcumin derivatives to overcome this limitation. Sufficient data of clinical trials to various cancers that include multiple myeloma, pancreatic cancer and colon cancer, have also been discussed.. The detailed analysis of the structure-activity relationship (SAR) and common synthesis of curcumin-based derivatives have been discussed in the review. Utilising the predictions of in silico coupled with validation reports of in vitro and in vivo studies have concluded many targets for curcumin. Among them, cancer-related inflammation genes regulating curcumin-based molecules are a very promising target to overcome hurdles in the multimodality therapy of cancer.

Topics: Anti-Inflammatory Agents; Antineoplastic Agents; Curcumin; Drug Design; Humans; Inflammation; Neoplasms

Pain is an unpleasant sensation that has complex and varying causative etiology. Modern drug discovery focuses on identifying potential molecules that target multiple pathways with a safer profile compared to those with a single target. The current treatment of pain and inflammation with the available therapeutics has a number of major side effects. Pain is one of the major clinical problems that need functional therapeutics which act on multiple targets and with low toxicity. Curcumin, a naturally occurring polyphenolic compound from Curcuma longa, has been used for years in Ayurvedic, Chinese, and in many other systems of traditional medicine. Pre-clinical data published thus far demonstrated that curcumin possesses multi-target biological functions, suggesting its potential use to cure different diseases. However, there is no or very brief systematic review of its potential use in pain and inflammation with underlying mechanisms for such activities. Accordingly, the aim of the current review was to update the pre-clinical data of curcumin and its multiple targeting pathways for analgesic and anti-inflammatory effects, and to further propose a molecular mechanism(s). A literature study was conducted using different known databases, including Pubmed, SciFinder, Google Scholar, and Science Direct. Available pre-clinical data suggest the ameliorating effect of curcumin in pain and inflammation is rendered through the modulation of pain pathways, including inhibition of a number of pro-inflammatory mediators, inhibition of oxidative stress and cyclooxygenase-2 (COX-2), down-regulation of Ca2+/calmodulin-depend protein kinase II (CaMKIIα) and calcium channels like transient receptor potential (TRP), modulation of metabotropic glutamate receptor-2 (mGlu2), modulation of monoamine system, inhibition of JAK2/STAT3 signaling pathway, remodeling of extracellular matrix proteins, inhibition of apoptosis, inhibition of JNK/MAPK and ERK/CREB signaling pathway, and activation of the opioid system. Taken all together, it is evident that curcumin is one of the promising, safe, and natural polyphenolic molecules that target multiple molecular pathways in pain and can be beneficial in the treatment and management of pain and inflammation.

Topics: Apoptosis; Curcumin; Humans; Inflammation; Pain; Signal Transduction

Curcumin is the effective ingredient of turmeric, sometimes used as a painkiller in traditional medicine. It has extensive biological properties such as anti-inflammatory and antioxidant activities. SARS-CoV-2 is a betacoronavirus developing severe pneumonitis. Inflammasome is one of the most important components of innate immunity, which exacerbates inflammation by increasing IL-1β and IL-18 production. Studies on viral infections have shown overactivity of inflammasome and thus the occurrence of destructive and systemic inflammation in patients. NLRP3 inflammasome has been shown to play a key role in the pathogenesis of viral diseases. The proliferation of SARS-CoV-2 in a wide range of cells can be combined with numerous observations of direct and indirect activation of inflammasome by other coronaviruses. Activation of the inflammasome is likely to be involved in the formation of cytokine storm. Curcumin regulates several molecules in the intracellular signal transduction pathways involved in inflammation, including IBB, NF-kBERK1,2, AP-1, TGF-β, TXNIP, STAT3, PPARγ, JAK2-STAT3, NLRP3, p38MAPK, Nrf2, Notch-1, AMPK, TLR-4 and MyD-88. Due to anti-inflammatory and anti-inflammasome properties without any special side effects, curcumin can potentially play a role in the treatment of COVID-19 infection along with other drug regimens.

Topics: Anti-Inflammatory Agents, Non-Steroidal; COVID-19; COVID-19 Drug Treatment; Curcumin; Humans; Inflammation; NLR Family, Pyrin Domain-Containing 3 Protein; SARS-CoV-2

Due to lack of approved drugs and vaccines, the medical world has resorted to older drugs, produced for viral infections and other diseases, as a remedy to combat COVID-19. The accumulating evidence from in vitro and in vivo studies for SARS-CoV and MERS-CoV have demonstrated that several polyphenols found in plants and zinc- polyphenol clusters have been in use as herbal medicines have antiviral activities against viruses with various mechanisms.. Curcumin, zinc and zinc-ionophores have been considered as nutraceuticals and nutrients showing great antiviral activities with their medicinal like activities.. In this work, we discussed the potential prophylactic and/or therapeutic effects of curcumin, zinc and zinc-ionophores in treatment of viral infections including COVID-19.. Curcuminoids and Zinc classified as nutraceuticals under GRAS (Generally Recognized As Safe) by FDA can provide complementary treatment for COVID 19 patients with their immunity-boosting and antiviral properties.

Topics: Antiviral Agents; COVID-19; Curcumin; Cytokine Release Syndrome; Dietary Supplements; Food; Humans; Inflammation; Ionophores; Pandemics; Plant Extracts; Plant Preparations; Polyphenols; Trace Elements; Virus Replication; Zinc

Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear receptor superfamily that regulate the expression of genes related to lipid and glucose metabolism and inflammation. There are three members: PPARα, PPARβ or PPARγ. PPARγ have several ligands. The natural agonists are omega 9, curcumin, eicosanoids and others. Among the synthetic ligands, we highlight the thiazolidinediones, clinically used as an antidiabetic. Many of these studies involve natural or synthetic products in different pathologies. The mechanisms that regulate PPARγ involve post-translational modifications, such as phosphorylation, sumoylation and ubiquitination, among others. It is known that anti-inflammatory mechanisms involve the inhibition of other transcription factors, such as nuclear factor kB(NFκB), signal transducer and activator of transcription (STAT) or activator protein 1 (AP-1), or intracellular signaling proteins such as mitogen-activated protein (MAP) kinases. PPARγ transrepresses other transcription factors and consequently inhibits gene expression of inflammatory mediators, known as biomarkers for morbidity and mortality, leading to control of the exacerbated inflammation that occurs, for instance, in lung injury/acute respiratory distress. Many studies have shown the therapeutic potentials of PPARγ on pulmonary diseases. Herein, we describe activities of the PPARγ as a modulator of inflammation, focusing on lung injury and including definition and mechanisms of regulation, biological effects and molecular targets, and its role in lung diseases caused by inflammatory stimuli, bacteria and virus, and molecular-based therapy.

Topics: Animals; Curcumin; Eicosanoids; Humans; Inflammation; Ligands; Lung Diseases; PPAR gamma; Protein Processing, Post-Translational; Signal Transduction

The consumption of exogenous antioxidants isolated from herbal extracts has shown beneficial effects on ameliorating dialysis-related complications through debilitating oxidative stress and inflammatory process. Many clinical studies available in public databases have reported the improved consequences of dialysis in patients supplemented with herbal antioxidants. Exploration of such data offers great possibilities for gaining insights into the potential mechanisms and medical implications of herbal antioxidants. In this work, the mechanisms and implications of some famous bioactive substances including silymarin, curcumin, resveratrol, emodin, and quercetin on the consequences of dialysis in chronic kidney disease (CKD) patients were explored. The protective features of silymarin are due to the flavonoid complex silybin. Curcumin is an active element from the root of curcuma longa with extensive beneficial properties, including antioxidant, anti-inflammatory activity, and inhibitory effects on cell apoptosis. Resveratrol can reduce the oxidative stress by neutralization of free radicals. Emodin is known as a natural anthraquinone derivative isolated from Chinese herbs. Finally, quercetin has been reported to exhibit several properties including antioxidant, anti-diabetic, analgesic, antihistaminic, antiviral, cholesterol reducer, and renal hemodynamic modulator. However, potential mechanisms and medical implications of the aforementioned herbal antioxidants seem to be more complicated, that is, more studies are required in this field.

Topics: Antioxidants; Cardiovascular Diseases; Curcumin; Emodin; Humans; Inflammation; Oxidative Stress; Plant Extracts; Quercetin; Renal Dialysis; Renal Insufficiency, Chronic; Resveratrol; Silymarin

The high incidence of obesity is associated with an increasing risk of several chronic diseases such as cardiovascular disease, type 2 diabetes and non-alcoholic fatty liver disease (NAFLD). Sustained obesity is characterized by a chronic and unsolved inflammation of adipose tissue, which leads to a greater expression of proinflammatory adipokines, excessive lipid storage and adipogenesis. The purpose of this review is to clarify how inflammatory mediators act during adipose tissue dysfunction in the development of insulin resistance and all obesity-associated diseases. In particular, we focused our attention on the role of inflammatory signaling in brown adipose tissue (BAT) thermogenic activity and the browning of white adipose tissue (WAT), which represent a relevant component of adipose alterations during obesity. Furthermore, we reported the most recent evidence in the literature on nutraceutical supplementation in the management of the adipose inflammatory state, and in particular on their potential effect on common inflammatory mediators and pathways, responsible for WAT and BAT dysfunction. Although further research is needed to demonstrate that targeting pro-inflammatory mediators improves adipose tissue dysfunction and activates thermogenesis in BAT and WAT browning during obesity, polyphenols supplementation could represent an innovative therapeutic strategy to prevent progression of obesity and obesity-related metabolic diseases.

Topics: Adipogenesis; Adipose Tissue; Adipose Tissue, Brown; Adipose Tissue, White; Animals; Curcumin; Diet; Dietary Supplements; Endoplasmic Reticulum; Fatty Acids, Unsaturated; Humans; Inflammation; Insulin Resistance; Intestines; Lipids; Macrophages; Obesity; Polyphenols; Resveratrol; Signal Transduction; Thermogenesis

Curcumin is a lipophilic polyphenol, isolated from the plant turmeric of Curcuma longa. Curcuma longa has always been used in traditional medicine in Asian countries because it is believed to have numerous health benefits. Nowadays it is widely used as spice component and in emerging nutraceutical food worldwide. Numerous studies have shown that curcumin possesses, among others, potential anti-inflammatory properties. Obesity represents a main risk factor for several chronic diseases, including type 2 diabetes, cardiovascular disease, and some types of cancer. The establishment of a low-grade chronic inflammation, both systemically and locally in adipose tissue, occurring in obesity most likely represents a main factor in the pathogenesis of chronic diseases. The molecular mechanisms responsible for the onset of the obesity-associated inflammation are different from those involved in the classic inflammatory response caused by infections and involves different signaling pathways. The inflammatory process in obese people is triggered by an inadequate intake of nutrients that produces quantitative and qualitative alterations of adipose tissue lipid content, as well as of various molecules that act as endogenous ligands to activate immune cells. In particular, dysfunctional adipocytes secrete inflammatory cytokines and chemokines, the adipocytokines, able to recruit immune cells into adipose tissue, amplifying the inflammatory response also at systemic level. This review summarizes the most recent studies focused at elucidating the molecular targets of curcumin activity responsible for its anti-inflammatory properties in obesity-associated inflammation and related pathologies.

Topics: Anti-Inflammatory Agents; Curcumin; Humans; Inflammation; Obesity

Different modalities of treatments are available for management of gingival disease but most have adverse effects. Curcumin has anti-inflammatory properties and can be used for management of various inflammatory processes. This systematic review evaluates the effects of curcumin as an adjuvant to oral hygiene on plaque index (PI), gingival index (GI), gingival bleeding index (GBI), and inflammation in patients with gingivitis. A comprehensive search was conducted using PubMed/MEDLINE, Cochrane, SCOPUS, and Google Scholar. Based on the Population, Intervention, Control, and Outcome (PICO) model, clinical trials which tested the effects of curcumin as an adjunctive product or alone in control of gingival inflammation up until 21 February 2020 with language restrictions were selected. From the 422 papers found, 14 met the eligibility criteria. In most of these studies, curcumin treatment achieved significant reductions in PI, GI, GBI, and microbial colony count and was as effective as chlorhexidine mouthwash, with no serious adverse effects. We conclude that treatment with curcumin for gingivitis is safe as a natural herbal compound and is as effective as chlorhexidine mouthwash.

Topics: Chlorhexidine; Curcumin; Gingivitis; Humans; Inflammation; Mouthwashes

Prostate cancer is one of the significant causes of morbidity and mortality worldwide. Benign prostatic hyperplasia is another condition of the prostate which, like prostate cancer, is more common among ageing men and is linked to inflammation. In this study, a systematic review was undertaken to estimate the effect of turmeric or curcumin supplementation on prostate diseases. A comprehensive search was conducted in PubMed, Scopus, ISI Web of Science and Google Scholar up to 15 April 2020 to identify clinical trials assessing the effects of curcumin/turmeric alone or in combination with other herbs on prostate diseases. This led to the identification of 11 records comprising 745 patients who met the eligibility criteria. Eight studies were conducted on patients with prostate cancer, and three were on other diseases of the prostate. Although outcomes across the studies were heterogeneous, in some studies curcumin/turmeric supplementation had some favourable effects. This included beneficial effects on the levels of prostate-specific antigen (PSA) (2/6 studies), quality of life (1/2 studies), as well as on oxidative stress markers, feelings of incomplete bladder emptying, urination frequency, intermittency, urgency, weak stream, straining and nocturia. Curcumin/turmeric supplementation had no significant adverse effects among patients. This study demonstrated that turmeric or curcumin supplementation might have beneficial effects on some parameters related to prostate diseases, but it should be noted that some studies showed no effect. Therefore, further studies using curcumin-related compounds, particularly in highly bioavailable forms, are needed to assess the impact of curcumin on prostate conditions.

Topics: Curcuma; Curcumin; Humans; Inflammation; Male; Prostate; Quality of Life

Due to the global increase in lifespan, the proportion of people showing cognitive impairment is expected to grow exponentially. As target-specific drugs capable of tackling dementia are lagging behind, the focus of preclinical and clinical research has recently shifted towards natural products. Curcumin, one of the best investigated botanical constituents in the biomedical literature, has been receiving increased interest due to its unique molecular structure, which targets inflammatory and antioxidant pathways. These pathways have been shown to be critical for neurodegenerative disorders such as Alzheimer's disease and more in general for cognitive decline. Despite the substantial preclinical literature on the potential biomedical effects of curcumin, its relatively low bioavailability, poor water solubility and rapid metabolism/excretion have hampered clinical trials, resulting in mixed and inconclusive findings. In this review, we highlight current knowledge on the potential effects of this natural compound on cognition. Furthermore, we focus on new strategies to overcome current limitations in its use and improve its efficacy, with attention also on gender-driven differences.

Topics: Anti-Inflammatory Agents; Cognitive Dysfunction; Curcuma; Glucose; Homeostasis; Humans; Inflammation

The peroxisome proliferator-activated receptor (PPAR) β/δ has an important role in multiple inflammatory conditions, including obesity, hypertension, cancer, cardiovascular disease, diabetes mellitus, and autoimmune diseases. PPARβ/δ forms a heterodimer with the retinoic acid receptor and binds to peroxisome proliferator response elements to initiate transcription of its target genes. PPARβ/δ is also able to suppress the activities of several transcription factors, including nuclear factor κB, and activator protein 1, thus regulating anti-inflammatory cellular responses and playing a protective role in several diseases. Recent studies have shown that nutritional compounds, including nutrients and bioactive compounds, can regulate PPARβ/δ expression. This review discusses key nutritional compounds that are known to modulate PPARβ/δ and are likely to affect human health.

Topics: Animals; Curcumin; Diet; Flavonoids; Humans; Inflammation; NF-kappa B; Phytochemicals; Polyphenols; PPAR delta; PPAR-beta; Receptors, Retinoic Acid; Vitamin A

Topics: Angiogenesis Inhibitors; Anti-Inflammatory Agents; Collagenases; Curcumin; Cytokines; Hemophilia A; Humans; Inflammation; Iron; Joint Diseases; Neovascularization, Pathologic; Oxidative Stress

Colorectal cancer (CRC) is associated with significant morbidity and mortality in the US and worldwide. CRC is the second most common cancer-related death in both men and women globally. Chronic inflammation has been identified as one of the major risk factors of CRC. It may drive genetic and epigenetic/epigenomic alterations, such as DNA methylation, histone modification, and non-coding RNA regulation. Current prevention modalities for CRC are limited and some treatment regimens such as use the nonsteroidal anti-inflammatory drug aspirin may have severe side effects, namely gastrointestinal ulceration and bleeding. Therefore, there is an urgent need of developing alternative strategies. Recently, increasing evidence suggests that several dietary cancer chemopreventive phytochemicals possess anti-inflammation and antioxidative stress activities, and may prevent cancers including CRC. Curcumin (CUR) is the yellow pigment that is found in the rhizomes of turmeric (Curcuma longa). Many studies have demonstrated that CUR exhibit strong anticancer, antioxidative stress, and anti-inflammatory activities by regulating signaling pathways, such as nuclear factor erythroid-2-related factor 2, nuclear factor-κB, and epigenetics/epigenomics pathways of histones modifications, and DNA methylation. In this review, we will discuss the latest evidence in epigenetics/epigenomics alterations by CUR in CRC and their potential contribution in the prevention of CRC.

Topics: Antineoplastic Agents; Colonic Neoplasms; Curcuma; Curcumin; Epigenesis, Genetic; Epigenomics; Humans; Inflammation; Neoplasm Staging; Phytotherapy

Atherosclerosis is a complex and long-lasting disorder characterized by chronic inflammation of arteries that leads to the initiation and progression of lipid-rich plaques, in which monocytes/macrophages play the central role in endothelial inflammation and taking up these lipids. Circulating monocytes can adopt a long-term proinflammatory phenotype leading to their atherogenic activities. During atherogenic condition, inflammatory monocytes adhere to the surface of the activated endothelial cells and then transmigrate across the endothelial monolayer into the intima, where they proliferate and differentiate into macrophages and take up the lipoproteins, forming foam cells that derive atherosclerosis progression. Therefore, modulating the atherogenic activities of inflammatory monocytes can provide a valuable therapeutic approach for atherosclerosis prevention and treatment. Curcumin is a naturally occurring polyphenolic compound with numerous pharmacological activities and shows protective effects against atherosclerosis; however, underlying mechanisms are not clearly known yet. In the present review, on the basis of a growing body of evidence, we show that curcumin can exert antiatherosclerotic effect through inhibiting the atherogenic properties of monocytes, including inflammatory cytokine production, adhesion, and transendothelial migration, as well as intracellular cholesterol accumulation.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Atherosclerosis; Curcumin; Disease Models, Animal; Humans; In Vitro Techniques; Inflammation; Monocytes; Rats

Topics: Animals; Aortic Diseases; Atherosclerosis; Biomarkers; Curcumin; Inflammation; Mice

Endometriosis is one of the main common gynecological disorders, which is characterized by the presence of glands and stroma outside the uterine cavity. Some findings have highlighted the main role of inflammation in endometriosis by acting on proliferation, apoptosis and angiogenesis. Oxidative stress, an imbalance between reactive oxygen species and antioxidants, could have a key role in the initiation and progression of endometriosis by resulting in inflammatory responses in the peritoneal cavity. Nevertheless, the mechanisms underlying this disease are still unclear and therapies are not currently efficient. Curcumin is a major anti-inflammatory agent. Several findings have highlighted the anti-oxidant, anti-inflammatory and anti-angiogenic properties of curcumin. The purpose of this review is to summarize the potential action of curcumin in endometriosis by acting on inflammation, oxidative stress, invasion and adhesion, apoptosis and angiogenesis.

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Apoptosis; Curcumin; Endometriosis; Female; Humans; Inflammation; Oxidative Stress; Peritoneal Cavity; Reactive Oxygen Species

Periodontal disease is one of the most common causes of tooth loss among adults. Research shows that inflammation is one of the crucial components in the initiation and progression of periodontitis. Various herbal medicines have recently been receiving attention for the management of periodontitis owing to their general safety and efficacy. Curcumin, a bioactive polyphenol extracted from Curcuma longa, has been shown to possess antioxidant, antimicrobial, anti-inflammatory and analgesic properties. Several studies have assessed the efficacy of curcumin against periodontal diseases. These studies have shown equivalent or even higher efficacy of curcumin compared to the commonly used medications for the management of periodontitis such as chlorhexidine. Herein, we review the experimental and clinical findings on the anti-periodontitis effects of curcumin and the pharmacological mechanisms underlying these effects.

Topics: Adult; Anti-Inflammatory Agents; Chlorhexidine; Curcumin; Humans; Inflammation; Periodontal Diseases; Periodontitis

Curcumin is the major bioactive polyphenolic ingredient of turmeric. Increasing evidence indicates that the health benefits of curcumin are mediated through its anti-inflammatory and antioxidant effects. Inflammasomes are essential components of inflammatory pathways that activate caspase-1 leading to pyroptosis and stimulate maturation and secretion of the proinflammatory cytokines, interleukin-1β (IL-1β) and interleukin-18 (IL-18) through nuclear factor kappa-B (NF-κB) signaling. The current review outlines the mechanisms of curcumin as an inflammasome modulator in inflammatory-related diseases. Regulation of NF-κB signaling and interleukins secretion is the most prominent functional mechanism of curcumin in modulating inflammasomes. More importantly, curcumin can exert its anti-inflammatory role mainly through the down-regulation of NLRP3 inflammasomes. Given the fundamental role of inflammation in diseases, such as arthritis, cancer and cardiorenal disease, curcumin may have a pivotal therapeutic role through its ability to produce beneficial anti-inflammatory effects.

Topics: Animals; Anti-Inflammatory Agents; Curcumin; Cytokines; Humans; Inflammasomes; Inflammation; Inflammation Mediators; NF-kappa B; NLR Family, Pyrin Domain-Containing 3 Protein; Signal Transduction

Topics: Animals; Benzoquinones; Biological Products; Biomimetics; Caffeic Acids; Curcumin; Cytokines; Exosomes; Humans; Inflammation; Inflammatory Bowel Diseases; Insecta; Macromolecular Substances; Nanomedicine; Oxidative Stress; Phenylethyl Alcohol; Phytochemicals; Plant Extracts; Polysaccharides; Quercetin; Resveratrol; Stilbenes; Transcription Factors; Translational Research, Biomedical; Vasoactive Intestinal Peptide; Zingiber officinale

The NLRP3 inflammasome formation and following cytokine secretion is a crucial step in innate immune responses. Internal and external factors may trigger inflammasome activation and result in inflammatory cytokine secretion. Inflammasome formation and activity play critical roles in several disease pathologies such as cardiovascular, metabolic, renal, digestive, and CNS diseases. Underlying pathways are not yet clear, but phytochemicals as alternative therapies have been extensively used for suppression of inflammatory responses.. In this review, we aimed to summarize in vivo and in vitro effects on NLRP3 inflammasome activation of selected phytochemicals.. Three phytochemicals; Sulforaphane, Curcumin, and Resveratrol were selected, and studies were reviewed to clarify their intracellular signaling mechanism in NLRP3 inflammasome activity. PubMed and Scopus databases are used for the search. For sulforaphane, 8 articles, for curcumin, 25 articles, and for resveratrol, 41 articles were included in the review.. In vitro and in vivo studies pointed out that the selected phytochemicals have inhibitory properties on NLRP3 inflammasome activity. However, neither the mechanism is clear, nor the study designs and doses are standardized.

Topics: Animals; Cardiovascular Diseases; Central Nervous System Diseases; Curcumin; Humans; Inflammasomes; Inflammation; Isothiocyanates; NLR Family, Pyrin Domain-Containing 3 Protein; Phytochemicals; Resveratrol; Signal Transduction; Sulfoxides

Curcumin is herbal compound that has been shown to have anti-cancer effects in pre-clinical and clinical studies. The anti-cancer effects of curcumin include inhibiting the carcinogenesis, inhibiting angiogenesis, and inhibiting tumour growth. This study aims to determine the Clinical effects of curcumin in different types of cancers using systematic review approach.. A systematic review methodology is adopted for undertaking detailed analysis of the effects of curcumin in cancer therapy. The results presented in this paper is an outcome of extracting the findings of the studies selected from the articles published in international databases including SID, MagIran, IranMedex, IranDoc, Google Scholar, ScienceDirect, Scopus, PubMed and Web of Science (ISI). These databases were thoroughly searched, and the relevant publications were selected based on the plausible keywords, in accordance with the study aims, as follows: prevalence, curcumin, clinical features, cancer.. The results are derived based on several clinical studies on curcumin consumption with chemotherapy drugs, highlighting that curcumin increases the effectiveness of chemotherapy and radiotherapy which results in improving patient's survival time, and increasing the expression of anti-metastatic proteins along with reducing their side effects.. The comprehensive systematic review presented in this paper confirms that curcumin reduces the side effects of chemotherapy or radiotherapy, resulting in improving patients' quality of life. A number of studies reported that, curcumin has increased patient survival time and decreased tumor markers' level.

Topics: Antineoplastic Combined Chemotherapy Protocols; Cell Survival; Chemoradiotherapy; Curcumin; Drug-Related Side Effects and Adverse Reactions; Humans; Inflammation; Neoplasms; Neovascularization, Pathologic; Oxidative Stress; Quality of Life; Radiation Injuries

Curcumin is a plant-derived polyphenol extracted from the rhizome of turmeric. As curcumin has such favorable properties as anti-inflammation, anti-oxidation, anti-angiogenesis, immune regulation, anti-bacterial and pro-apoptosis and showed few side effects, the application of curcumin in prevention and treatment of periodontal diseases is promising. This article reviewed the research progress of curcumin in the prevention and treatment of periodontitis.. 姜黄素是一种从姜黄根茎中提取的天然植物类多酚。由于姜黄素具有抗炎、抗氧化、抗血管生成、免疫调节、抑菌和促进细胞凋亡等多种生物学作用，且安全无毒，不良反应小，使其在牙周病预防和治疗中具有潜在的应用前景。本文就近年来姜黄素在牙周炎防治方面的相关研究进展做一综述。.

Topics: Anti-Inflammatory Agents; Curcumin; Humans; Inflammation; Periodontitis

Traumatic Brain Injury (TBI) is one of the main causes of mortality and morbidity worldwide with no suitable treatment. The present study was designed to review the present literature about the protective effects of curcumin and the underlying mechanism against TBI. All published English language papers from beginning to 2019 were selected in this study. The findings indicate that curcumin may be effective against TBI outcomes by modulating the molecular signaling pathways involved in oxidative stress, inflammation, apoptosis, and autophagy. However, more experimental studies should be done to identify all mechanisms involved in the pathogenesis of TBI. Patents for Curcumin and chronic inflammation and traumatic brain injury management (WO2017097805A1 and US9101580B2) were published. In conclusion, the present study confirmed the potential therapeutic impact of curcumin for treating TBI.

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Apoptosis; Brain; Brain Injuries, Traumatic; Curcuma; Curcumin; Humans; Inflammation; Oxidative Stress; Patents as Topic; Phytotherapy; Plant Extracts

Inflammation is a biological function which triggered after the mechanical tissue disruption or from the responses by the incidence of physical, chemical or biological negotiator in body. These responses are essential act provided by the immune system during infection and tissue injury to maintain normal tissue homeostasis. Inflammation is a quite complicated process at molecular level with the involvement of several proinflammatory expressions. Several health problems are associated with prolonged inflammation, which effects nearly all major to minor diseases. The molecular and epidemiological studies jagged that the inflammation is closely associated with several disorders with their specific targets. It would be great achievement for human health around the world to overcome on inflammation. Mostly used anti-inflammatory drugs are at high risk of side effects and also expensive. Hence, the plant-based formulations gained a wide acceptance by the public and medical experts to treat it. Due to extensive dispersal, chemical diversity and systematically established biological potentials of natural products have induced renewed awareness as a gifted source for medications. However, today's urgent need to search for cheaper, more potent and safe anti-inflammatory medications to overcome on current situation. The goal of this review to compile an update on inflammation, associated diseases, molecular targets, inflammatory mediators and role of natural products. The entire text concise the involvement of various cytokines in pathogenesis of various human disorders. This assignment discussed about 321 natural products with their promising anti-inflammatory potential discovered during January 2009 to December 2018 with 262 citations.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Biological Products; Cardiovascular Diseases; Humans; Inflammation; Neoplasms; Skin Diseases

The most common inflammatory disease of the airways is asthma among children affecting around 235 million people worldwide. 5-Lipoxygenase (5-LOX) is a crucial enzyme which helps in the conversion of arachidonic acid (AA) to leukotrienes (LTs), the lipid mediators. It is associated with several inflammation related disorders such as asthma, allergy, and atherosclerosis. Therefore, it is considered as a promising target against inflammation and asthma. Currently, the only drug against 5-LOX which is available is Zileuton, while a few inhibitors are in clinical trial stages such as Atreleuton and Setileuton. So, there is a dire requirement in the area of progress of novel 5-LOX inhibitors which necessitates an understanding of their structure activity relationship and mode of action. In this review, novel 5-LOX inhibitors reported so far, their structural design, SAR and developmental strategies along with clinical updates are discussed over the last two decades.

Topics: Animals; Arachidonate 5-Lipoxygenase; Dose-Response Relationship, Drug; Drug Design; Humans; Inflammation; Leukotrienes; Lipoxygenase Inhibitors; Molecular Structure; Structure-Activity Relationship

Cardiovascular disorders are known as one of the main health problems which are associated with mortality worldwide. Myocardial ischemia (MI) is improper blood supply to myocardium which leads from serious complications to life-threatening problems like AMI, atherosclerosis, hypertension, cardiac-hypertrophy as well as diabetic associated complications as diabetic atherosclerosis/cardiomyopathy/hypertension. Despite several efforts, the current therapeutic platforms are not related with significant results. Hence, it seems, developing novel therapies are required. In this regard, increasing evidences indicated, curcumin (CRC) acts as cardioprotective agent. Given that CRC and its analogs exert their cardioprotective effects via affecting on a variety of cardiovascular diseases-related mechanisms (i.e., Inflammation, and oxidative stress). Herein, for first time, we have highlighted the protective impacts of CRC against MI. This review might be a steppingstone for further investigation into the clinical implications of the CRC against MI. Furthermore, it pulls in light of a legitimate concern for scientific community, seeking novel techniques and characteristic dynamic biopharmaceuticals for use against myocardial ischemia.

Topics: Animals; Cardiotonic Agents; Curcumin; Humans; Inflammation; Myocardial Ischemia; Oxidative Stress

The purpose of this review is to provide a concise overview of the polyphenol curcumin for improving arterial health, specifically endothelial function and arterial stiffness, to reduce cardiovascular disease (CVD) risk and to highlight potential mechanisms of action by which curcumin may improve artery function.. The primary findings of this review support the notion for curcumin to improve arterial health both with aging and obesity. There are few clinical trials on curcumin, and those that currently exist are small in scale but provide evidence for curcumin to improve endothelial function in older adults and reduce arterial stiffness in young, obese men. The antioxidant and anti-inflammatory properties of curcumin appear to be important targets of curcumin that are related to improved arterial health. Mechanistic studies have revealed superoxide dismutase, heme oxygenase-1 and nuclear factor erythroid 2-related factor 2 as emerging targets for the beneficial effects of curcumin on the vasculature.. In summary, the efficacy of curcumin for improving arterial function is promising in the limited number of clinical studies performed to date. Still, much investigation is needed to elucidate the effectiveness of curcumin for improving arterial health to lower CVD risk.

Topics: Anti-Inflammatory Agents; Antioxidants; Arteries; Curcumin; Humans; Inflammation; Oxidative Stress; Vascular Diseases; Vascular Stiffness

Curcumin (diferuloylmethane), a yellowish agent extracted from turmeric, is a bioactive compound known for its anti-inflammatory, antiproliferative, antidiabetic, and anticancer activities. Multiple lines of evidence have indicated that curcumin regulates several regulatory proteins in the cellular signal transduction pathway. AMP-activated protein kinase (AMPK) is one of the central regulators of cellular metabolism and energy homeostasis, which is activated in response to increasing cellular adenosine monophosphate/adenosine triphosphate ratio. AMPK plays a critical role in regulating growth and reprogramming metabolism and is linked to several cellular processes including apoptosis and inflammation. Recently, it has been demonstrated that AMPK is a new molecular target affected by curcumin and its derivatives. In this review, we discuss recent findings on the targeting of AMPK signaling by curcumin and the resulting impact on the pathogenesis of proinflammatory diseases. We also highlight the therapeutic value of targeting AMPK by curcumin in the prevention and treatment of proinflammatory diseases, including cancers, atherosclerosis, and diabetes.

Topics: AMP-Activated Protein Kinases; Apoptosis; Curcumin; Diabetes Mellitus; Energy Metabolism; Humans; Inflammation; Neoplasms

Besides other benefits, curcumin is getting more recognized for its antioxidant and anti-inflammatory properties, highlighting the importance of curcumin application for chronic disease prevention. This systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted to assess the influence of curcumin-containing supplements on biomarkers of inflammation and oxidative stress. MEDLINE, EMBASE, Web of Science, and Cochrane Central Register of Controlled Trials were searched till January 2018 for eligible studies. The selected studies were evaluated for their quality using the Cochrane risk of bias tool and relevant data were extracted from included studies. Data were pooled using the inverse variance method and expressed as standardized mean difference (SMD) with 95% confidence intervals (95% CI). Fifteen RCTs were included in the final analysis. The meta-analysis indicated that curcumin supplementation significantly decreased interleukin 6 (IL-6) (SMD -2.08; 95% CI [-3.90, -0.25]; p = 0.02), high-sensitivity C-reactive protein (hs-CRP) (SMD -0.65; 95% CI [-1.20, -0.10], p = 0.02), and malondialdehyde (MDA) concentrations (SMD -3.14; 95% CI [-4.76, -1.53], p < 0.001). Though, curcumin supplementation had no significant effect on tumor necrosis factor-alpha (SMD -1.62; 95% CI [-3.60, 0.36]; p = 0.10) and superoxide dismutase levels (SMD 0.34; 95% CI [-1.06, 1.74], p = 0.63). Overall, this meta-analysis suggests that taking curcumin-containing supplements may exert anti-inflammatory and antioxidant properties through a significant reduction in IL-6, hs-CRP, and MDA levels.

Topics: Antioxidants; Biomarkers; C-Reactive Protein; Curcumin; Dietary Supplements; Humans; Inflammation; Interleukin-6; Malondialdehyde; Oxidative Stress; Randomized Controlled Trials as Topic; Superoxide Dismutase

Neuroinflammatory disease is a general term used to denote the progressive loss of neuronal function or structure. Many neuroinflammatory diseases, including Alzheimer's, Parkinson's, and multiple sclerosis (MS), occur due to neuroinflammation. Neuroinflammation increases nuclear factor-κB (NF-κB) levels, cyclooxygenase-2 enzymes and inducible nitric oxide synthase, resulting in the release of inflammatory cytokines, such as interleukin-6 (IL-6), interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α). It could also lead to cellular deterioration and symptoms of neuroinflammatory diseases. Recent studies have suggested that curcumin (the active ingredient in turmeric) could alleviate the process of neuroinflammatory disease. Thus, the present mini-review was conducted to summarize studies regarding cellular and molecular targets of curcumin relevant to neuroinflammatory disorders.. A literature search strategy was conducted for all English-language literature. Studies that assessed the various properties of curcuminoids in respect of neuroinflammatory disorders were included in this review.. The studies have suggested that curcuminoids have significant anti- neuroinflammatory, antioxidant and neuroprotective properties that could attenuate the development and symptom of neuroinflammatory disorders. Curcumin can alleviate neurodegeneration and neuroinflammation through multiple mechanisms, by reducing inflammatory mediators (such as TNF-α, IL-1β, nitric oxide and NF-κB gene expression), and affect mitochondrial dynamics and even epigenetic changes.. It is a promising subject of study in the prevention and management of the neuroinflammatory disease. However, controlled, randomized clinical trials are needed to fully evaluate its clinical potential.

Topics: Animals; Curcumin; Humans; Inflammation; Inflammation Mediators; Nervous System Diseases

Multiple sclerosis (MS) is a disease that has shown a considerable increase in prevalence in recent centuries. Current knowledge about its etiology is incomplete, and therefore it cannot be managed optimally utilizing targeted therapeutic regimens at each stage of the disease. MS progresses in different stages, beginning with a cascade of inflammation. The pivotal spark to initiate this cascade seems to be the migration of Th17 into the central nervous system across the blood-brain barrier (BBB) through the disrupted tight junctions. Coupling of interleukin (IL)-17 and IL-22 to their receptors in the BBB layer facilitates this migration. Subsequently, axon degeneration and the various manifestations of nerve-muscle disorders appear. Curcumin, a major component of turmeric, is derived from Curcuma longa, which belongs to the Zingiberaceae family. Numerous properties of curcumin have been identified recently, some of which can be effective in the treatment of MS, particularly the anti-inflammatory properties via inhibition of secretion of proinflammatory cytokines. In this paper, we will review the various properties and key effects of curcumin for the treatment of MS.

Topics: Animals; Anti-Inflammatory Agents; Curcuma; Curcumin; Cytokines; Humans; Inflammation; Multiple Sclerosis; Plant Extracts

Curcuma longa L., its derived extracts and even its major compound curcumin has a long history of use and doubtless effectiveness, reported through increasingly detailed in vitro, ex vivo, in vivo and even clinical trials. Regarding its biological effects, multiple health-promoting, disease-preventing and even treatment attributes has been remarkably highlighted. Clinical trials, although have increased in a progressive manner, significant disproportionalities have been stated in terms of biological effects assessment. In this sense, the present report aims to provide an extensive overview to curcumin therapeutic effects in human subjects. For that, clinical trials assessing the curcumin effect on inflammation, skin, eye, central nervous system, respiratory, cardiovascular, gastrointestinal, urogenital and metabolic disorders are here presented and discussed. A special emphasis was also given to curcumin activity on intoxications and multiple malignant diseases.

Topics: Clinical Trials as Topic; Curcuma; Curcumin; Humans; Inflammation; Metabolic Diseases

Substantial human and preclinical studies have shown that curcumin, a dietary compound from turmeric, has a variety of health-promoting effects including but not limited to antioxidant, antimicrobial, anti-inflammatory, and anticancer actions. However, curcumin has poor bioavailability, and high doses of curcumin are usually needed to exert its health-promoting effects in vivo, limiting its applications for disease prevention. Here, we discuss the health-promoting effects of curcumin, factors limiting its bioavailability, and strategies to improve its oral bioavailability.

Topics: Administration, Oral; Biological Availability; Curcumin; Humans; Inflammation

As a natural extract from turmeric, curcumin has extensive pharmacological effects, such as anti-tumor, anti-inflammation, anti-oxidative stress, anti-microbial, immunoregulation and so on. In recent years, an increasing number of basic and clinical researches have shown that curcumin takes therapeutic effects on various diseases, such as gastrointestinal diseases, cardiovascular diseases, autoimmune diseases, neuropsychiatric diseases and so on. Many of the pharmacological effects and mechanisms of curcumin are associated with protective effects of intestinal mucosal barrier. It can protect intestinal mucosal barrier through mutiple pathways, including anti-inflammation, anti-oxidative stress, anti-bacterial, anti-apoptosis, regulating intestinal microecology and intestinal immune response and so on. This paper summarizes the protective effects of curcumin on intestinal barrier function and the mechanism, in order to provide new ideas for diagnosis and treatment of intestinal dysfunction.. 姜黄素作为一种源于姜黄的天然提取物质，具有抗肿瘤、抗炎、抗氧化应激、抗微生物、调节免疫等多方面药理作用。近年来越来越多的基础及临床研究证明姜黄素对多种疾病具有治疗作用，如胃肠道疾病、心血管疾病、自身免疫性疾病、神经精神性疾病等。姜黄素的诸多药理作用及机制均与肠黏膜屏障功能保护相关，它可通过抗炎、抗氧化应激、抗菌、调节肠道微生态和肠道免疫反应、抗凋亡等多种途径保护肠黏膜屏障。本文综述姜黄素对肠黏膜屏障功能的保护作用及其机制，为肠功能障碍的诊治提供新思路。.

Topics: Anti-Inflammatory Agents; Curcumin; Humans; Inflammation; Intestinal Mucosa; Intestines; Oxidative Stress

Pleiotropic effects of curcumin have been the subject of intensive research. The interest in this molecule for preventive medicine may further increase because of its potential to modulate inflamm-aging. Although direct data related to its effect on inflamm-aging does not exist, there is a strong possibility that its well-known anti-inflammatory properties may be relevant to this phenomenon. Curcumin's binding to various proteins, which was shown to be dependent on cellular oxidative status, is yet another feature for exploration in depth. Finally, the binding of curcumin to various metabolic enzymes is crucial to curcumin's interference with powerful metabolic machinery, and can also be crucial for metabolic reprogramming of cancer cells. This review offers a synthesis and functional links that may better explain older data, some observational, in light of the most recent findings on curcumin. Our focus is on its modes of action that have the potential to alleviate specific morbidities of the 21st century.

Topics: Aging; Animals; Anti-Inflammatory Agents, Non-Steroidal; Antineoplastic Agents; Curcuma; Curcumin; Humans; Inflammation; Neoplasms; Oxidative Stress

Intestinal inflammatory diseases, such as Crohn's disease, ulcerative colitis, and necrotizing enterocolitis, are becoming increasingly prevalent. While knowledge of the pathogenesis of these related diseases is currently incomplete, each of these conditions is thought to involve a dysfunctional, or overstated, host immunological response to both bacteria and dietary antigens, resulting in unchecked intestinal inflammation and, often, alterations in the intestinal microbiome. This inflammation can result in an impaired intestinal barrier allowing for bacterial translocation, potentially resulting in systemic inflammation and, in severe cases, sepsis. Chronic inflammation of this nature, in the case of inflammatory bowel disease, can even spur cancer growth in the longer-term. Recent research has indicated certain natural products with anti-inflammatory properties, such as curcumin, can help tame the inflammation involved in intestinal inflammatory diseases, thus improving intestinal barrier function, and potentially, clinical outcomes. In this review, we explore the potential therapeutic properties of curcumin on intestinal inflammatory diseases, including its antimicrobial and immunomodulatory properties, as well as its potential to alter the intestinal microbiome. Curcumin may play a significant role in intestinal inflammatory disease treatment in the future, particularly as an adjuvant therapy.

Topics: Biological Products; Colitis, Ulcerative; Crohn Disease; Curcumin; Gastrointestinal Microbiome; Humans; Inflammation; Intestinal Mucosa; Intestines

Acute lung injury (ALI) is characterized by acute inflammation and tissue injury results in dysfunction of the alveolar epithelial membrane. If the epithelial injury is severe, a fibroproliferative phase of ALI can develop. During this phase, the activated fibroblast and myofibroblasts synthesize excessive collagenous extracellular matrix that leads to a condition called pulmonary fibrosis. Lung injury can be caused by several ways; however, the present review focus on bleomycin (BLM)-mediated changes in the pathology of lungs. BLM is a chemotherapeutic agent and has toxic effects on lungs, which leads to oxidative damage and elaboration of inflammatory cytokines. In response to the injury, the inflammatory cytokines will be activated to defend the system from injury. These cytokines along with growth factors stimulate the proliferation of myofibroblasts and secretion of pathologic extracellular matrix. During BLM injury, the pro-inflammatory cytokine such as IL-17A will be up-regulated and mediates the inflammation in the alveolar epithelial cell and also brings about recruitment of certain inflammatory cells in the alveolar surface. These cytokines probably help in up-regulating the expression of p53 and fibrinolytic system molecules during the alveolar epithelial cells apoptosis. Here, our key concern is to provide the adequate knowledge about IL-17A-mediated p53 fibrinolytic system and their pathogenic progression to pulmonary fibrosis. The present review focuses mainly on IL-17A-mediated p53-fibrinolytic aspects and how curcumin is involved in the regulation of pathogenic progression of ALI and pulmonary fibrosis.

Topics: Acute Lung Injury; Alveolar Epithelial Cells; Animals; Bleomycin; Curcumin; Humans; Inflammation; Interleukin-17; Pulmonary Fibrosis; Tumor Suppressor Protein p53

Turmeric extract or active component curcumin may have anti-inflammatory effects in people with chronic inflammatory diseases. The effect of turmeric or curcumin on a wide range of inflammatory markers has not been evaluated in a systematic review. We performed a systematic review of randomized controlled trials (RCTs) evaluating the effects of oral turmeric or curcumin on inflammatory markers (CRP, hsCRP, IL-1, IL-6, TNF) in patients with a wide range of chronic inflammatory diseases. Pubmed, EMBASE, Scopus, the Web of Science, and the Cochrane library were evaluated until June 2018. Random effects meta-analyses with inverse variance methods and stratified by turmeric or curcumin were performed. Effects were expressed as mean differences (MD) and their 95% confidence intervals (CI). Risk of bias of RCTs was evaluated with the Cochrane tool. Nineteen RCTs were identified; included patients had rheumatic diseases, advanced chronic kidney disease with hemodialysis, metabolic syndrome, and cardiovascular diseases. Turmeric was the intervention in 5 RCTs (n = 356) and curcumin/curcuminoids in 14 RCTs (n = 988). Follow up times ranged between 4 and 16 weeks. One RCT had high risk of bias. In comparison to controls, turmeric or curcumin did not significantly decrease levels of CRP (MD -2.71 mg/L, 95%CI -5.73 to 0.31, p = 0.08, 5 studies), hsCRP (MD -1.44 mg/L, 95%CI -2.94 to 0.06, p = 0.06, 6 studies), IL-1 beta (MD -4.25 pg/mL, 95%CI -13.32 to 4.82, p = 0.36, 2 studies), IL-6 (MD -0.71 pg/mL, 95%CI -1.68 to 0.25, p = 0.15), and TNF alpha (MD -1.23 pg/mL, 95%CI -3.01 to 0.55, p = 0.18, 7 studies). There were no differences between turmeric and curcumin interventions. High heterogeneity of effects was observed for all markers across studies, except hsCRP. Other inflammatory markers such as IL-1 alpha, TNF beta, IL-17, and IL-22 had scarce data. Turmeric or curcumin did not decrease several inflammatory markers in patients with chronic inflammatory diseases.

Topics: Administration, Oral; Anti-Inflammatory Agents; Biomarkers; Chronic Disease; Curcuma; Curcumin; Humans; Inflammation; Plant Extracts; Randomized Controlled Trials as Topic

Curcumin is a natural compound derived from the spice, turmeric, that has been extensively reported for its efficacy in controlling or treatment of several inflammatory diseases. There is a growing body of literature that recognizes the anti-inflammatory effects of curcumin in the immune system. On the other hand, the role of inflammatory signaling pathways has been highlighted in the pathogenesis of several inflammatory diseases, and signaling molecules involved in these pathways are considered as valuable targets for new treatment approaches. We aimed to provide a comprehensive overview of the modulatory effects of curcumin on inflammatory signaling pathways which leads to inhibition of inflammation in different types of immune cells and animal models. In this comprehensive review, we elaborate on how curcumin can effectively inhibit multiple signaling molecules involved in inflammation including NF-κB, JAKs/STATs, MAPKs, β-catenin, and Notch-1.

Topics: Animals; Curcumin; Humans; Immune System; Inflammation; Signal Transduction

Numerous studies have presented that curcumin could have a positive effect in the prevention of cancer and then in tumor therapy. Several hypotheses have highlighted that curcumin could decreases tumor growth and invasion by acting on both chronic inflammation and oxidative stress. This review focuses on the interest of use curcumin in cancer therapy by acting on the WNT/β-catenin pathway to repress chronic inflammation and oxidative stress. In the cancer process, one of the major signaling pathways involved is the WNT/β-catenin pathway, which appears to be upregulated. Curcumin administration participates to the downregulation of the WNT/β-catenin pathway and thus, through this action, in tumor growth control. Curcumin act as PPARγ agonists. The WNT/β-catenin pathway and PPARγ act in an opposed manner. Chronic inflammation, oxidative stress and circadian clock disruption are common and co-substantial pathological processes accompanying and promoting cancers. Circadian clock disruption related to the upregulation of the WNT/β-catenin pathway is involved in cancers. By stimulating PPARγ expression, curcumin can control circadian clocks through the regulation of many key circadian genes. The administration of curcumin in cancer treatment would thus appear to be an interesting therapeutic strategy, which acts through their role in regulating WNT/β-catenin pathway and PPARγ activity levels.

Topics: Cell Proliferation; Circadian Clocks; Curcumin; Gene Expression Regulation, Neoplastic; Humans; Inflammation; Neoplasm Invasiveness; Neoplasms; Oxidative Stress; PPAR gamma; Wnt Signaling Pathway

It has been extensively verified that inflammation and oxidative stress play important roles in the pathogenesis of cardiovascular diseases (CVDs). Curcuminoids, from the plant Curcuma longa, have three major active ingredients, which include curcumin (curcumin I), demethoxycurcumin, and bisdemethoxycurcumin. Curcuminoids have been used in traditional medicine for CVDs' management and other comorbidities for centuries. Numerous studies had delineated their anti-inflammatory, antioxidative, and other medicinally relevant properties. Animal experiments and clinical trials have also demonstrated that turmeric and curcuminoids can effectively reduce atherosclerosis, cardiac hypertrophy, hypertension, ischemia/reperfusion injury, and diabetic cardiovascular complications. In this review, we introduce and summarize curcuminoids' molecular and biological significance, while focusing on their mechanistic anti-inflammatory/antioxidative involvements in CVDs and preventive effects against CVDs, and, finally, discuss relevant clinical applications.

Topics: Animals; Cardiovascular Diseases; Curcuma; Humans; Inflammation; Oxidative Stress; Plant Extracts

Inflammation comprises the reaction of the body to injury, in which a series of changes of the terminal vascular bed, blood, and connective tissue tends to eliminate the injurious agent and to repair the damaged tissue. It is a complex process, which involves the release of diverse regulatory mediators. The current anti-inflammatory agents are challenged by multiple side effects and thus, new effective therapies are highly needed. The aim of this review is to summarize the described microsomal prostaglandin E synthase-1 (mPGES-1) inhibitors or transcriptional suppressors from medicinal plants, which could be an ideal approach in the management of inflammatory disorders, but need further clinical trials in order to be ultimately validated.

Topics: Animals; Anti-Inflammatory Agents; Biological Products; Drug Discovery; Enzyme Inhibitors; Humans; Inflammation; Plants, Medicinal; Prostaglandin-E Synthases

Ligustrazine is a main active fraction of the traditional medicine known as Ligusticum chuanxiong hort, which has been used as clinical medication for cerebral thrombosis, coronary heart disease and stenocardia recently. The rapid metabolism and short half-life of ligustrazine seriously limits its application in clinical practice. Therefore, derivatives of ligustrazine are designed and synthesized in our and other labs, including piperazine, cinnamic acid, styrene, acylguanidine, amides, curcumin and triterpenes derivatives of ligustrazine. Most of these compounds present better pharmacodynamics activities and more favorable pharmacokinetic properties compared to the parent compound. Besides, some new biological activities of these compounds are discovered. Hence, this review continues the previous review of our group as well as aims to highlight recent prominent advances in this field in the past ten years.

Topics: Animals; Anti-Bacterial Agents; Anti-Inflammatory Agents, Non-Steroidal; Antineoplastic Agents; Bacteria; Cardiovascular Diseases; Humans; Inflammation; Molecular Structure; Neoplasms; Neuroprotective Agents; Pyrazines

Curcumin, from the spice turmeric, exhibits anti-inflammatory, antioxidant, anticancer, antiviral, and neurotrophic activity and therefore holds promise as a therapeutic agent to prevent and treat several disorders. However, a major barrier to curcumin's clinical efficacy is its poor bioavailability. Efforts have therefore been dedicated to developing curcumin formulations with greater bioavailability and systemic tissue distribution. However, it is proposed in this review that curcumin's potential as a therapeutic agent may not solely rely on its bioavailability, but rather its medicinal benefits may also arise from its positive influence on gastrointestinal health and function. In this review, in vitro, animal, and human studies investigating the effects of curcumin on intestinal microbiota, intestinal permeability, gut inflammation and oxidative stress, anaphylactic response, and bacterial, parasitic, and fungal infections are summarized. It is argued that positive changes in these areas can have wide-ranging influences on both intestinal and extraintestinal diseases, and therefore presents as a possible mechanism behind curcumin's therapeutic efficacy.

Topics: Animals; Anti-Inflammatory Agents; Biological Availability; Curcumin; Gastrointestinal Microbiome; Gastrointestinal Tract; Health Promotion; Health Status; Humans; Infections; Inflammation; Intestinal Mucosa; Intestines; Oxidative Stress; Permeability

Curcumin, a low molecular weight, lipophilic, major yellow natural polyphenolic, and the most well-known plant-derived compound, is extracted from the rhizomes of the turmeric (

Topics: Aging; Arthritis, Rheumatoid; Atherosclerosis; Cardiovascular Diseases; Clinical Trials as Topic; Curcumin; Diabetes Mellitus; Humans; Inflammation; Molecular Structure; Neoplasms; Neurodegenerative Diseases; Osteoporosis

The rate of cognitive decline in the elderly is highly variable. One potential factor contributing to accelerated cognitive decline is chronic systemic inflammation, because it has been linked to cognitive impairment and increased dementia risk. Certain lifestyle factors, such as excess body weight and sedentary behavior, can exacerbate a proinflammatory state in older adults, resulting in chronic low-grade inflammation. Supplementing the diet with curcumin, an anti-inflammatory polyphenolic compound from the curry spice turmeric, is a potential approach to prevent accelerated cognitive decline by counteracting chronic inflammatory processes. Although the anti-inflammatory effects of curcumin are well established, the potential cognitive benefits of curcumin were discovered more recently. Several animal and epidemiologic studies on the effect of curcumin supplementation on cognition showed promising results; however, randomized controlled trials in humans are limited. In this review, we identified 5 randomized controlled trials, of which only 2 observed a beneficial effect of curcumin supplementation on cognition by improving working memory. By critically examining the methodologies of those studies, we identified some limitations, one of which is that none of the studies explored the possibility that anti-inflammatory mechanisms were mediating cognitive benefits (i.e., no study tested participants with low-grade inflammation or measured inflammatory biomarkers). Other factors influencing the likelihood of conclusive outcomes include choice of study population (cognitively unimpaired compared with impaired), study duration, curcumin dose and its bioavailability, and neurocognitive test battery. On the basis of these findings, we offer recommendations for future studies to examine the potential cognitive benefits of curcumin in humans, which include evaluating its effects on cerebral endothelial vasodilator function and boosting its cognitive effects by combining it with long-chain omega-3 (n-3) fatty acids.

Topics: Animals; Anti-Inflammatory Agents; Cognition; Cognitive Dysfunction; Curcuma; Curcumin; Dementia; Dietary Supplements; Fatty Acids, Omega-3; Female; Humans; Inflammation; Male; Memory; Phytotherapy; Polyphenols

Processes such as aberrant redox signaling and chronic low-grade systemic inflammation have been reported to modulate age-associated pathologies such as cognitive impairment. Curcumin, the primary therapeutic component of the Indian spice, Turmeric (Curcuma longa), has long been known for its strong anti-inflammatory and antioxidant activity attributable to its unique molecular structure. Recently, an interest in this polyphenol as a cognitive therapeutic for the elderly has emerged. The purpose of this paper is to critically review preclinical and clinical studies that have evaluated the efficacy of curcumin in ameliorating and preventing age-associated cognitive decline and address the translational progress of preclinical to clinical efficacy. PubMed, semantic scholar, and Google scholar searches were used for preclinical studies; and clinicaltrials.gov , the Australian and New Zealand clinical trials registry, and PubMed search were used to select relevant completed clinical studies. Results from preclinical studies consistently demonstrate curcumin and its analogues to be efficacious for various aspects of cognitive impairment and processes that contribute to age-associated cognitive impairment. Results of published clinical studies, while mixed, continue to show promise for curcumin's use as a therapeutic for cognitive decline but overall remain inconclusive at this time. Both in vitro and in vivo studies have found that curcumin can significantly decrease oxidative stress, systemic inflammation, and obstruct pathways that activate transcription factors that augment these processes. Future clinical studies would benefit from including evaluation of peripheral and cerebrospinal fluid biomarkers of dementia and behavioral markers of cognitive decline, as well as targeting the appropriate population.

Topics: Aged; Aged, 80 and over; Aging; Animals; Animals, Genetically Modified; Australia; Cognitive Dysfunction; Cohort Studies; Curcumin; Female; Humans; Inflammation; Male; Middle Aged; Models, Animal; Narration; New Zealand; Oxidative Stress; Treatment Outcome

Curcumin quite possibly represents one of the most diverse therapeutic agents yet isolated from natural sources. Therapeutic benefits of this extraordinary natural compound have been demonstrated during treatment of a variety of diseases, including cancer, inflammatory processes, immunological disorders, Diabetes, and oxidative stress often associated with hyperlipidemia. Due to its unique molecular chemical structure and functional groups, curcumin may bind with and subsequently either inhibit or activate a variety of endogenous biomolecules, including enzymes, receptors, signaling molecules, metals, transcription factors, and even certain proteins located in cell membranes. In fact, curcumin exerts pharmacologically useful effects through non-covalent interactions with biomolecules. With so many varied biological targets, curcumin (a polyphenol) elicits numerous pleiotropic effects, which is therapeutically advantageous owing to the fact that many pathological disease states involve more than one signaling pathway, receptor, protein/enzyme, or gene. In this paper, we will discuss the underlying mechanisms responsible for the chemical interaction of curcumin with selected classes of biomolecules, rather than attempt to provide an exhaustive list of each and every biomolecule with which curcumin may chemically interact.

Topics: Animals; Curcumin; Humans; Hyperlipidemias; Immune System Diseases; Inflammation; Molecular Structure; Neoplasms; Oxidative Stress

Immune dysfunction is caused by various factors, including changes in relevant immune regulators and environmental stress. Immune system imbalance leads to a variety of diseases in humans. Nutrition may play an essential role in immunity by interfering with proinflammatory cytokine synthesis, immune cell regulation, and gene expression. Polyphenols, one of many categories of natural substances, exhibit a range of biological activities. Polyphenols promote immunity to foreign pathogens via various pathways. Different immune cells express multiple types of polyphenol receptors that recognise and allow cellular uptake of polyphenols, which subsequently activate signalling pathways to initiate immune responses. Furthermore, the polyphenols curcumin and epigallocatechin gallate can induce epigenetic changes in cells. In summary, polyphenols can be used to regulate intestinal mucosal immune responses, allergic diseases, and antitumour immunity.

Topics: Animals; Catechin; Curcumin; Epigenesis, Genetic; Humans; Hypersensitivity; Immunity; Immunomodulation; Inflammation; Neoplasms; Nutritional Physiological Phenomena; Oxidative Stress; Polyphenols; Signal Transduction

Atherosclerosis (AS), a chronic arterial disease, is one of the major causes of morbidity and mortality worldwide. Several treatment modalities have been demonstrated to be effective in treating AS; however, the mortality rate due to AS remains high. Sonodynamic therapy (SDT) is a promising new treatment using low-intensity ultrasound in combination with sonosensitizers. Although SDT was developed from photodynamic therapy (PDT), it has a stronger tissue-penetrating capability and exhibits a more focused effect on the target lesional site requiring treatment. Furthermore, SDT has been demonstrated to suppress the formation of atheromatous plaques, and it can increase plaque stability both in vitro and in vivo. In this article, we critically summarize the recent literature on SDT, focusing on its possible mechanism of action as well as the existing and newly discovered sonosensitizers and chemotherapeutic agents for the treatment of AS.

Topics: Animals; Anthracenes; Antineoplastic Agents; Apoptosis; Atherosclerosis; Berberine; Cell Death; Chalcone; Curcumin; Emodin; Humans; Inflammation; Macrophages; Matrix Metalloproteinases; Mice; Neoplasms; Perylene; Photochemotherapy; Plaque, Atherosclerotic; Quinones; Reactive Oxygen Species; THP-1 Cells; Ultrasonic Therapy

Cognitive impairment results from a complex interplay of many factors. The most important independent predictor of cognitive decline is age but other contributing factors include demographic, genetic, socio-economic, and environmental parameters, including nutrition. The number of persons with cognitive decline and dementia will increase in the next decades in parallel with aging of the world population. Effective pharmaceutical treatments for age-related cognitive decline are lacking, emphasizing the importance of prevention strategies. There is extensive evidence supporting a relationship between diet and cognitive functions. Thus, nutritional approaches to prevent or slow cognitive decline could have a remarkable public health impact. Several dietary components and supplements have been examined in relation to their association with the development of cognitive decline. A number of studies have examined the role of dietary patterns on late-life cognition, with accumulating evidence that combinations of foods and nutrients may act synergistically to provide stronger benefit than those conferred by individual dietary components. Higher adherence to the Mediterranean dietary pattern has been associated with decreased cognitive decline and incident AD. Another dietary pattern with neuroprotective actions is the Dietary Approach to Stop Hypertension (DASH). The combination of these two dietary patterns has been associated with slower rates of cognitive decline and significant reduction in incident AD. This review evaluates the evidence for the effects of some dietary components, supplements, and dietary patterns as neuroprotective, with potential to delay cognitive decline and the onset of dementia.

Topics: Antioxidants; Autophagy; Caffeine; Catechin; Central Nervous System Stimulants; Chocolate; Cognitive Dysfunction; Curcumin; Dementia; Diet; Fatty Acids, Omega-3; Garlic; Ginkgo biloba; Healthy Aging; Humans; Inflammation; Magnesium; Oxidative Stress; Phytoestrogens; Phytotherapy; Resveratrol; Tea; Vitamins

Obesity in the 21st century society became an important health problem, alarming both the scientists and medicine doctors around the world. That is why, the search for new drug candidates capable to reduce the body weight is of high concern.. This contribution tends to collect current findings on the biochemistry of obesity and on the application of plants and in particular turmeric tuber - a commonly used spice - as an anti-obesity agent.. Following an introduction on the biochemical characteristics of obesity, the description of Curcuma secondary metabolites, their pharmacological applications and a study on the plants' regulatory properties in obesity was summarized. Particular attention was paid to curcumin - the major metabolite present in the extracts of Curcuma spp., which is known to exhibit a variety of pharmacological actions. Also, the characteristics of some semisynthetic analogues of this ferulic acid derivative, characterized by a higher polarity and better bioavailability will be discussed.. Numerous scientific papers treat on the influence of turmeric on weight loss. Additionally, some of them describe its anti-inflammatory properties.. This important spice tends to fight the 21st century plague, which is an excessive weight gain, related to the development of metabolic syndrome, to the occurrence of cardiovascular problems and diabetes, and, in consequence, leading to a significant shortening of life span. As herein proven, the extracts of turmeric play an important role in the regulation of inflammatory reactions which are evoked in the overweight patients, helping them reduce the excess body weight.

Topics: Adipose Tissue; Animals; Anti-Inflammatory Agents; Anti-Obesity Agents; Antioxidants; Biological Availability; Biological Products; Curcuma; Curcumin; Humans; Inflammation; Obesity; Plant Extracts; Plant Tubers

Curcumin is a dietary polyphenol from turmeric with numerous pharmacological activities. Novel animal and human studies indicate that curcumin can affect different immune cells, such as various T lymphocyte subsets, macrophages, dendritic cells, B lymphocytes and natural killer cells, which results in decreasing severity of various diseases with immunological etiology. The present review provides a comprehensive overview of the effects of curcumin on different immune cells and immune system-related diseases.

Topics: Animals; Curcumin; Humans; Immune System Diseases; Immunologic Factors; Inflammation; Inflammation Mediators; Signal Transduction

Curcumin, extracted mainly from Curcuma longa rhizomes, has been reported to possess potent anti-inflammatory and anti-oxidant activities. Although safe at higher doses and exhibiting multiple biological activities, curcumin still has the problem of poor bioavailability which has been an attractive area of research over the last few years. A number of efforts have been made by modifying structural features of curcumin. This review highlights the structurally modified and more stable newly synthesized curcumin analogs that have been screened against antioxidant and anti-inflammatory activities. Also the structure-activity relationship to gain insight into future guidelines for scheming new compounds has been discussed, and further these analogs being more stable may serve as promising agents for use in different pathological conditions.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Antioxidants; Curcumin; Humans; Inflammation; Lipid Peroxidation; Molecular Structure; Structure-Activity Relationship

Natural products or nutraceuticals promote anti-aging, anti-cancer and other health-enhancing effects. A key target of the effects of natural products may be the regulation of the PI3K/PTEN/Akt/mTORC1/GSK-3 pathway. This review will focus on the effects of curcumin (CUR), berberine (BBR) and resveratrol (RES), on the PI3K/PTEN/Akt/mTORC1/GSK-3 pathway, with a special focus on GSK-3. These natural products may regulate the pathway by multiple mechanisms including: reactive oxygen species (ROS), cytokine receptors, mirco-RNAs (miRs) and many others. CUR is present the root of turmeric (Curcuma longa). CUR is used in the treatment of many disorders, especially in those involving inflammatory processes which may contribute to abnormal proliferation and promote cancer growth. BBR is also isolated from various plants (Berberis coptis and others) and is used in traditional medicine to treat multiple diseases/conditions including: diabetes, hyperlipidemia, cancer and bacterial infections. RES is present in red grapes, other fruits and berries such as blueberries and raspberries. RES may have some anti-diabetic and anti-cancer effects. Understanding the effects of these natural products on the PI3K/PTEN/Akt/mTORC1/GSK-3 pathway may enhance their usage as anti-proliferative agent which may be beneficial for many health problems.

Topics: Berberine; Cardiovascular Diseases; Curcumin; Gene Expression Regulation; Glycogen Synthase Kinase 3; Humans; Inflammation; Mechanistic Target of Rapamycin Complex 1; Neoplasms; Neurodegenerative Diseases; Osteoarthritis; Phosphatidylinositol 3-Kinases; Protective Agents; Proto-Oncogene Proteins c-akt; PTEN Phosphohydrolase; Resveratrol; Signal Transduction; Stilbenes

Oxidative damage and inflammation have been identified, through clinical and preclinical studies, as the main causes of nonhealing chronic wounds. Reduction of persistent chronic inflammation by application of antioxidant and anti-inflammatory agents such as curcumin has been well studied. However, low aqueous solubility, poor tissue absorption, rapid metabolism and short plasma half-life have made curcumin unsuitable for systemic administration for better wound healing. Recently, various topical formulations of curcumin such as films, fibers, emulsion, hydrogels and different nanoformulations have been developed for targeted delivery of curcumin at wounded sites. In this review, we summarize and discuss different topical formulations of curcumin with emphasis on their wound-healing properties in animal models.

Topics: Administration, Cutaneous; Animals; Chemistry, Pharmaceutical; Curcumin; Humans; Inflammation; Skin; Solubility; Wound Healing

Inflammation can promote the development of arthritis, obesity, cardiovascular, type II diabetes, pancreatitis, metabolic and neurodegenerative diseases, and certain types of cancer. Compounds isolated from plants have been practiced since ancient times for curing various ailments including inflammatory disorders and to support normal physiological functions. Curcumin (diferuloylmethane) is a yellow coloring agent, extracted from turmeric that has been used for the prevention and treatment of various inflammatory diseases. Numerous studies have shown that curcumin modulate multiple molecular targets and can be translated to the clinics for multiple therapeutic processes. There is compelling evidence that curcumin can block cell proliferation, invasion, and angiogenesis as well as reduced the prolonged survival of cancer cells. Curcumin mediates anti-inflammatory effect through downregulation of inflammatory cytokines, transcription factors, protein kinases, and enzymes that promote inflammation and development of chronic diseases. In addition, curcumin induces apoptosis through mitochondrial and receptor-mediated pathways by activating caspase cascades. Curcumin is a safe and nontoxic drug that has been reported to be well tolerated. Available clinical trials support the potential role of curcumin for treatment of various inflammatory disorders. However, curcumin's efficacy is hindered by poor absorption and low bioavailability, which limit its translation into clinics. This review outlines the potential pharmacological and clinical role of curcumin, which provide a gateway for the beneficial role of plant isolated compounds in treatment of various inflammatory diseases and cancer.

Topics: Animals; Curcuma; Curcumin; Diabetes Mellitus, Type 2; Humans; Inflammation; Neoplasms; Neurodegenerative Diseases; Obesity

Diabetes, especially type 2, has been rapidly increasing all over the world. Although many drugs have been developed and used to treat diabetes, side effects and long-term efficacy are of great challenge. Therefore, natural health product and dietary supplements have been of increasing interest alternatively. In this regard, Chinese herbs and herbal products have been considered a rich resource of product development. Although increasing evidence has been produced from various scientific studies, the mechanisms of action are lacking. Here, we have proposed that many herbal monomers and formulae improve glucose homeostasis and diabetes through the BMID axis; B represents gut microbiota, M means mucosal immunity, I represents inflammation, and D represents diabetes. Chinese herbs have been traditionally used to treat diabetes, with minimal side and toxic effects. Here, we reviewed monomers such as berberine, ginsenoside,

Topics: Animals; Berberine; Curcumin; Diabetes Mellitus, Type 2; Drugs, Chinese Herbal; Gastrointestinal Microbiome; Ginsenosides; Glucose; Humans; Immunity, Mucosal; Inflammation; Momordica charantia; Plant Extracts

Monocyte chemoattractant/chemotactic protein-1 (MCP-1), a member of the CC chemokine family, is one of the key chemokines that regulate migration and tissue infiltration of monocytes/macrophages. Its role in the pathophysiology of several inflammatory diseases has been widely recognized, thus making MCP-1 a possible target for anti-inflammatory treatments. Curcumin (diferuloylmethane) is a natural polyphenol derived from the rhizomes of Curcuma Longa L. (turmeric). Anti-inflammatory action underlies numerous pharmacological effects of curcumin in the control and prevention of several diseases. The purpose of this review is to evaluate the effects of curcumin on the regulation of MCP-1 as a key mediator of chemotaxis and inflammation, and the biological consequences thereof. In vitro studies have shown that curcumin can decrease MCP-1 production in various cell lines. Animal studies have also revealed that curcumin can attenuate MCP-1 expression and improve a range of inflammatory diseases through multiple molecular targets and mechanisms of action. There is limited data from human clinical trials showing the decreasing effect of curcumin on MCP-1 concentrations and improvement of the course of inflammatory diseases. Most of the in vitro and animal studies confirm that curcumin exert its MCP-1-lowering and anti-inflammatory effects by down-regulating the mitogen-activated protein kinase (MAPK) and NF-κB signaling pathway. As yet, there is limited data from human clinical trials showing the effect of curcumin on MCP-1 levels and improvement of the course of inflammatory diseases. More evidence, especially from human studies, is needed to better assess the effects of curcumin on circulating MCP-1 in different human diseases and the role of this modulatory effect in the putative anti-inflammatory properties of curcumin.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Atherosclerosis; Cell Line; Chemokine CCL2; Clinical Trials as Topic; Curcumin; Epilepsy; Gene Expression Regulation; Humans; Inflammation; MAP Kinase Signaling System; Mice; NF-kappa B; Osteoarthritis; Signal Transduction

Curcumin (diferuloylmethane) is a yellow pigment present in the spice turmeric (Curcuma longa). It has been used for centuries in Ayurveda (Indian traditional medicine) for the treatment of several diseases. Over the last several decades, the therapeutic properties of curcumin have slowly been elucidated. It has been shown that curcumin has pleiotropic effects, regulating transcription factors (e.g., NF-kB), cytokines (e.g., IL6, TNF-alpha), adhesion molecules (e.g., ICAM-1), and enzymes (e.g., MMPs) that play a major role in inflammation and cancerogenesis. These effects may be relevant for several pulmonary diseases that are characterized by abnormal inflammatory responses, such as asthma or chronic obstructive pulmonary disease, acute respiratory distress syndrome, pulmonary fibrosis, and acute lung injury. Furthermore, some preliminary evidence suggests that curcumin may have a role in the treatment of lung cancer. The evidence for the use of curcumin in pulmonary disease is still sparse and has mostly been obtained using either in vitro or animal models. The most important issue with the use of curcumin in humans is its poor bioavailability, which makes it necessary to use adjuvants or curcumin nanoparticles or liposomes. The aim of this review is to summarize the available evidence on curcumin's effectiveness in pulmonary diseases, including lung cancer, and to provide our perspective on future research with curcumin so as to improve its pharmacological effects, as well as provide additional evidence of curcumin's efficacy in the treatment of pulmonary diseases.

Topics: Animals; Curcumin; Humans; Inflammation; Lung Diseases

As a sugar additive, fructose is widely used in processed foods and beverages. Excessive fructose consumption can cause hepatic steatosis and dyslipidemia, leading to the development of metabolic syndrome. Recent research revealed that fructose-induced nonalcoholic fatty liver disease (NAFLD) is related to several pathological processes, including: (1) augmenting lipogenesis; (2) leading to mitochondrial dysfunction; (3) stimulating the activation of inflammatory pathways; and (4) causing insulin resistance. Cellular signaling research indicated that partial factors play significant roles in fructose-induced NAFLD, involving liver X receptor (LXR)α, sterol regulatory element binding protein (SREBP)-1/1c, acetyl-CoA carboxylase (ACC), fatty acid synthase (FAS), stearoyl-CoA desaturase (SCD), peroxisome proliferator-activated receptor α (PPARα), leptin nuclear factor-erythroid 2-related factor 2 (Nrf2), nuclear factor kappa B (NF-κB), tumor necrosis factor α (TNF-α), c-Jun amino terminal kinase (JNK), phosphatidylinositol 3-kinase (PI3K) and adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK). Until now, a series of natural products have been reported as regulators of NAFLD in vivo and in vitro. This paper reviews the natural products (e.g., curcumin, resveratrol, and (-)-epicatechin) and their mechanisms of ameliorating fructose-induced NAFLD over the past years. Although, as lead compounds, natural products usually have fewer activities compared with synthesized compounds, it will shed light on studies aiming to discover new drugs for NAFLD.

Topics: Animals; Biological Products; Catechin; Curcumin; Fructose; Humans; Inflammation; Insulin Resistance; Lipogenesis; Mitochondria; Non-alcoholic Fatty Liver Disease; Resveratrol; Stilbenes

Neuroinflammation is a pathophysiological process present in a number of neurodegenerative disorders, such as Alzheimer's disease, Huntington's disease, Parkinson's disease, stroke, traumatic brain injury including chronic traumatic encephalopathy and other age-related CNS disorders. Although there is still much debate about the initial trigger for some of these neurodegenerative disorders, during the progression of disease, broad range anti-inflammatory drugs including cytokine suppressive anti-inflammatory drugs (CSAIDs) might be promising therapeutic options to limit neuroinflammation and improve the clinical outcome. One of the most promising CSAIDs is curcumin, which modulates the activity of several transcription factors (e.g., STAT, NF-κB, AP-1) and their pro-inflammatory molecular signaling pathways. However, normal curcumin preparations demonstrate low bioavailability in vivo. To increase bioavailability, preparations of high bioavailability curcumin have been introduced to achieve therapeutically relevant concentrations in target tissues. This literature review aims to summarize the pharmacokinetic and toxicity profile of different curcumin formulations.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Biological Availability; Curcumin; Disease Progression; Humans; Inflammation; Neurodegenerative Diseases; Signal Transduction

Ferulic acid, a natural phytochemical has gained importance as a potential therapeutic agent by virtue of its easy commercial availability, low cost and minimal side-effects. It is a derivative of curcumin and possesses the necessary pharmacokinetic properties to be retained in the general circulation for several hours. The therapeutic effects of ferulic acid are mediated through its antioxidant and anti-inflammatory properties. It exhibits different biological activities such as anti-inflammatory, anti-apoptotic, anti-carcinogenic, anti-diabetic, hepatoprotective, cardioprotective, neuroprotective actions, etc. The current review addresses its therapeutic effects under different pathophysiological conditions (eg. cancer, cardiomyopathy, skin disorders, brain disorders, viral infections, diabetes etc.).

Topics: Alzheimer Disease; Animals; Anti-Inflammatory Agents, Non-Steroidal; Antioxidants; Apoptosis; Cardiomyopathies; Cell Differentiation; Coumaric Acids; Curcumin; Diabetes Complications; Humans; Inflammation; Parkinson Disease; Schwann Cells; Skin Diseases

Curcumin, which was first used 3000 years ago as an anti-inflammatory agent, is a well-known bioactive compound derived from the active ingredient of turmeric (Curcuma longa). Previous research has demonstrated that curcumin has immense therapeutic potential in a variety of diseases via anti-oxidative, anti-apoptotic, and anti-inflammatory pathways. Cardiac diseases are the leading cause of mortality worldwide and cause considerable harm to human beings. Numerous studies have suggested that curcumin exerts a protective role in the human body whereas its actions in cardiac diseases remain elusive and poorly understood. On the basis of the current evidence, we first give a brief introduction of cardiac diseases and curcumin, especially regarding the effects of curcumin in embryonic heart development. Secondly, we analyze the basic roles of curcumin in pathways that are dysregulated in cardiac diseases, including oxidative stress, apoptosis, and inflammation. Thirdly, actions of curcumin in different cardiac diseases will be discussed, as will relevant clinical trials. Eventually, we would like to discuss the existing controversial opinions and provide a detailed analysis followed by the remaining obstacles, advancement, and further prospects of the clinical application of curcumin. The information compiled here may serve as a comprehensive reference of the protective effects of curcumin in the heart, which is significant to the further research and design of curcumin analogs as therapeutic options for cardiac diseases.

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Cardiotonic Agents; Curcuma; Curcumin; Heart; Heart Diseases; Humans; Inflammation; Myocardium; Oxidative Stress

Accurate. Since sCD30 levels and sCD26/sCD30 ratios may contribute to the activity of the disease, they may be used to assess ITP disease activity.. hBMSCs and hFOB1.19 cells modulate the phenotype of PC3 prostate cancer cells and the expression of CD59 by activating the RANK/RANKL/OPG signaling pathway.. Results showed that the EEG responses at lower levels of the independent variables were significantly high than at higher levels; except for oxygen content, the EEG responses at lower levels were considerably lower than at a higher level. It also showed that an upsurge in the physical demand increased lifting frequency and replication and caused decreasing in alpha power, theta/beta, alpha/beta, (theta + alpha)/beta, (theta + alpha)/(alpha + beta) and increasing in the theta power and the gamma power. Furthermore, several interactions among independent variables had significant effects on the EEG responses.. The EEG implementation for the investigation of neural responses to physical demands allows for the possibility of newer nontraditional and faster methods of human performance monitoring. These methods provide effective and reliable results as compared to other traditional methods. This study will safeguard the physical capabilities and possible health risks of industrial workers. And the applications of these tasks can occur in almost all working environments (factories, warehouses, airports, building sites, farms, hospitals, offices, etc.) that are at high altitudes. It can include lifting boxes at a packaging line, handling construction materials, handling patients in hospitals, and cleaning.

Topics: Action Potentials; Adolescent; Adult; Aged; Alanine Transaminase; Analgesics; Animals; Anti-Inflammatory Agents; Antineoplastic Agents; Antioxidants; Apoptosis; Arrhythmias, Cardiac; Atrial Fibrillation; Biological Transport; Biomarkers; Blood Gas Analysis; Blood-Brain Barrier; Blotting, Western; Bone and Bones; Bone Marrow; Bone Neoplasms; Brain; Breast Neoplasms; Calcium; Carbon Tetrachloride; Cartilage, Articular; Case-Control Studies; CD59 Antigens; CDC2 Protein Kinase; Celastrus; Cell Cycle; Cell Division; Cell Line; Cell Line, Tumor; Cell Proliferation; Cell Survival; Chemical Fractionation; Colitis, Ulcerative; Colon; Computer Simulation; Curcumin; Cyclin B1; Cymenes; Cytokines; Dextran Sulfate; Dipeptidyl Peptidase 4; Disease Models, Animal; Disease Progression; Dose-Response Relationship, Drug; Ectodysplasins; Electroencephalography; Endothelial Cells; Epithelial Cells; Epithelial-Mesenchymal Transition; Exosomes; Female; Flavonoids; G2 Phase; Gene Expression Regulation; Glial Cell Line-Derived Neurotrophic Factor; Heart Atria; Heart Conduction System; Heart Ventricles; HeLa Cells; Hemodynamics; Humans; Image Interpretation, Computer-Assisted; Indoles; Inflammation; Interleukin-1beta; Interleukin-6; Iridoid Glycosides; Ki-1 Antigen; Lens, Crystalline; Lifting; Liver; Liver Cirrhosis; Male; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Inbred ICR; Microelectrodes; Middle Aged; Models, Cardiovascular; Multiparametric Magnetic Resonance Imaging; Myeloid Differentiation Factor 88; NADPH Oxidase 1; Neoplasm Grading; NF-kappa B; Osteoarthritis; Osteoblasts; Osteoclasts; Oxidative Stress; Oxygen; Patch-Clamp Techniques; PC-3 Cells; Permeability; Peroxidase; Plant Extracts; Plant Leaves; Prostate; Prostatic Neoplasms; Protective Agents; Proto-Oncogene Proteins c-akt; Psychophysics; Purpura, Thrombocytopenic, Idiopathic; Rabbits; Rats; Rats, Sprague-Dawley; Recovery of Function; Retrospective Studies; RNA, Long Noncoding; ROC Curve; Safety; Shoes; Signal Transduction; Sodium; Sonication; Spinal Cord; Spinal Cord Injuries; Syringa; Tight Junctions; Tissue Inhibitor of Metalloproteinase-1; Toll-Like Receptor 2; Transforming Growth Factor beta2; Transient Receptor Potential Channels; Tumor Microenvironment; Tumor Necrosis Factor-alpha; Umbilical Cord; Up-Regulation; Ventricular Function; Young Adult

Alzheimer's disease (AD) is a progressive neurodegenerative disorder, characterized by deposition of amyloid plaques and neurofibrillary tangles, as well as microglial and astroglial activation, and, finally, leading to neuronal dysfunction and death. Current treatments for AD primarily focus on enhancement of cholinergic transmission. However, these treatments are only symptomatic, and no disease-modifying drug is available for the treatment of AD patients. This review will provide an overview of the antioxidant, anti-inflammatory, anti-amyloidogenic, neuroprotective, and cognition-enhancing effects of a variety of nutraceuticals including curcumin, apigenin, docosahexaenoic acid, epigallocatechin gallate, α-lipoic acid and resveratrol and their potential for AD prevention and treatment. We suggest that therapeutic use of these compounds might lead to a safe strategy to delay the onset of AD or slow down its progression. The continuing investigation of the potential of these substances is necessary as they are promising compounds to yield a possible remedy for this pervasive disease.

Topics: Alzheimer Disease; Animals; Antioxidants; Biological Products; Chronic Disease; Curcumin; Fish Oils; Humans; Inflammation; Neurodegenerative Diseases; Neurofibrillary Tangles; Neuroprotective Agents; Randomized Controlled Trials as Topic; Resveratrol; Stilbenes

Nowadays, there are some molecules that have shown over the years a high capacity to act against relevant pathologies such as cardiovascular disease, neurodegenerative disorders or cancer. This article provides a brief review about the origin, bioavailability and new research on curcumin and synthetized derivatives. It examines the beneficial effects on health, delving into aspects such as cancer, cardiovascular effects, metabolic syndrome, antioxidant capacity, anti-inflammatory properties, and neurological, liver and respiratory disorders. Thanks to all these activities, curcumin is positioned as an interesting nutraceutical. This is the reason why it has been subjected to several modifications in its structure and administration form that have permitted an increase in bioavailability and effectiveness against different diseases, decreasing the mortality and morbidity associated to these pathologies.

Topics: Animals; Anti-Inflammatory Agents; Antineoplastic Agents, Phytogenic; Antioxidants; Biological Availability; Cardiotonic Agents; Cardiovascular Diseases; Curcuma; Curcumin; Humans; Inflammation; Neoplasms; Neurodegenerative Diseases; Neuroprotective Agents; Plants, Medicinal

The aim of this meta-analysis was to evaluate the efficacy of curcuminoids supplementation on circulating concentrations of IL-6 in randomized controlled trials (RCTs). The search included PubMed-Medline, Scopus, Web of Science and Google Scholar databases by up to November 01, 2015, to identify RCTs investigating the impact of curcuminoids on circulating IL-6 concentrations. Nine RCTs comprising 10 treatment arms were found to be eligible for the meta-analysis. There was a significant reduction of circulating IL-6 concentrations following curcuminoids supplementation (WMD: -0.60pg/mL, 95% CI: -1.06, -0.14, p=0.011). Meta-regression did not suggest any significant association between the circulating IL-6 lowering effects of curcuminoids with either dose or duration of treatment. There was a significant association between the IL-6-lowering activity of curcumin and baseline IL-6 concentration (slope: -0.51; 95% CI: -0.80, -0.23; p=0.005). This meta-analysis of RCTs suggested a significant effect of curcumin in lowering circulating IL-6 concentrations. This effect appears to be more evident in patients with higher degrees of systemic inflammation.

Topics: Adult; Aged; Anti-Inflammatory Agents; Biomarkers; Curcumin; Down-Regulation; Female; Humans; Inflammation; Inflammation Mediators; Interleukin-6; Male; Middle Aged; Randomized Controlled Trials as Topic; Treatment Outcome

Curcumin is the major polyphenolic constituent of an indigenous herb, Curcuma longa, found to have a wide range of applications right from its kitchen use as a spicy ingredient to therapeutic and medicinal applications in various diseases. Curcumin has been identified to have a plethora of biologic and pharmacologic properties owing to its antioxidant and anti-inflammatory activities. This pleiotropic regulation of redox balance of cell and inflammation might be the basis of curcumin's beneficial activities in various pathologic conditions including diabetic complications. This review summarizes various in vitro, in vivo studies done on curcumin and its therapeutic utility in diabetic micro-vascular complications. This review also emphasizes the importance of curcumin in addition to the existing therapeutic modalities in diabetic complications.

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Curcumin; Diabetes Complications; Disease Models, Animal; Humans; Inflammation; Phytochemicals; Spices

Curcumin (1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione) is commonly used as a spice, food additive or dietary pigment. Accumulating evidence suggests that curcumin has several pharmacologic effects, including anti-inflammatory, anti-oxidant and anti-cancer activities. The molecular mechanisms underlying the targets of curcumin are diverse and involve combinations of multiple signaling pathways, including NF-κB and STAT3 signaling. Thus, curcumin is one of the most promising phytochemicals that target various cancers and inflammation-mediated diseases. Clinical trials have been ongoing or completed for various cancers, including breast, pancreatic and colorectal cancers, and multiple myeloma. In this review, the molecular mechanisms and the issue of bioavailability are mainly discussed.

Topics: Animals; Anti-Inflammatory Agents; Antineoplastic Agents, Phytogenic; Biological Availability; Curcumin; Humans; Inflammation; Inflammation Mediators; Molecular Targeted Therapy; Neoplasms; Signal Transduction

It is extensively verified that continued oxidative stress and oxidative damage may lead to chronic inflammation, which in turn can mediate most chronic diseases including cancer, diabetes, cardiovascular, neurological, inflammatory bowel disease and pulmonary diseases. Curcumin, a yellow coloring agent extracted from turmeric, shows strong anti-oxidative and anti-inflammatory activities when used as a remedy for the prevention and treatment of chronic diseases. How oxidative stress activates inflammatory pathways leading to the progression of chronic diseases is the focus of this review. Thus, research to date suggests that chronic inflammation, oxidative stress, and most chronic diseases are closely linked, and the antioxidant properties of curcumin can play a key role in the prevention and treatment of chronic inflammation diseases.

Topics: Anti-Inflammatory Agents; Antioxidants; Chronic Disease; Curcumin; Humans; Inflammation; Medicine, Chinese Traditional; Oxidation-Reduction; Oxidative Stress

It has a great therapeutic significance that the disorder of the vascular endothelium, which supplies the affected ocular structures, plays a major role in the development of age-related macular degeneration. Chronic inflammation is closely linked to diseases associated with endothelial dysfuncition and age-related macular degeneration is accompanied by a general inflammatory response. The vascular wall including those in chorioids may be activated by several repeated and/or prolonged mechanical, physical, chemical, microbiological, immunologic and genetic factors causing a protracted host defence response with a consequent vascular damage, which leads to age-related macular degeneration. Based on this concept, age-related macular degeneration is a local manifestation of the systemic vascular disease. This recognition should have therapeutic implications because restoration of endothelial dysfunction can stabilize the condition of chronic vascular disease including age-related macular degeneration, as well. Restoration of endothelial dysfunction by non-pharmacological or pharmacological interventions may prevent the development or improve endothelial dysfunction resulting in prevention or improvement of age-related macular degeneration. Non-pharmacological interventions which may have beneficial effect in endothelial dysfunction include (1) smoking cessation; (2) reduction of increased body weight; (3) adequate physical activity; (4) appropriate diet (a) proper dose of flavonoids, polyphenols and kurcumin; (b) omega-3 long-chain polyunsaturated fatty acids: docosahexaenoic acid and eicosapentaenoic acid; (c) carotenoids, lutein and zeaxanthins), (d) management of dietary glycemic index, (e) caloric restriction, and (5) elimination of stressful lifestyle. Non-pharmacological interventions should be preferable even if medicaments are also used for the treatment of endothelial dysfunction.

Topics: Aged; Aged, 80 and over; Anti-Inflammatory Agents, Non-Steroidal; Caloric Restriction; Carotenoids; Curcumin; Endothelium, Vascular; Fatty Acids, Omega-3; Feeding Behavior; Flavonoids; Glycemic Index; Humans; Inflammation; Lutein; Macular Degeneration; Motor Activity; Polyphenols; Risk Reduction Behavior; Smoking Cessation; Stress, Psychological; Weight Loss; Zeaxanthins

Curcumin, commonly known as turmeric, is a spice that comes from the root Curcuma longa. The present article presents an update of new studies of curcumin activities as tested in anticancer models from 2011 to 2015.. Evidence from in-vitro and in-vivo research, together with clinical trials conducted over the past few decades, substantiates the potential of curcumin as an anticancer and anti-inflammatory agent. The development of formulations of curcumin in the form of nanoparticles, liposomes, micelles, or phospholipid complexes to enhance its bioavailability and efficacy are still in the early stages. Clinical trials with curcumin indicate safety, tolerability, and nontoxicity. However, the efficacy is questionable, based on the small numbers of patients in each study.. The laboratory and the clinical studies until 2011 were summarized in a review published in this journal. An update of the new studies and knowledge from 2011 to March 2015 focuses on new ways to overcome its low bioavailability and data from clinical trials.

Topics: Anti-Inflammatory Agents; Antineoplastic Agents, Phytogenic; Curcuma; Curcumin; Functional Food; Humans; Inflammation; Neoplasms; Plant Extracts

Chronic viral infections like those caused by hepatitis C virus (HCV) and human immunodeficiency virus (HIV) cause disease that establishes an ongoing state of chronic inflammation. While there have been tremendous improvements towards curing HCV with directly acting antiviral agents (DAA) and keeping HIV viral loads below detection with antiretroviral therapy (ART), there is still a need to control inflammation in these diseases. Recent studies indicate that many natural products like curcumin, resveratrol and silymarin alter cellular metabolism and signal transduction pathways via enzymes such as adenosine monophosphate kinase (AMPK) and mechanistic target of rapamycin (mTOR), and these pathways directly influence cellular inflammatory status (such as NF-κB) and immune function. Natural products represent a vast toolkit to dissect and define how cellular metabolism controls cellular immune and inflammatory function.

Topics: Biological Products; Chronic Disease; Curcumin; Hepatitis C; HIV Infections; Humans; Immunity, Cellular; Immunologic Factors; Inflammation; Resveratrol; Silymarin; Stilbenes

Over 35 years research on PAKs, RAC/CDC42(p21)-activated kinases, comes of age, and in particular PAK1 has been well known to be responsible for a variety of diseases such as cancer (mainly solid tumors), Alzheimer's disease, acquired immune deficiency syndrome and other viral/bacterial infections, inflammatory diseases (asthma and arthritis), diabetes (type 2), neurofibromatosis, tuberous sclerosis, epilepsy, depression, schizophrenia, learning disability, autism, etc. Although several distinct synthetic PAK1-blockers have been recently developed, no FDA-approved PAK1 blockers are available on the market as yet. Thus, patients suffering from these PAK1-dependent diseases have to rely on solely a variety of herbal therapeutics such as propolis and curcumin that block PAK1 without affecting normal cell growth. Furthermore, several recent studies revealed that some of these herbal therapeutics significantly extend the lifespan of nematodes (C. elegans) and fruit flies (Drosophila), and PAK1-deficient worm lives longer than the wild type. Here, I outline mainly pathological phenotypes of hyper-activated PAK1 and a list of herbal therapeutics that block PAK1, but cause no side (harmful) effect on healthy people or animals.

Topics: Animals; Antineoplastic Agents, Phytogenic; Communicable Diseases; Curcumin; Humans; Inflammation; Longevity; Neoplasms; p21-Activated Kinases; Phytotherapy; Plants, Medicinal; Propolis

Many diseases have been described to be associated with inflammatory processes. The currently available anti-inflammatory drug therapy is often not successful or causes intolerable side effects. Thus, new anti-inflammatory substances are still urgently needed. Plants were the first source of remedies in the history of mankind. Since their chemical characterization in the 19th century, herbal bioactive compounds have fueled drug development. Also, nowadays, new plant-derived agents continuously enrich our drug arsenal (e.g., vincristine, galantamine, and artemisinin). The number of new, pharmacologically active herbal ingredients, in particular that of anti-inflammatory compounds, rises continuously. The major obstacle in this field is the translation of preclinical knowledge into evidence-based clinical progress. Human trials of good quality are often missing or, when available, are frequently not suitable to really prove a therapeutical value. This minireview will summarize the current situation of 6 very prominent plant-derived anti-inflammatory compounds: curcumin, colchicine, resveratrol, capsaicin, epigallocatechin-3-gallate (EGCG), and quercetin. We will highlight their clinical potential and/or pinpoint an overestimation. Moreover, we will sum up the planned trials in order to provide insights into the inflammatory disorders that are hypothesized to be beneficially influenced by the compound.

Topics: Animals; Anti-Inflammatory Agents; Capsaicin; Catechin; Colchicine; Curcumin; Humans; Imidazoles; Inflammation; Niacin; Resveratrol; Stilbenes

Turmeric (Curcuma longa) is a popular Indian spice that has been used for centuries in herbal medicines for the treatment of a variety of ailments such as rheumatism, diabetic ulcers, anorexia, cough and sinusitis. Curcumin (diferuloylmethane) is the main curcuminoid present in turmeric and responsible for its yellow color. Curcumin has been shown to possess significant anti-inflammatory, anti-oxidant, anti-carcinogenic, anti-mutagenic, anti-coagulant and anti-infective effects. Curcumin has also been shown to have significant wound healing properties. It acts on various stages of the natural wound healing process to hasten healing. This review summarizes and discusses recently published papers on the effects of curcumin on skin wound healing. The highlighted studies in the review provide evidence of the ability of curcumin to reduce the body's natural response to cutaneous wounds such as inflammation and oxidation. The recent literature on the wound healing properties of curcumin also provides evidence for its ability to enhance granulation tissue formation, collagen deposition, tissue remodeling and wound contraction. It has become evident that optimizing the topical application of curcumin through altering its formulation is essential to ensure the maximum therapeutical effects of curcumin on skin wounds.

Topics: Administration, Cutaneous; Animals; Collagen; Curcuma; Curcumin; Humans; Inflammation; Skin; Wound Healing

Curcumin is a natural product with several thousand years of heritage. Its traditional Asian application to human ailments has been subjected in recent decades to worldwide pharmacological, biochemical and clinical investigations. Curcumin's Achilles heel lies in its poor aqueous solubility and rapid degradation at pH ~ 7.4. Researchers have sought to unlock curcumin's assets by chemical manipulation. One class of molecules under scrutiny are the monocarbonyl analogs of curcumin (MACs). A thousand plus such agents have been created and tested primarily against cancer and inflammation. The outcome is clear. In vitro, MACs furnish a 10-20 fold potency gain vs. curcumin for numerous cancer cell lines and cellular proteins. Similarly, MACs have successfully demonstrated better pharmacokinetic (PK) profiles in mice and greater tumor regression in cancer xenografts in vivo than curcumin. The compounds reveal limited toxicity as measured by murine weight gain and histopathological assessment. To our knowledge, MAC members have not yet been monitored in larger animals or humans. However, Phase 1 clinical trials are certainly on the horizon. The present review focuses on the large and evolving body of work in cancer and inflammation, but also covers MAC structural diversity and early discovery for treatment of bacteria, tuberculosis, Alzheimer's disease and malaria.

Topics: Animals; Crystallography, X-Ray; Curcumin; Humans; Inflammation; Mice; Molecular Mimicry; Neoplasms

Curcumin is a principal polyphenolic curcuminoid extracted from turmeric rhizome, which has been used for treating inflammation of joints, ulcers, jaundice and other disorders in Asian traditional medicine. In recent years, many studies have indicated that curcumin plays important roles in treatment of liver diseases. Curcumin attenuates liver injury and non-alcoholic fatty liver disease by lowering the release of inflammation cytokines, minimizing oxidative stress, enhancing the sensitivity of insulin and altering lipid metabolism. Curcumin shows potent anti-fibrosis activity, contributing to inhibit the activation of hepatic stellate cells and reduce the deposition of extracellular matrix by its regulation of PPAR-γ, NF-ΚB and TGF-β signaling pathways. Moreover, curcumin exhibits anti-cancer effect by inducing G2/M phase cell cycle arrest and apoptosis in several hepatoma cell lines. However, poor water solubility and low bioavailability of curcumin limit its clinical applications. To overcome its limited systemic bioavailability, many new approaches have been explored to deliver curcumin effectively. This article focuses on advances in the effects of curcumin and its derivatives for treatment of liver injury, non-alcoholic fatty liver disease, liver fibrosis and hepatocarcinoma.

Topics: Apoptosis; Cell Cycle Checkpoints; Cell Line, Tumor; Curcumin; Hepatic Stellate Cells; Humans; Inflammation; Liver Diseases; NF-kappa B; Oxidative Stress; PPAR gamma; Signal Transduction; Transforming Growth Factor beta

Curcumin, the major extraction of turmeric, has been widely used in many countries for centuries both as a spice and as a medicine. In the last decade, researchers have found the beneficial effects of curcumin on multiple disorders are due to its antioxidative, anti-inflammatory, and antiproliferative properties, as well as its novel function as an inhibitor of histone aectyltransferases. In this review, we summarize the recent progress made on studying the beneficial effects of curcumin on multiple retinal diseases, including diabetic retinopathy, glaucoma, and age-related macular degeneration. Recent clinical trials on the effectiveness of phosphatidylcholine formulated curcumin in treating eye diseases have also shown promising results, making curcumin a potent therapeutic drug candidate for inflammatory and degenerative retinal and eye diseases.

Topics: Animals; Anti-Inflammatory Agents; Clinical Trials as Topic; Curcuma; Curcumin; Diabetic Retinopathy; Disease Models, Animal; Glaucoma; Humans; Inflammation; Macular Degeneration; Retinal Diseases; Retinitis Pigmentosa; Retinoblastoma; Vitreoretinopathy, Proliferative

TNFs are major mediators of inflammation and inflammation-related diseases, hence, the United States Food and Drug Administration (FDA) has approved the use of blockers of the cytokine, TNF-α, for the treatment of osteoarthritis, inflammatory bowel disease, psoriasis and ankylosis. These drugs include the chimeric TNF antibody (infliximab), humanized TNF-α antibody (Humira) and soluble TNF receptor-II (Enbrel) and are associated with a total cumulative market value of more than $20 billion a year. As well as being expensive ($15 000-20 000 per person per year), these drugs have to be injected and have enough adverse effects to be given a black label warning by the FDA. In the current report, we describe an alternative, curcumin (diferuloylmethane), a component of turmeric (Curcuma longa) that is very inexpensive, orally bioavailable and highly safe in humans, yet can block TNF-α action and production in in vitro models, in animal models and in humans. In addition, we provide evidence for curcumin's activities against all of the diseases for which TNF blockers are currently being used. Mechanisms by which curcumin inhibits the production and the cell signalling pathways activated by this cytokine are also discussed. With health-care costs and safety being major issues today, this golden spice may help provide the solution.. This article is part of a themed section on Emerging Therapeutic Aspects in Oncology. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2013.169.issue-8.

Topics: Animals; Biological Availability; Curcumin; Disease Models, Animal; Humans; Inflammation; Receptors, Tumor Necrosis Factor; Tumor Necrosis Factor-alpha

Type 2 diabetes is a chronic condition in which cells have reduced insulin signalling, leading to hyperglycemia and long-term complications, including heart, kidney and liver disease. Macrophages activated by dying or stressed cells, induce the transcription factor nuclear factor kappa-B leading to the production of pro-inflammatory cytokines including TNF and IL-6. These inflammatory macrophages in liver and adipose tissue promote insulin resistance, and medications which reduce inflammation and enhance insulin signalling improve glucose control. Curcumin is an anti-oxidant and nuclear factor kappa-B inhibitor derived from turmeric. A number of studies have shown that dietary curcumin reduces inflammation and delays or prevents obesity-induced insulin resistance and associated complications, including atherosclerosis and immune mediate liver disease. Unfortunately dietary curcumin is poorly absorbed by the digestive system and undergoes glucuronidation and excretion rather than being released into the serum and systemically distributed. This confounds understanding of how dietary curcumin exerts its beneficial effects in type 2 diabetes and associated diseases. New improved methods of delivering curcumin are being developed including nanoparticles and lipid/liposome formulations that increase absorption and bioavailability of curcumin. Development and refinement of these technologies will enable cell-directed targeting of curcumin and improved therapeutic outcome.

Topics: Adipose Tissue; Animals; Curcuma; Curcumin; Diabetes Mellitus, Type 2; Disease Models, Animal; Drug Delivery Systems; Humans; I-kappa B Proteins; Inflammation; Insulin; Insulin Resistance; Liver; Liver Diseases; Nanoparticles; NF-kappa B; NF-KappaB Inhibitor alpha; Obesity; Randomized Controlled Trials as Topic

Adipose tissue has an important endocrine function in the regulation of whole-body metabolism. Obesity leads to a chronic low-grade inflammation of the adipose tissue, which disrupts this endocrine function and results in metabolic derangements, such as type-2 diabetes. Dietary bioactive compounds, such as polyphenols and certain fatty acids, are known to suppress both systemic and adipose tissue inflammation and have the potential to improve these obesity-associated metabolic disorders. Mechanistically, polyphenolic compounds including non-flavonoids, such as curcumin and resveratrol, and flavonoids, such as catechins (tea-polyphenols), quercetin and isoflavones, suppress nuclear factor-κB (NF-κB) and mitogen-activated protein (MAP) kinases (MAPK) pathways while activating the 5' adenosine monophosphate-activated protein kinase (AMPK) pathway in adipose tissue. Dietary polyunsaturated fatty acids, such as eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), conjugated linoleic acid (CLA) and monounsaturated fatty acids (MUFA), such as oleic acid, also impart anti-inflammatory effects through several mechanisms. These include activation of AMPK and peroxisome proliferator-activated receptor gamma (PPAR-γ), as well as suppression of toll-like receptors (TLRs) and NF-κB pathway. This review discusses the major molecular mechanisms of dietary polyphenols and fatty acids, alone or in combination, which are responsible for adipose tissue-associated anti-inflammatory effects.

Topics: Adipose Tissue; Curcumin; Endocrine Glands; Fatty Acids; Food; Humans; Inflammation; Insulin Resistance; Polyphenols; Quercetin; Resveratrol; Stilbenes

Turmeric, a dried powder derived from the rhizome of Curcuma longa, has been used for centuries in certain parts of the world and has been linked to numerous biological activities including antioxidant, anti-inflammatory, anticancer, antigrowth, anti-arthritic, anti-atherosclerotic, antidepressant, anti-aging, antidiabetic, antimicrobial, wound healing, and memory-enhancing activities. One component of turmeric is curcumin, which has been extensively studied, as indicated by more than 5600 citations, most of which have appeared within the past decade. Recent research has identified numerous chemical entities from turmeric other than curcumin. It is unclear whether all of the activities ascribed to turmeric are due to curcumin or whether other compounds in turmeric can manifest these activities uniquely, additively, or synergistically with curcumin. However, studies have indicated that turmeric oil, present in turmeric, can enhance the bioavailability of curcumin. Studies over the past decade have indicated that curcumin-free turmeric (CFT) components possess numerous biological activities including anti-inflammatory, anticancer, and antidiabetic activities. Elemene derived from turmeric is approved in China for the treatment of cancer. The current review focuses on the anticancer and anti-inflammatory activities exhibited by CFT and by some individual components of turmeric, including turmerin, turmerone, elemene, furanodiene, curdione, bisacurone, cyclocurcumin, calebin A, and germacrone.

Topics: Animals; Anti-Inflammatory Agents; Antineoplastic Agents; Antioxidants; Clinical Trials as Topic; Curcuma; Curcumin; Cyclohexanols; Disease Models, Animal; Furans; Heterocyclic Compounds, 2-Ring; Humans; Hypoglycemic Agents; Inflammation; Neoplasms; Sesquiterpenes; Sesquiterpenes, Germacrane

The aim of this systematic review is to summarize the evidence for or against the efficacy of plant food supplements (PFS) for coping inflammatory conditions by considering epidemiological and human intervention studies. The review considers six botanical species commonly used as food supplements/medicinals: Urtica dioica L., Symphytum officinalis L., Calendula officinalis L., Curcuma longa L., Boswellia serrata Roxb., and Harpagophytum procumbens L. The search retrieved 579 publications. By removing the duplicates and applying the inclusion/exclusion criteria, the final number of papers was 47. No epidemiological data were found. The bibliographic search found no paper regarding the anti-inflammatory effects of Calendula officinalis L. and Symphytum officinalis L. by oral use. In spite of the long-term traditional use for inflammatory disorders, Curcuma longa L. and Harpagophytum procumbens L. warrant further investigation, whereas the efficacy of Urtica dioica L, even if the available data on hard endpoints are promising, requires other trials. Boswellia serrata Roxb. was found to be the most promising, since it shows the best efficacy for the treatment of pain/inflammatory conditions. In conclusion, it is advisable to conduct further studies with more homogeneous population and larger number of subjects by avoiding the heterogeneity of the herbal preparations considered.

Topics: Anti-Inflammatory Agents; Boswellia; Curcuma; Dietary Supplements; Harpagophytum; Humans; Inflammation; Phytotherapy; Plant Preparations; Randomized Controlled Trials as Topic; Urtica dioica

Interleukin 1β (IL-1β) and tumor necrosis factor α (TNF-α) are key cytokines that drive the production of inflammatory mediators and matrix-degrading enzymes in osteoarthritis (OA). These proinflammatory cytokines bind to their respective cell surface receptors and activate inflammatory signaling pathways culminating with the activation of nuclear factor κB (NF-κB), a transcription factor that can be triggered by a host of stress-related stimuli including, excessive mechanical stress and ECM degradation products. Once activated, NF-κB regulates the expression of many cytokines, chemokines, adhesion molecules, inflammatory mediators, and several matrix-degrading enzymes. Therefore, proinflammatory cytokines, their cell surface receptors, NF-κB and downstream signaling pathways are therapeutic targets in OA. This paper critically reviews the recent literature and outlines the potential prophylactic properties of plant-derived phytochemicals such as curcumin and resveratrol for targeting NF-κB signaling and inflammation in OA to determine whether these phytochemicals can be used as functional foods.

Topics: Angiogenesis Inhibitors; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Cartilage, Articular; Chondrocytes; Curcumin; Humans; Inflammation; Interleukin-1beta; Joints; Osteoarthritis; Phytochemicals; Phytotherapy; Resveratrol; Stilbenes; Transcription Factor RelA; Tumor Necrosis Factor-alpha

Over the last decades there has been an increasing interest in a possible role of curcumin on cancer. Although curcumin is considered safe for healthy people, conclusive evidence on the safety and efficacy of curcumin for patients with monoclonal gammopathies is, so far, lacking. The present paper reviews the literature on molecular, cellular and clinical effects of curcumin in an attempt to identify, reasons for optimism but also for concern. The results of this critical evaluation can be useful for both patient- selection and monitoring in the context of clinical trials. Curcumin might be helpful for some but certainly not for all patients with monoclonal gammopathies. It is important to avoid unnecessary detrimental side effects in some in order to safeguard curcumin for those that could benefit. Parameters for patient monitoring, that can be used as early warning signs and as indicators of a favorable development have therefore been suggested.

Topics: Bone Marrow; Curcumin; Humans; Immune System; Inflammation; Monoclonal Gammopathy of Undetermined Significance; Paraproteinemias

Mesenchymal stem cells (MSCs) are one subgroup of adult stem cells and possess a proliferative potential and ability to differentiate into various ceells.. Emerging evidence suggests that MSCs can reprogram toward cancer stem cells (CSCs), due to alterations of intrinsic and extrinsic microenvironments, leading to tumorigenesis. The CSC concept has fundamental clinical implications because of its involvement in cell migration/invasion, metastasis, and treatment resistance. Therefore, targeting CSCs provides a novel therapeutic strategy for cancer treatment. However, the origin of CSCs and its molecular connections are not fully understood. Emerging evidence suggests the existence of an inter-relationship between CSCs and epithelial-to-mesenchymal transition (EMT) phenotypic cells, in the context of inflammation and hypoxia, as well as the potential role of miRNAs.. We suggest that targeting CSC signatures along with EMT, inflammation, and hypoxia will provide a more effective therapeutic approach for the elimination of CSCs. To that end, curcumin especially its synthetic novel analog CDF have been shown to attenuate CSC characteristics along with the deregulation of multiple pathways and miRNAs, leading to the inhibition of human tumor growth in vivo, suggesting the potential role of CDF as an anti-tumor agent for the prevention/treatment of tumor progression.

Topics: Animals; Antineoplastic Agents; Cell Hypoxia; Curcumin; Epithelial-Mesenchymal Transition; Humans; Inflammation; Mesenchymal Stem Cells; MicroRNAs; Neoplasms; Neoplastic Stem Cells; Tumor Microenvironment

Curcumin, a natural yellow pigment of turmeric, has become focus of interest with regard to its role in regulation of matrix metalloproteinases (MMPs). MMPs are metal-dependent endopeptidases capable of degrading components of the extracellular matrix. MMPs are involved in chronic diseases such as arthritis, Alzheimer's disease, psoriasis, chronic obstructive pulmonary disease, asthma, cancer, neuropathic pain, and atherosclerosis.. Curcumin regulates the expression and secretion of various MMPs. This review documents the matrix metalloproteinase inhibitory activity of curcumin on various diseases viz., cancer, arthritis, and ulcer. Finally, the steps to be taken for getting potent curcuminoids have also been discussed in the structure-activity relationship (SAR) section. From this review, readers can get answer to the question: Is curcumin a potential MMPI candidate?. Numerous approaches have been taken to beget a molecule with specificity restricted to a particular MMP as well as good oral bioavailability; however, nearly all the molecules lack these criteria. Using quantitative structure-activity relationship (QSAR) modeling and virtual screening, new analogs of curcumin can be designed which will be selectively inhibiting different MMPs.

Topics: Animals; Curcumin; Humans; Inflammation; Matrix Metalloproteinase Inhibitors; Matrix Metalloproteinases; Neoplasms; Structure-Activity Relationship

Multiple sclerosis (MS) is a chronic inflammatory autoimmune disease of the central nervous system (CNS). It is associated with a variety of pathophysiological features, including breakdown of the blood-brain barrier (BBB), autoimmune attack, injury of axons and myelin sheaths. Th17 cells are considered as a key immunological player for the pathophysiological process of MS. Neuroprotective approaches work best prior to the initiation of damage, suggesting that some safe and effective prophylaxis would be highly desirable. Curcumin, a dietary spice from turmeric, has outstanding anti-inflammation and neuroprotective effects. Herein, we review key features of curcumin involved biology, pharmacology, and medicinal chemistry and discuss its potential relevance to pathophysiological progress of MS.

Topics: Anti-Inflammatory Agents; Curcumin; Humans; Inflammation; Multiple Sclerosis

Inflammation is a disease of vigorous uncontrolled activated immune responses. Overwhelming reports have suggested that the modulation of immune responses by curcumin plays a dominant role in the treatment of inflammation and metabolic diseases. Observations from both in-vitro and in-vivo studies have provided strong evidence towards the therapeutic potential of curcumin. These studies have also identified a plethora of biological targets and intricate mechanisms of action that characterize curcumin as a potent 'drug' for numerous ailments. During inflammation the functional influence of lymphocytes and the related cross-talk can be modulated by curcumin to achieve the desired immune status against diseases. This review describes the regulation of immune responses by curcumin and effectiveness of curcumin in treatment of diseases of diverse nature.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Autoimmune Diseases; Curcumin; Humans; Hypersensitivity; Inflammation; Molecular Structure

Curcumin (diferuloylmethane), an orange-yellow component of turmeric or curry powder, is a polyphenol natural product isolated from the rhizome of the plant Curcuma longa. For centuries, curcumin has been used in some medicinal preparation or used as a food-coloring agent. In recent years, extensive in vitro and in vivo studies suggested curcumin has anticancer, antiviral, antiarthritic, anti-amyloid, antioxidant, and anti-inflammatory properties. The underlying mechanisms of these effects are diverse and appear to involve the regulation of various molecular targets, including transcription factors (such as nuclear factor-kB), growth factors (such as vascular endothelial cell growth factor), inflammatory cytokines (such as tumor necrosis factor, interleukin 1 and interleukin 6), protein kinases (such as mammalian target of rapamycin, mitogen-activated protein kinases, and Akt) and other enzymes (such as cyclooxygenase 2 and 5 lipoxygenase). Thus, due to its efficacy and regulation of multiple targets, as well as its safety for human use, curcumin has received considerable interest as a potential therapeutic agent for the prevention and/or treatment of various malignant diseases, arthritis, allergies, Alzheimer's disease, and other inflammatory illnesses. This review summarizes various in vitro and in vivo pharmacological aspects of curcumin as well as the underlying action mechanisms. The recently identified molecular targets and signaling pathways modulated by curcumin are also discussed here.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Curcumin; Humans; Inflammation; Molecular Targeted Therapy

Yes, but data aren't plentiful. Limited evidence suggests that turmeric and its active compound, curcumin, are effective for rheumatoid arthritis and other inflammatory conditions (strength of recommendation [SOR]: C, primarily low-quality cohort studies with small patient numbers). Curcumin has shown limited benefit for patients with psoriasis, inflammatory bowel disease (IBS), inflammatory eye diseases, familial adenomatous polyposis, and kidney transplantation (SOR: B, small, short randomized controlled trials [RCTs]). No evidence indicates that curcumin helps patients with human immunodeficiency virus (HIV) (SOR: B, single RCT).

Topics: Anti-Inflammatory Agents, Non-Steroidal; Curcumin; Evidence-Based Medicine; Humans; Inflammation; Practice Guidelines as Topic; Randomized Controlled Trials as Topic; Treatment Outcome

Oxidative damage and inflammation have been pointed out in preclinical studies as the root cause of cancer and other chronic diseases such as diabetes, hypertension, Alzheimer's disease, etc. Epidemiological and clinical studies have suggested that cancer could be prevented or significantly reduced by treatment with anti-oxidant and anti-inflammatory drugs, therefore, curcumin, a principal component of turmeric (a curry spice) showing strong anti-oxidant and anti-inflammatory activities, might be a potential candidate for the prevention and/or treatment of cancer and other chronic diseases. However, curcumin, a highly pleiotropic molecule with an excellent safety profile targeting multiple diseases with strong evidence on the molecular level, could not achieve its optimum therapeutic outcome in past clinical trials, largely due to its low solubility and poor bioavailability. Curcumin can be developed as a therapeutic drug through improvement in formulation properties or delivery systems, enabling its enhanced absorption and cellular uptake. This review mainly focuses on the anti-inflammatory potential of curcumin and recent developments in dosage form and nanoparticulate delivery systems with the possibilities of therapeutic application of curcumin for the prevention and/or treatment of cancer.

Topics: Animals; Anti-Inflammatory Agents; Antineoplastic Agents; Biological Availability; Chemistry, Pharmaceutical; Curcuma; Curcumin; Drug Delivery Systems; Humans; Inflammation; Molecular Targeted Therapy; Neoplasms; Phytotherapy; Plant Extracts; Signal Transduction

Several nutritional compounds are the focus of public attention because of their potential beneficial health effects. Turmeric is a spice that comes from the root Curcuma longa. Extensive research over the past half century and especially in recent years has revealed important functions of curcumin and a timely review of clinical state-of-the-art using curcumin.. In-vitro and in-vivo research has shown various activities, such as anti-inflammatory, antiviral, antifungal, cytokines release, antioxidant, immunomodulatory, enhancing of the apoptotic process, and antiangiogenic properties. Curcumin also have been shown to be a mediator of chemo-resistance and radio-resistance.. Various in-vitro and in-vivo and scarce number of clinical studies on curcumin were identified. The various effects and properties of curcumin are summarized in this review, including preclinical and especially clinical studies. This review concentrates on recent knowledge and research with curcumin clinical applications, and clinical studies, focusing on studies published between 2008 and 2011 demonstrating the gap between preclinical and clinical research.

Topics: Angiogenesis Inhibitors; Animals; Anti-Inflammatory Agents; Antifungal Agents; Antineoplastic Agents; Antioxidants; Apoptosis; Clinical Trials as Topic; Curcuma; Curcumin; Drug Evaluation, Preclinical; Functional Food; Humans; Inflammation; Models, Animal; Neoplasms; Plant Extracts; Plant Roots; Spices

Curcumin (diferuloylmethane) is the principal biochemical component of the spice turmeric and has been shown to possess potent anti-catabolic, anti-inflammatory and antioxidant, properties. This article aims to provide a summary of the actions of curcumin on articular chondrocytes from the available literature with the use of a text-mining tool. We highlight both the potential benefits and drawbacks of using this chemopreventive agent for treating osteoarthritis (OA). We also explore the recent literature on the molecular mechanisms of curcumin mediated alterations in gene expression mediated via activator protein 1 (AP-1)/nuclear factor-kappa B (NF-kappaB) signalling in chondrocytes, osteoblasts and synovial fibroblasts.. A computer-aided search of the PubMed/Medline database aided by a text-mining tool to interrogate the ResNet Mammalian database 6.0.. Recent work has shown that curcumin protects human chondrocytes from the catabolic actions of interleukin-1 beta (IL-1beta) including matrix metalloproteinase (MMP)-3 up-regulation, inhibition of collagen type II and down-regulation of beta1-integrin expression. Curcumin blocks IL-1beta-induced proteoglycan degradation, AP-1/NF-kappaB signalling, chondrocyte apoptosis and activation of caspase-3.. The available data from published in vitro and in vivo studies suggest that curcumin may be a beneficial complementary treatment for OA in humans and companion animals. Nevertheless, before initiating extensive clinical trials, more basic research is required to improve its solubility, absorption and bioavailability and gain additional information about its safety and efficacy in different species. Once these obstacles have been overcome, curcumin and structurally related biochemicals may become safer and more suitable nutraceutical alternatives to the non-steroidal anti-inflammatory drugs that are currently used for the treatment of OA.

Topics: Apoptosis; Cartilage, Articular; Caspase 3; CD18 Antigens; Cells, Cultured; Chondrocytes; Collagen Type II; Curcumin; Enzyme Inhibitors; Humans; Inflammation; Interleukin-1beta; Matrix Metalloproteinase 3; NF-kappa B; Osteoarthritis; Signal Transduction; Transcription Factor AP-1

Extensive research within the past two decades has revealed that obesity, a major risk factor for type 2 diabetes, atherosclerosis, cancer, and other chronic diseases, is a proinflammatory disease. Several spices have been shown to exhibit activity against obesity through antioxidant and anti-inflammatory mechanisms. Among them, curcumin, a yellow pigment derived from the spice turmeric (an essential component of curry powder), has been investigated most extensively as a treatment for obesity and obesity-related metabolic diseases. Curcumin directly interacts with adipocytes, pancreatic cells, hepatic stellate cells, macrophages, and muscle cells. There, it suppresses the proinflammatory transcription factors nuclear factor-kappa B, signal transducer and activators of transcription-3, and Wnt/beta-catenin, and it activates peroxisome proliferator-activated receptor-gamma and Nrf2 cell-signaling pathways, thus leading to the downregulation of adipokines, including tumor necrosis factor, interleukin-6, resistin, leptin, and monocyte chemotactic protein-1, and the upregulation of adiponectin and other gene products. These curcumin-induced alterations reverse insulin resistance, hyperglycemia, hyperlipidemia, and other symptoms linked to obesity. Other structurally homologous nutraceuticals, derived from red chili, cinnamon, cloves, black pepper, and ginger, also exhibit effects against obesity and insulin resistance.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Curcumin; Dietary Supplements; Humans; Inflammation; Insulin Resistance; Metabolic Syndrome; Obesity

Increased intestinal permeability is a likely cause of various pathologies, such as allergies and metabolic or even cardiovascular disturbances. Intestinal permeability is found in many severe clinical situations and in common disorders such as irritable bowel syndrome. In these conditions, substances that are normally unable to cross the epithelial barrier gain access to the systemic circulation. To illustrate the potential harmfulness of leaky gut, we present an argument based on examples linked to protein or lipid glycation induced by modern food processing. Increased intestinal permeability should be largely improved by dietary addition of compounds, such as glutamine or curcumin, which both have the mechanistic potential to inhibit the inflammation and oxidative stress linked to tight junction opening. This brief review aims to increase physician awareness of this common, albeit largely unrecognized, pathology, which may be easily prevented or improved by means of simple nutritional changes.

Topics: Curcumin; Diet; Dietary Supplements; Food Handling; Food Hypersensitivity; Gastrointestinal Motility; Glutamine; Glycation End Products, Advanced; Humans; Inflammation; Intestinal Absorption; Metabolic Syndrome; Permeability

The incidence of obesity is increasing worldwide and is hence considered a major public health concern. Obesity underlies the development of several metabolic complications including cardiovascular diseases, diabetes, and inflammation. Research on ways to slow the development of obesity have traditionally focused on dietary and lifestyle modifications such as restricting caloric intake and increasing physical activity. An area that has recently aroused considerable research interest is investigating the potential role of spices, particularly the Asian spice turmeric, for combating obesity. Curcumin is the active ingredient in turmeric. Evidence suggests curcumin may regulate lipid metabolism, which plays a central role in the development of obesity and its complications. The present review addresses the evidence and mechanisms by which curcumin may play a role in downregulating obesity and reducing the impact of associated problems.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Antioxidants; Curcumin; Down-Regulation; Evidence-Based Medicine; Humans; Inflammation; Lipid Metabolism; Obesity

Although safe in most cases, ancient treatments are ignored because neither their active component nor their molecular targets are well defined. This is not the case, however, with curcumin, a yellow-pigment substance and component of turmeric (Curcuma longa), which was identified more than a century ago. For centuries it has been known that turmeric exhibits anti-inflammatory activity, but extensive research performed within the past two decades has shown that this activity of turmeric is due to curcumin (diferuloylmethane). This agent has been shown to regulate numerous transcription factors, cytokines, protein kinases, adhesion molecules, redox status and enzymes that have been linked to inflammation. The process of inflammation has been shown to play a major role in most chronic illnesses, including neurodegenerative, cardiovascular, pulmonary, metabolic, autoimmune and neoplastic diseases. In the current review, we provide evidence for the potential role of curcumin in the prevention and treatment of various proinflammatory chronic diseases. These features, combined with the pharmacological safety and negligible cost, render curcumin an attractive agent to explore further.

Topics: Animals; Anti-Inflammatory Agents; Antineoplastic Agents; Autoimmune Diseases; Cardiovascular Diseases; Curcuma; Curcumin; Cytokines; Humans; Inflammation; Lung Diseases; Metabolic Diseases; Neoplasms; Neurodegenerative Diseases; Plant Extracts

Curcumin (diferuloylmethane), a yellow pigment in the spice turmeric (also called curry powder), has been used for centuries as a treatment for inflammatory diseases. Extensive research within the past two decades has shown that curcumin mediates its anti-inflammatory effects through the downregulation of inflammatory transcription factors (such as nuclear factor kappaB), enzymes (such as cyclooxygenase 2 and 5 lipoxygenase) and cytokines (such as tumor necrosis factor, interleukin 1 and interleukin 6). Because of the crucial role of inflammation in most chronic diseases, the potential of curcumin has been examined in neoplastic, neurological, cardiovascular, pulmonary and metabolic diseases. The pharmacodynamics and pharmacokinetics of curcumin have been examined in animals and in humans. Various pharmacological aspects of curcumin in vitro and in vivo are discussed in detail here.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Antioxidants; Chronic Disease; Curcuma; Curcumin; Drug Delivery Systems; Humans; Inflammation; Phytotherapy; Spices

It is largely accepted the important role of food and feeding habits on health maintenance and development of non transmissible chronic diseases (NTCD). Epidemiologic evidences show that increasing vegetable consumption positively impacts health. On the other hand, in vivo and in vitro studies in animals show that non-nutrient bioactive food substances partly explain the role of food on the maintenance of health and on the risk reduction of these diseases. The modulation of gene expression of proteins that are involved in the cellular signaling pathways of NTCD is an important mechanism of the bioactive food substances, indicating their importance in disease prevention. Bioavailability, metabolic routes and the action of the resultant metabolites of bioactive food compounds are important aspects that may affect NTCD. All these aspects have actively been investigated in the last years and resulted in a greater understanding of the beginning, progression and prevention of NTCD. This review aimed at discussing the involved mechanisms of the inflammatory response induced by obesity and the role of bioactive food compounds in modulating such response.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Antioxidants; Biological Availability; Curcumin; Diet; Food Analysis; Humans; Inflammation; Inflammation Mediators; Nutritional Physiological Phenomena; Obesity; Phenols

Curcuma longa (turmeric) has a long history of use in Ayurvedic medicine as a treatment for inflammatory conditions. Turmeric constituents include the three curcuminoids: curcumin (diferuloylmethane; the primary constituent and the one responsible for its vibrant yellow color), demethoxycurcumin, and bisdemethoxycurcumin, as well as volatile oils (tumerone, atlantone, and zingiberone), sugars, proteins, and resins. While numerous pharmacological activities, including antioxidant and antimicrobial properties, have been attributed to curcumin, this article focuses on curcumin's anti-inflammatory properties and its use for inflammatory conditions. Curcumin's effect on cancer (from an anti-inflammatory perspective) will also be discussed; however, an exhaustive review of its many anticancer mechanisms is outside the scope of this article. Research has shown curcumin to be a highly pleiotropic molecule capable of interacting with numerous molecular targets involved in inflammation. Based on early cell culture and animal research, clinical trials indicate curcumin may have potential as a therapeutic agent in diseases such as inflammatory bowel disease, pancreatitis, arthritis, and chronic anterior uveitis, as well as certain types of cancer. Because of curcumin's rapid plasma clearance and conjugation, its therapeutic usefulness has been somewhat limited, leading researchers to investigate the benefits of complexing curcumin with other substances to increase systemic bioavailability. Numerous in-progress clinical trials should provide an even deeper understanding of the mechanisms and therapeutic potential of curcumin.

Topics: Animals; Anti-Inflammatory Agents; Antineoplastic Agents; Autoimmune Diseases; Cardiovascular Diseases; Clinical Trials as Topic; Curcuma; Humans; Inflammation; Metabolic Diseases; Neoplasms; Neurodegenerative Diseases; Plant Extracts

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Chromatin Assembly and Disassembly; Curcumin; Diet; Flavonoids; Inflammation; Oxidative Stress; Phenols; Polyphenols; Resveratrol; Stilbenes

Signaling through nuclear factor-kappa B (NF-kappaB) is emerging as an important regulator of muscle development, maintenance, and regeneration. Classic signaling modulates early muscle development by enhancing proliferation and inhibiting differentiation, and alternative signaling promotes myofiber maintenance and metabolism. Likewise, NF-kappaB signaling is critical for the development of immunity. Although these processes occur normally, dysregulation of NF-kappaB signaling has prohibitive effects on muscle growth and regeneration and can perpetuate inflammation in muscle diseases. Aberrant NF-kappaB signaling from immune and muscle cells has been detected and implicated in the pathologic progression of numerous dystrophies and myopathies, indicating that targeted NF-kappaB inhibitors may prove clinically beneficial.

Topics: Animals; Curcumin; Dystrophin; Glucocorticoids; Humans; I-kappa B Kinase; Inflammation; Mice; Mice, Inbred mdx; Muscle Development; Muscular Diseases; Muscular Dystrophies; NF-kappa B; Rats; Signal Transduction; Transcriptional Activation

The expression of NF-kappaB (NF-kappaB)-dependent pro-inflammatory genes in response to oxidative stress is regulated by the acetylation-deacetylation status of histones bound to the DNA. It has been suggested that in severe asthma and in chronic obstructive pulmonary disease (COPD) patients, oxidative stress not only activates the NF-kappaB pathway but also alters the histone acetylation and deacetylation balance via post-translational modification of histone deacetylases (HDACs). Corticosteroids have been one of the major modes of therapy against various chronic respiratory diseases such as asthma and COPD. Failure of corticosteroids to ameliorate such disease conditions has been attributed to their inability to either recruit HDAC2 or to the presence of an oxidatively modified HDAC2 in asthmatics and COPD subjects. Naturally occurring polyphenols such as curcumin and resveratrol have been increasingly considered as safer nutraceuticals. Curcumin is a polyphenol present in the spice turmeric, which can directly scavenge free radicals such as superoxide anion and nitric oxide and modulate important signaling pathways mediated via NF-kappaB and mitogen-activated protein kinase pathways. Polyphenols also down-regulate expression of pro-inflammatory mediators, matrix metalloproteinases, adhesion molecules, and growth factor receptor genes and they up-regulate HDAC2 in the lung. Thus, curcumin may be a potential antioxidant and anti-inflammatory therapeutic agent against chronic inflammatory lung diseases.

Topics: Anti-Inflammatory Agents; Antioxidants; Asthma; Curcumin; Gene Expression; Glucocorticoids; Humans; Inflammation; NF-kappa B; Pulmonary Disease, Chronic Obstructive; Signal Transduction; Steroids

Curcumin (diferuloylmethane) is an orange-yellow component of turmeric (Curcuma longa), a spice often found in curry powder. In recent years, considerable interest has been focused on curcumin due to its use to treat a wide variety of disorders without any side effects. It is one of the major curcuminoids of turmeric, which impart its characteristic yellow colour. It was used in ancient times on the Indian subcontinent to treat various illnesses such as rheumatism, body ache, skin diseases, intestinal worms, diarrhoea, intermittent fevers, hepatic disorders, biliousness, urinary discharges, dyspepsia, inflammations, constipation, leukoderma, amenorrhea, and colic. Curcumin has the potential to treat a wide variety of inflammatory diseases including cancer, diabetes, cardiovascular diseases, arthritis, Alzheimer's disease, psoriasis, etc, through modulation of numerous molecular targets. This article reviews the use of curcumin for the chemoprevention and treatment of various diseases.

Topics: Antioxidants; Curcumin; Diabetes Mellitus; Humans; Inflammation; Liver Diseases; Neoplasms

Turmeric, the bright yellow spice extracted from the tuberous rhizome of the plant Curcuma longa, has been used in traditional Indian and Chinese systems of medicine for centuries to treat a variety of ailments, including jaundice and hepatic disorders, rheumatism, anorexia, diabetic wounds, and menstrual difficulties. Most of the medicinal effects of turmeric have been attributed to curcumin, the principal curcumanoid found in turmeric. Recent evidence that curcumin exhibits strong anti-inflammatory and antioxidant activities and modulates the expression of transcription factors, cell cycle proteins, and signal transducing kinases has prompted the mechanism-based studies on the potential of curcumin to primarily prevent and treat cancer and inflammatory diseases. Little work has been done to study the effect of curcumin on the development of immune responses. This review discusses current knowledge on the immunomodulatory effects of curcumin on various facets of the immune response, including its effect on lymphoid cell populations, antigen presentation, humoral and cell-mediated immunity, and cytokine production.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Antibody Formation; Antigen-Presenting Cells; Apoptosis; Curcumin; Cytokines; Cytotoxicity, Immunologic; Humans; Immune System; Immunity, Cellular; Inflammation; NF-kappa B; T-Lymphocytes

Biological, biochemical and physical stimuli activate inflammatory leukocytes, such as macrophages, resulting in induction and synthesis of proinflammatory proteins and enzymes, together with free radicals, as innate immune responses. On the other hand, chronic and dysregulated activation of some inducible enzymes, including NADPH oxidase (NOX), inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2, have been shown to play pivotal roles in the development of certain inflammatory diseases such as oncogenesis. While the use of synthetic agents, especially those targeting molecules, is an attractive and reasonable approach to prevent carcinogenesis, it should be noted that traditional herbs and spices also exist along with their active constituents, which have been demonstrated to disrupt inflammatory signal transduction pathways. In this mini-review, the molecular mechanisms of activation or induction of NOX, iNOS and COX-2, as well as some food phytochemicals with marked potential to regulate those key inflammatory molecules, are highlighted. For example, 1'-acetoxychavicol acetate, which occurs in the rhizomes of the subtropical Zingiberaceae plant, has been shown to attenuate NOX-derived superoxide generation in macrophages, as well as lipopolysaccharide-induced nitric oxide and prostaglandin E(2) production through the suppression of iNOS and COX-2 synthesis, respectively. Notably, this phytochemical has exhibited a wide range of cancer prevention activities in several rodent models of inflammation-associated carcinogenesis. Herein, the cancer preventive potentials of several food phytochemicals targeting the induction of NOX, iNOS and COX-2 are described.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Anticarcinogenic Agents; Benzyl Alcohols; Curcumin; Cyclooxygenase 2; Dinoprostone; Enzyme Induction; Enzyme Inhibitors; Food; Humans; Inflammation; Lipopolysaccharides; NADPH Oxidases; Nitric Oxide Synthase Type II; Plant Extracts; Sesquiterpenes; Terpenes

Diabetes is one of the most common chronic diseases worldwide. Systemic inflammation (high-sensitivity C-reactive protein (hs-CRP)) and lipid metabolism disruption (lipoprotein A, LipoPr (a)) play a critical role in developing and progressing atherosclerosis and acute coronary syndrome in diabetic patients. The anti-oxidant and anti-inflammatory effects of curcumin have been emphasized previously. Therefore, we aimed to evaluate the impact of nano-curcumin on cardiovascular risk factors in type 2 diabetic patients with mild to moderate coronary artery disease (CAD). We performed a randomized, double-blinded, placebo-controlled clinical trial with type 2 diabetic patients (n = 64), and mild to moderate CAD (<70% stenosis in angiography). The patients received nano-curcumin (80 mg/day) or placebo along with optimal medications for 90 days. The biofactors, including hs-CRP and LipoPr (a), and lipid profile, were measured at the admission of patients and end of the study. Nano-curcumin significantly mitigated the hs-CRP and LipoPr (a) levels following 90 days of treatment (P < 0.001 and P = 0.043, respectively). In addition, the mean percentage of change (%Δ) in the hs-CRP and LipoPr (a) levels were meaningfully reduced in the nano-curcumin group compared to the placebo group (P < 0.001 and P = 0.007, respectively). Surprisingly, nano-curcumin notably propagated the number of patients with mild (34.35%) and moderate (62.5%) hs-CRP level category and strikingly diminished the number of patients with severe hs-CRP level category (3.125%) compared to the placebo group (P = 0.016). Nano-curcumin (80 mg/day) might prevent atherosclerosis progression and, in terms of attenuating hs-CRP levels as an inflammation index, succedent cardiovascular events in diabetic heart patients.

Topics: Atherosclerosis; Biomarkers; C-Reactive Protein; Coronary Artery Disease; Curcumin; Diabetes Mellitus, Type 2; Humans; Inflammation; Lipoprotein(a)

Natural dietary compounds that can modulate the inflammation process have the potential to improve physical function through a number of biological pathways, and thus may represent an alternative approach to avert functional decline compared to more time-burdening lifestyle interventions. In this pilot trial, we tested the feasibility and explored the effect of a nutritional compound, Curcumin C3 Complex® for improving physical function and muscle strength in moderately functioning older adults with low-grade inflammation.. Moderately functioning (short physical performance battery, SPPB <10) and sedentary older adults (>65 years) with low-grade systemic inflammation (c-reactive protein >1mg/dL) were randomized to receive Curcumin C3 Complex® (n=9) (1000mg/day) or placebo (n=8) groups for 12 weeks. All participants (age range: 66-94 years, 8 females and 9 males) underwent functional testing (SPPB and walking speed by the 400-meter walk test) and lower-limb strength (knee flexion and extension peak torque by the Biodex test) at baseline and 12 weeks. Venous blood was collected at baseline, 4, 8 and 12 weeks for safety blood chemistry analyses and biomarkers of inflammation.. A total of 17 participants were randomized and completed the study. Adherence was high (> 90%) and there were no adverse events reported or abnormal blood chemistries reported. Based on effect sizes, participants in the Curcumin C3 Complex® group demonstrated large effect sizes in the SPPB (Cohen's effect size d=0.75) and measures of knee extension (d=0.69) and flexion peak torque (d=0.82). Effect sizes for galectin-3 (d=-0.31) (larger decrease) and interleukin-6 (d=0.38) (smaller increase) were small in the Curcumin C3 Complex® group compared to placebo.. This pilot trial suggests that there were no difficulties with recruitment, adherence and safety specific to the study protocol. Preliminary findings warrant a Phase IIb clinical trial to test the effect of Curcumin C3 Complex® on physical function and muscle strength in older adults at risk for mobility disability.

Topics: Aged; Aged, 80 and over; Curcumin; Diet; Female; Humans; Inflammation; Male; Muscle Strength; Pilot Projects

Premenstrual syndrome (PMS) and primary dysmenorrhea are common gynecological problems and inflammation may have a role in their etiology. Curcumin is a polyphenolic natural product for which there is increasing evidence of anti-inflammatory and iron chelation effects. This study assessed the effects of curcumin on inflammatory biomarkers and iron profile in young women with PMS and dysmenorrhea. A sample of 76 patients was included in this triple-blind, placebo-controlled clinical trial. Participants were randomly allocated to curcumin (n = 38) and control groups (n = 38). Each participant received one capsule (500 mg of curcuminoid+ piperine, or placebo) daily, from 7 days before until 3 days after menstruation for three consecutive menstrual cycles. Serum iron, ferritin, total iron-binding capacity (TIBC) and high-sensitivity C-reactive protein (hsCRP), as well as white blood cell, lymphocyte, neutrophil, platelet counts, mean platelet volume (MPV) and red blood cell distribution width (RDW), were quantified. Neutrophil: lymphocyte ratio (NLR), platelet: lymphocyte ratio (PLR), and RDW: platelet ratio (RPR) were also calculated. Curcumin significantly decreased the median (interquartile range) serum levels of hsCRP [from 0.30 mg/L (0.0-1.10) to 0.20 mg/L (0.0-1.3); p = 0.041] compared with placebo, but did not show any difference for neutrophil, RDW, MPV, NLR, PLR and RPR values (p > 0.05). The treatment schedule was well-tolerated, and none of markers of iron metabolism statistically changed after the intervention in the curcumin group (p > 0.05). Curcumin supplementation may have positive effects on serum hsCRP, a marker of inflammation, with no any changes on iron homeostasis in healthy women with PMS and dysmenorrhea.

Topics: Biomarkers; C-Reactive Protein; Curcumin; Dysmenorrhea; Female; Humans; Inflammation; Iron; Lymphocytes; Neutrophils; Premenstrual Syndrome

Colorectal cancer prevention is crucial for public health, given its high mortality rates, particularly in young adults. The early detection and treatment of precancerous lesions is key to preventing carcinogenesis progression. Natural compounds like curcumin and anthocyanins show promise in impeding adenomatous polyp progression in preclinical models. We conducted a randomized, double-blind, placebo-controlled, phase II presurgical trial in 35 patients with adenomatous polyps to explore the biological effects of curcumin and anthocyanins on circulating biomarkers of inflammation and metabolism. No significant difference in biomarker changes by treatment arm was observed. However, the network analysis before treatment revealed inverse correlations between adiponectin and BMI and glycemia, as well as direct links between inflammatory biomarkers and leptin and BMI. In addition, a considerable inverse relationship between adiponectin and grade of dysplasia was detected after treatment (corr = -0.45). Finally, a significant increase in IL-6 at the end of treatment in subjects with high-grade dysplasia was also observed (

Topics: Adenoma; Adiponectin; Anthocyanins; Biomarkers; Carcinogenesis; Colorectal Neoplasms; Curcumin; Humans; Hyperplasia; Inflammation; Young Adult

Topics: Adult; Blood Glucose; Cholesterol; Curcuma; Double-Blind Method; Humans; Hypertension; Inflammation; Insulin Resistance; Metabolic Syndrome; Obesity; Obesity, Abdominal

Chronic kidney disease (CKD) subjects suffer from high risk of cardiovascular mortality, and any intervention preventing the progression of CKD may have an enormous impact on public health. In the last decade, there has been growing awareness that the gut microbiota (GM) can play a pivotal role in controlling the pathogenesis of systemic inflammatory state and CKD progression. To ameliorate the quality of life in CKD subjects, the use of dietary supplements has increased over time. Among those, curcumin has demonstrated significant in vitro anti-inflammatory properties. In this pilot study, 24 CKD patients and 20 healthy volunteers were recruited. CKD patients followed nutritional counselling and were supplemented with curcumin (Meriva

Topics: Aged; Case-Control Studies; Curcumin; Dietary Supplements; Female; Gastrointestinal Microbiome; Humans; Inflammation; Lipid Peroxidation; Male; Pilot Projects; Renal Insufficiency, Chronic; Treatment Outcome; Uremic Toxins

Recent studies have shed light on the potential role of curcumin in mitigating inflammation in patients with chronic kidney disease (CKD). This study aimed to evaluate the effects of curcumin supplementation on plasma levels of markers of inflammation and oxidative stress in patients with CKD undergoing hemodialysis (HD).. These are secondary exploratory analyses from a previous double-blind, randomized controlled pilot study registered under ClinicalTrials.gov Identifier no. NCT00123456. It included 28 hemodialysis patients from a previous study divided into two groups: curcumin group (receiving juice with 2.5 g of turmeric 3×/week for 12 weeks) and a control group. The TNF-α, IL-6 and Ox-LDL plasma levels were measured by sandwich enzyme immunoassays ELISA; lipid peroxidation was measured by the reaction between malondialdehyde (MDA) and thiobarbituric acid.. After 12 weeks of supplementation with curcumin, the TNF-α plasma levels were significantly reduced [from 15.0 (8.23-73.3) to 6.17 (1.11-55.0) pg/mL, p = 0.01].. 12 weeks of treatment with curcumin in HD patients resulted in a reduction in the biomarker of inflammation (TNF-α), confirming our previous hypothesis that curcumin has an anti-inflammatory effect.

Topics: Biomarkers; Curcumin; Dietary Supplements; Double-Blind Method; Humans; Inflammation; Oxidative Stress; Renal Dialysis; Renal Insufficiency, Chronic; Tumor Necrosis Factor-alpha

Osteoarthritis (OA) is a high-incidence, chronic condition, with an extremely high prevalence among older adults. OA seriously compromises the normal living of OA patients, and it's imperative to find a novel therapy as soon as possible to improve their prognosis and life quality.. The study intended to investigate the therapeutic effects of Curcumin (Cur) on OA and to explore its preliminary mechanism of action, with the aim of offering more accurate guidance for use of OA therapy.. The research team designed a prospective non-randomized controlled trial.. The study took place in the Department of Orthopedics at Sir Run Run Hospital at Nanjing Medical University in Nanjing, China.. Participants were 107 OA patients treated at the hospital between March 2019 and January 2020.. Participants were divided into two groups, 51 in the Cur group and 56 in the ibuprofen group.. The clinical efficacy and safety of the two groups were observed. In addition, the research team performed in-vitro studies. Chondrocytes HC-a and C28/I2 were purchased to evaluate the intracellular inflammatory response and apoptosis rate under the intervention of Cur and Wnt/β-catenin pathway inhibitors.. No significant differences existed in the clinical-efficacy rate between the two groups (P > .05), but the Cur group show higher improvements in safety, joint mobility, and inhibition of inflammation (P < .05). In-vitro experiments showed that Cur inhibited the apoptosis rate of chondrocytes and the levels of inflammatory factors, while the Wnt/β-catenin inhibitor did the opposite (P < .05).. Cur can effectively decrease the pathological results of OA, with a remarkable safety profile; its mechanism may be the activation of the Wnt/β-catenin signaling pathway to inhibit the inflammatory reaction and apoptosis in chondrocytes.

Topics: Aged; beta Catenin; Cartilage, Articular; Chondrocytes; Curcumin; Humans; Inflammation; Osteoarthritis; Prospective Studies; Wnt Signaling Pathway

Under the intensive modern poultry farming system, the lung of duck is one of the main target organs for various bacterial and viral infections. Curcumin is a kind of natural polyphenol compound for which various beneficial biological functions exist, including being an anti-inflammatory, antioxidant, and antiviral. The aim of this work was to investigate the mechanism of curcumin-alleviated lipopolysaccharide (LPS)-induced lung damage by the nuclear erythroid 2-related factor 2 (Nrf2)-antioxidant reaction element (ARE) and nuclear factor kappa B (NF-κB) signaling pathway in ducks.. In total, 450 one-day-old male specific pathogen-free ducks were randomly assigned into three dietary treatments: CON, basal diet; LPS, basal diet + LPS treatment; LPS + CUR, basal diet + LPS + 500 mg kg. In conclusion, dietary supplementation of 500 mg kg

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Antiviral Agents; Curcumin; Ducks; Inflammation; Lipopolysaccharides; Lung Injury; Male; NF-E2-Related Factor 2; NF-kappa B; Phosphates; Polyphenols; Saline Solution; Signal Transduction

Arsenic is a toxic heavy metal widely found in the natural environment and has adverse effects on the health of waterfowl and human. Curcumin (CUR), a natural pigment of the golden spice turmeric, exhibits excellent anti-tumor, anti-inflammatory and anti-oxidant activities. But the effects of CUR on duck spleen exposed to arsenic remain largely unknown. In this study, 75 ducks were divided randomly into Control, L-ATO, M-ATO, H-ATO and CUR + H-ATO groups to systematically analyze the underlying role of CUR. The results showed that arsenic trioxide (ATO) led to growth retardation of ducks, hyaline degeneration and sparse cell arrangement on their spleen. And in the ATO-exposed ducks, the levels of immunoglobulins (Ig; IgA, IgG, IgM) in the serum and the expression of autophagy-related genes (Atg5, P62, LC3I, LC3II, LC3II/I, Beclin-1) were significantly upregulated compared with the control ducks. Moreover, ATO also activated NF-κB signal pathway and upregulated the expression of pro-inflammatory cytokines (TNF-α, IFN-γ, IL-1β, IL-2, IL-18). Meanwhile, application of CUR alleviated the ATO toxicity with the release of growth inhibition, and the reduced hyaline degeneration and distortion of the spleen capsule. CUR also suppressed ATO-induced NF-κB activation, pro-inflammatory cytokine addition and expression of autophagy-related genes. Overall, these results suggested that CUR might exert a protective effect against ATO-induced immunosuppression in ducks via anti-inflammation and autophagy restoring.

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Arsenic; Arsenic Trioxide; Autophagy; Beclin-1; Curcumin; Cytokines; Ducks; Immunoglobulin A; Immunoglobulin G; Immunoglobulin M; Inflammation; Interleukin-18; Interleukin-2; Metals, Heavy; NF-kappa B; Spleen; Tumor Necrosis Factor-alpha

Preclinical models have demonstrated the anti-inflammatory and lipid-lowering effects of curcumin. Innovative formulations have been developed to overcome the poor bioavailability of native curcumin. The study hypothesizes that the bioavailability of micellar curcumin is superior to native curcumin and investigates the potential anti-inflammatory and proprotein convertase subtilisin/kexin type 9 (PCSK9) concentration lowering effects.. In this double-blind, randomized, crossover trial, 15 healthy volunteers receive micellar or native curcumin (105 mg day. Micellar curcumin demonstrates an improved oral bioavailability but does not show anti-inflammatory effects in this model. Potential effects on PCSK9 concentrations warrant further investigation.

Topics: Anti-Inflammatory Agents; Biomarkers; Cross-Over Studies; Curcumin; Healthy Volunteers; Humans; Inflammation; Interleukin-6; Micelles; Proprotein Convertase 9

Gastrointestinal dysfunction is associated with a disturbance of immune homeostasis, changes in the intestinal microbiome, alteration of the composition of the bile acid pool, and dynamic imbalance of group 3 innate lymphoid cells (ILC3s). Curcumin (CUR), a polyphenolic compound isolated from turmeric, has been known to attenuate intestinal inflammation in potential therapies for gastrointestinal diseases. It was hypothesized that CUR could target the gut microbiome to modulate bile acid (BA) metabolism and the function of ILC3s in ameliorating lipopolysaccharide (LPS)-induced imbalance of intestinal homeostasis in chickens. Seven hundred and twenty 1-day-old crossbred chickens were randomly divided into four treatments, namely CON_saline (basal diet + saline control), CUR_saline (basal diet + 300 mg kg

Topics: Animals; Bile Acids and Salts; Chickens; Curcumin; Cytokines; Gastrointestinal Microbiome; Homeostasis; Immunity, Innate; Inflammation; Lipopolysaccharides; Lymphocytes

The dietary spice Curcuma longa L. (C. longa), also known as turmeric, has various biological effects. A hot water extract of C. longa was shown to have anti-inflammatory activities in preclinical and clinical studies. Chronic low-grade inflammation is associated with the disruption of glucose homeostasis, but the effect of C. longa extract on glucose metabolism in humans is poorly understood. Therefore, we investigated the effect of C. longa extracts on serum glucose levels in the presence of low-grade inflammation. We reanalyzed our published data from two randomized, double-blind, placebo-controlled trials in overweight participants aged 50 to 69 years and performed a stratified analysis using the inflammatory marker high-sensitivity C-reactive protein (hsCRP). In both studies, participants took a test food with a hot water extract of C. longa (C. longa extract group, n = 45 per study) or without C. longa extract (placebo group, n = 45 per study) daily for 12 weeks, and we measured the levels of serum hsCRP and fasting serum glucose. The mean baseline hsCRP value was used to stratify participants into two subgroups: a low-hsCRP subgroup (baseline mean hsCRP < 0.098 mg/dL) and a high-hsCRP subgroup (baseline mean hsCRP ≥ 0.098 mg/dL). In the low-hsCRP subgroup, we found no significant difference in fasting serum glucose levels between the two groups in either study, but in the high-hsCRP subgroup, the C. longa extract group had significantly lower levels of serum hsCRP (p < 0.05) and fasting serum glucose (p < 0.05) than the placebo group in both studies. In conclusion, a hot water extract of C. longa may help to improve systemic glucose metabolism in people with chronic low-grade inflammation.

Topics: Anti-Inflammatory Agents; C-Reactive Protein; Curcuma; Double-Blind Method; Fasting; Glucose; Humans; Inflammation; Plant Extracts; Water

Turmeric has renop rotective effects that can act to reduce oxidative stress and inflammation in hemodialysis (HD) patients. Piperine has been indicated as a bioavailability enhancer of turmeric and consequently of its biological effects. However, data on the efficacy of the turmeric/piperine combination in HD patients are limited. We aimed to verify whether turmeric supplementation in combination with piperine has a superior effect to turmeric alone in increasing antioxidant capacity and reducing oxidative stress and inflammation in HD patients.. This randomized, double-blind clinical trial was conducted in HD patients (age 20-75 years). Patients were supplemented with turmeric (3 g/day) or turmeric/piperine (3 g turmeric + 2 mg piperine/day) for 12 weeks. Malondialdehyde (MDA), antioxidant enzymes catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), high-sensitivity C-reactive protein (hs-CRP), and ferritin were evaluated at baseline and the end of the study.. There was a reduction in the MDA and ferritin levels in the turmeric/piperine group and in the comparison between groups at the end of the study [MDA: -0.08(-0.14/0.01) nmol/mL versus -0.003(-0.10/0.26) nmol/mL, p = 0.003; ferritin: -193.80 ± 157.29 mg/mL versus 51.99 ± 293.25 mg/mL, p = 0.018]. In addition, GPx activity reduced in the turmeric group (p = 0.029). No changes were observed for CAT, GR, and hs-CRP.. Turmeric plus piperine was superior to turmeric alone in decreasing MDA and ferritin levels. The use of a combination of turmeric and piperine as a dietary intervention may be beneficial for modulating the status oxidative and inflammation in HD patients.. RBR-2t5zpd; Registration Date: May 2, 2018.

Topics: Antioxidants; C-Reactive Protein; Curcuma; Dietary Supplements; Double-Blind Method; Ferritins; Inflammation; Oxidative Stress; Renal Dialysis

Unprecedented community containment measures were taken following the recent outbreak of COVID-19 in Italy. The aim of the study was to explore the self-reported future compliance of citizens with such measures and its relationship with potentially impactful psychological variables.. An online survey was completed by 931 people (18-76 years) distributed across the Italian territory. In addition to demographics, five dimensions were measured: self-reported compliance with containment measures over time (today, at 7, 14, 30, 60, 90, and 180 days from now) at three hypothetical risk levels (10, 50, 90% of likelihood of contracting the COVID-19), perceived risk, generalized anxiety, intolerance of uncertainty, and relevance of several psychological needs whose satisfaction is currently precluded.. The duration of containment measures plays a crucial role in tackling the spread of the disease as people will be less compliant over time. Psychological needs of citizens impacting on the compliance should be taken into account when planning an easing of the lockdown, along with interventions for protecting vulnerable groups from mental distress.. La apendicitis aguda (AA) es la urgencia quirúrgica abdominal más frecuente. No encontramos estudios específicos que evalúen el impacto de la pandemia causada por el coronavirus 2 (SARS-Cov-2) sobre la AA y su tratamiento quirúrgico. Analizamos la influencia de esta nueva patología sobre la AA.. Estudio observacional retrospectivo en pacientes intervenidos por AA desde enero hasta abril de 2020. Fueron clasificados según el momento de la apendicectomía, antes de la declaración del estado de alarma (Pre-COVID19) y después de la declaración del estado de alarma (Post-COVID19) en España. Se evaluaron variables demográficas, duración de la sintomatología, tipo de apendicitis, tiempo quirúrgico, estancia hospitalaria y complicaciones postoperatorias.. La pandemia por SARS-Cov-2 influye en el momento de diagnóstico de la apendicitis, así como en su grado de evolución y estancia hospitalaria. La peritonitis fue lo más frecuentemente observado. Una sospecha y orientación clínica más temprana, es necesaria para evitar un manejo inadecuado de este trastorno quirúrgico común.. The primary outcome is improvement in PaO. Findings will provide timely information on the safety, efficacy, and optimal dosing of t-PA to treat moderate/severe COVID-19-induced ARDS, which can be rapidly adapted to a phase III trial (NCT04357730; FDA IND 149634).. None.. The gut barrier is crucial in cirrhosis in preventing infection-causing bacteria that normally live in the gut from accessing the liver and other organs via the bloodstream. Herein, we characterised gut inflammation by measuring different markers in stool samples from patients at different stages of cirrhosis and comparing this to healthy people. These markers, when compared with equivalent markers usually measured in blood, were found to be very different in pattern and absolute levels, suggesting that there is significant gut inflammation in cirrhosis related to different immune system pathways to that seen outside of the gut. This provides new insights into gut-specific immune disturbances that predispose to complications of cirrhosis, and emphasises that a better understanding of the gut-liver axis is necessary to develop better targeted therapies.. La surveillance de l’intervalle QT a suscité beaucoup d’intérêt durant la pandémie de la COVID-19 en raison de l’utilisation de médicaments prolongeant l’intervalle QT et les préoccupations quant à la transmission virale par les électrocardiogrammes (ECG) en série. Nous avons posé l’hypothèse que la surveillance en continu de l’intervalle QT par télémétrie était associée à une meilleure détection des épisodes de prolongation de l’intervalle QT.. Nous avons introduit la télémétrie cardiaque en continu (TCC) à l’aide d’un algorithme de surveillance automatisée de l’intervalle QT dans nos unités de COVID-19. Les mesures automatisées quotidiennes de l’intervalle QT corrigé (auto-QTc) en fonction de la fréquence cardiaque maximale ont été enregistrées. Nous avons comparé la proportion des épisodes de prolongation marquée de l’intervalle QTc (QTc long), définie par un intervalle QTc ≥ 500 ms, chez les patients montrant une suspicion de COVID-19 ou ayant la COVID-19 qui avaient été admis avant et après la mise en place de la TCC (groupe témoin. La surveillance en continu de l’intervalle QT est supérieure à la norme de soins dans la détection des épisodes de QTc long et exige peu d’ECG. La réponse clinique aux épisodes de QTc long est sous-optimale.. Exposure to a model wildfire air pollution source modifies cardiovascular responses to HC challenge, suggesting air pollution sensitizes the body to systemic triggers.. Though the majority of HIV-infected adults who were on HAART had shown viral suppression, the rate of suppression was sub-optimal according to the UNAIDS 90-90-90 target to help end the AIDS pandemic by 2020. Nonetheless, the rate of immunological recovery in the study cohort was low. Hence, early initiation of HAART should be strengthened to achieve good virological suppression and immunological recovery.. Dust in Egyptian laying hen houses contains high concentrations of microorganisms and endotoxins, which might impair the health of birds and farmers when inhaled. Furthermore, laying hens in Egypt seem to be a reservoir for ESBL-producing Enterobacteriaceae. Thus, farmers are at risk of exposure to ESBL-producing bacteria, and colonized hens might transmit these bacteria into the food chain.. The lack of significant differences in the absolute changes and relative ratios of injury and repair biomarkers by contrast-associated AKI status suggests that the majority of mild contrast-associated AKI cases may be driven by hemodynamic changes at the kidney.. Most comparisons for different outcomes are based on very few studies, mostly low-powered, with an overall low CoE. Thus, the available evidence is considered insufficient to either support or refute CH effectiveness or to recommend one ICM over another. Therefore, further well-designed, larger RCTs are required.. PROSPERO database Identifier: CRD42016041953.. Untouched root canal at cross-section perimeter, the Hero 642 system showed 41.44% ± 5.62% and Reciproc R40 58.67% ± 12.39% without contact with instruments. Regarding the untouched area, Hero 642 system showed 22.78% ± 6.42% and Reciproc R40 34.35% ± 8.52%. Neither instrument achieved complete cross-sectional root canal debridement. Hero 642 system rotary taper 0.02 instruments achieved significant greater wall contact perimeter and area compared to reciprocate the Reciproc R40 taper 0.06 instrument.. Hero 642 achieved higher wall contact perimeter and area but, regardless of instrument size and taper, vital pulp during. The functional properties of the main mechanisms involved in the control of muscle Ca. This study showed that the anti-inflammatory effect of the iron-responsive product DHA in arthritis can be monitored by an iron-like radioactive tracer (. Attenuated vascular reactivity during pregnancy suggests that the systemic vasodilatory state partially depletes nitric oxide bioavailability. Preliminary data support the potential for MRI to identify vascular dysfunction in vivo that underlies PE. Level of Evidence 2 Technical Efficacy Stage 1 J. MAGN. RESON. IMAGING 2021;53:447-455.. La evaluación de riesgo es importante para predecir los resultados postoperatorios en pacientes con cáncer gastroesofágico. Este estudio de cohortes tuvo como objetivo evaluar los cambios en la composición corporal durante la quimioterapia neoadyuvante e investigar su asociación con complicaciones postoperatorias. MÉTODOS: Los pacientes consecutivos con cáncer gastroesofágico sometidos a quimioterapia neoadyuvante y cirugía con intención curativa entre 2016 y 2019, identificados a partir de una base de datos específica, se incluyeron en el estudio. Se utilizaron las imágenes de tomografía computarizada, antes y después de la quimioterapia neoadyuvante, para evaluar el índice de masa muscular esquelética, la sarcopenia y el índice de grasa visceral y subcutánea.. In this in vitro premature infant lung model, HF oscillation of BCPAP was associated with improved CO. Our results showed that HPC significantly promotes neurogenesis after MCAO and ameliorates neuronal injury.. Inflammatory markers are highly related to signs of systemic hypoperfusion in CS. Moreover, high PCT and IL-6 levels are associated with poor prognosis.. These findings indicate that Tetrapleura tetraptera fruit has a protective potential against stroke through modulation of redox and electrolyte imbalances, and attenuation of neurotransmitter dysregulation and other neurochemical dysfunctions. Tetrapleura tetraptera fruit could be a promising source for the discovery of bioactives for stroke therapy.

Topics: 3T3-L1 Cells; A Kinase Anchor Proteins; Acetates; Achilles Tendon; Acute Kidney Injury; Acute Pain; Acyclic Monoterpenes; Adenine Nucleotides; Adhesins, Escherichia coli; Adipocytes; Adipocytes, Brown; Adipogenesis; Administration, Inhalation; Administration, Oral; Adrenal Cortex Hormones; Adsorption; Adult; Aeromonas hydrophila; Africa; Aged; Aged, 80 and over; Agrobacterium tumefaciens; Air; Air Pollutants; Air Pollution; Air Pollution, Indoor; Algorithms; Alkaloids; Alkynes; Allosteric Regulation; Amines; Amino Acid Sequence; Amino Acids; Amino Acids, Branched-Chain; Aminoisobutyric Acids; Aminopyridines; Amyotrophic Lateral Sclerosis; Anaerobic Threshold; Angiography; Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Animal Distribution; Animal Feed; Animal Nutritional Physiological Phenomena; Animals; Ankle Joint; Anti-Bacterial Agents; Anti-HIV Agents; Anti-Inflammatory Agents; Antibodies, Bacterial; Antifungal Agents; Antimalarials; Antineoplastic Agents; Antineoplastic Agents, Phytogenic; Antioxidants; Antiretroviral Therapy, Highly Active; Antiviral Agents; Aotidae; Apelin; Apoptosis; Arabidopsis Proteins; Argentina; Arginine; Artemisinins; Arthritis, Experimental; Arthritis, Rheumatoid; Arthroscopy; Aspergillus; Aspergillus niger; Asteraceae; Asthma; ATP Binding Cassette Transporter, Subfamily B, Member 1; ATP Binding Cassette Transporter, Subfamily G, Member 2; Auditory Cortex; Autoantibodies; Autophagy; Bacteria; Bacterial Infections; Bacterial Proteins; Bacterial Typing Techniques; Base Composition; Base Sequence; Basketball; Beclin-1; Benzhydryl Compounds; Benzimidazoles; Benzo(a)pyrene; Benzofurans; Benzoxazines; Bereavement; beta Catenin; beta-Lactamase Inhibitors; beta-Lactamases; beta-Lactams; Betacoronavirus; Betaine; Binding Sites; Biofilms; Biological Assay; Biological Availability; Biological Evolution; Biomarkers; Biomechanical Phenomena; Biopolymers; Biopsy; Bismuth; Blood Glucose; Blood Platelets; Blood Pressure; Body Composition; Body Weight; Bone Marrow; Bone Marrow Cells; Bone Regeneration; Boron; Botrytis; Brain Ischemia; Brain Neoplasms; Brain-Derived Neurotrophic Factor; Brazil; Breast Neoplasms; Breath Tests; Bronchoalveolar Lavage Fluid; Burkholderia; C-Reactive Protein; Caenorhabditis elegans; Caenorhabditis elegans Proteins; Calcification, Physiologic; Calcium; Calcium Signaling; Calorimetry, Differential Scanning; Cameroon; Camptothecin; Candida; Candida albicans; Capillaries; Carbapenem-Resistant Enterobacteriaceae; Carbapenems; Carbohydrate Conformation; Carbon; Carbon Dioxide; Carbon Isotopes; Carcinoma, Ovarian Epithelial; Cardiac Output; Cardiomyopathy, Hypertrophic; Cardiotonic Agents; Cardiovascular Diseases; Caregivers; Carps; Case-Control Studies; Catalase; Catalysis; Cats; CD4 Lymphocyte Count; Cell Culture Techniques; Cell Differentiation; Cell Line, Tumor; Cell Membrane; Cell Movement; Cell Proliferation; Cell Survival; Cells, Cultured; Cellulose; Centrosome; Ceratopogonidae; Chickens; Child; China; Cholera Toxin; Choline; Cholinesterases; Chromatography, High Pressure Liquid; Chromatography, Liquid; Chromatography, Micellar Electrokinetic Capillary; Chromatography, Reverse-Phase; Chronic Disease; Cinnamates; Cities; Citrates; Climate Change; Clinical Trials, Phase III as Topic; Coal; Coal Mining; Cohort Studies; Coinfection; Colchicine; Colony Count, Microbial; Colorectal Neoplasms; Coloring Agents; Common Cold; Complement Factor H; Computational Biology; Computer Simulation; Continuous Positive Airway Pressure; Contrast Media; Coordination Complexes; Coronary Artery Bypass; Coronavirus 3C Proteases; Coronavirus Infections; Coronavirus Protease Inhibitors; Corynebacterium glutamicum; Cosmetics; COVID-19; Creatinine; Cross-Sectional Studies; Crotonates; Crystallography, X-Ray; Cues; Culicidae; Culture Media; Curcuma; Cyclopentanes; Cyclopropanes; Cymbopogon; Cystine; Cytochrome P-450 CYP2B6; Cytochrome P-450 CYP2C19; Cytochrome P-450 CYP2C19 Inhibitors; Cytokines; Databases, Genetic; Death; Dendritic Cells; Density Functional Theory; Depsides; Diabetes Mellitus, Type 2; Diamond; Diarylheptanoids; Dibenzofurans; Dibenzofurans, Polychlorinated; Diclofenac; Diet; Dietary Carbohydrates; Dietary Supplements; Diffusion Magnetic Resonance Imaging; Dioxins; Diphenylamine; Disease Outbreaks; Disease Susceptibility; Disulfides; Dithiothreitol; Dizocilpine Maleate; DNA Methylation; DNA-Binding Proteins; DNA, Bacterial; Dogs; Dose-Response Relationship, Drug; Double-Blind Method; Doublecortin Protein; Drosophila melanogaster; Droughts; Drug Carriers; Drug Combinations; Drug Delivery Systems; Drug Liberation; Drug Resistance; Drug Resistance, Bacterial; Drug Resistance, Neoplasm; Drug Screening Assays, Antitumor; Dust; Dynactin Complex; Dysferlin; Echo-Planar Imaging; Echocardiography; Edaravone; Egypt; Elasticity; Electrodes; Electrolytes; Emodin; Emtricitabine; Endometriosis; Endothelium, Vascular; Endotoxins; Energy Metabolism; Energy Transfer; Enterobacteriaceae; Enterococcus faecalis; Enterotoxigenic Escherichia coli; Environmental Monitoring; Enzyme Inhibitors; Epidemiologic Factors; Epigenesis, Genetic; Erythrocytes; Escherichia coli; Escherichia coli Infections; Escherichia coli Vaccines; Esophageal Neoplasms; Esophagectomy; Esophagogastric Junction; Esterases; Esterification; Ethanol; Ethiopia; Ethnicity; Eucalyptus; Evidence-Based Practice; Exercise; Exercise Tolerance; Extracorporeal Membrane Oxygenation; Family; Fatty Acids; Feedback; Female; Ferric Compounds; Fibrin Fibrinogen Degradation Products; Filtration; Fish Diseases; Flavonoids; Flavonols; Fluorodeoxyglucose F18; Follow-Up Studies; Food Microbiology; Food Preservation; Forests; Fossils; Free Radical Scavengers; Freund's Adjuvant; Fruit; Fungi; Gallium; Gender Identity; Gene Expression Regulation; Gene Expression Regulation, Neoplastic; Gene Expression Regulation, Plant; Gene Knockdown Techniques; Genes, Bacterial; Genes, Plant; Genetic Predisposition to Disease; Genitalia; Genotype; Glomerulonephritis, IGA; Glottis; Glucocorticoids; Glucose; Glucuronides; Glutathione Transferase; Glycogen Synthase Kinase 3 beta; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Grassland; Guinea Pigs; Half-Life; Head Kidney; Heart Atria; Heart Rate; Heart Septum; HEK293 Cells; Hematopoietic Stem Cells; Hemodynamics; Hep G2 Cells; Hepacivirus; Hepatitis C; Hepatitis C, Chronic; Hepatocytes; Hesperidin; High-Frequency Ventilation; High-Temperature Requirement A Serine Peptidase 1; Hippocampus; Hirudins; History, 20th Century; History, 21st Century; HIV Infections; Homeostasis; Hominidae; Housing, Animal; Humans; Hydrocarbons, Brominated; Hydrogen Bonding; Hydrogen Peroxide; Hydrogen-Ion Concentration; Hydroxybutyrates; Hydroxyl Radical; Hypertension; Hypothyroidism; Image Interpretation, Computer-Assisted; Immunoconjugates; Immunogenic Cell Death; Indoles; Infant, Newborn; Infant, Premature; Infarction, Middle Cerebral Artery; Inflammation; Inflammation Mediators; Infrared Rays; Inhibitory Concentration 50; Injections, Intravenous; Interferon-gamma; Interleukin-23; Interleukin-4; Interleukin-6; Intermediate Filaments; Intermittent Claudication; Intestine, Small; Iridoid Glucosides; Iridoids; Iron; Isomerism; Isotope Labeling; Isoxazoles; Itraconazole; Kelch-Like ECH-Associated Protein 1; Ketoprofen; Kidney Failure, Chronic; Kinetics; Klebsiella pneumoniae; Lactams, Macrocyclic; Lactobacillus; Lactulose; Lakes; Lamivudine; Laparoscopy; Laparotomy; Laryngoscopy; Leucine; Limit of Detection; Linear Models; Lipid A; Lipopolysaccharides; Listeria monocytogenes; Liver; Liver Cirrhosis; Logistic Models; Longitudinal Studies; Losartan; Low Back Pain; Lung; Lupinus; Lupus Erythematosus, Systemic; Machine Learning; Macular Degeneration; Madin Darby Canine Kidney Cells; Magnetic Phenomena; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Magnetics; Malaria, Falciparum; Male; Mannans; MAP Kinase Signaling System; Mass Spectrometry; Melatonin; Membrane Glycoproteins; Membrane Proteins; Meniscectomy; Menisci, Tibial; Mephenytoin; Mesenchymal Stem Cells; Metal Nanoparticles; Metal-Organic Frameworks; Methionine; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Nude; Mice, Obese; Mice, Transgenic; Microbial Sensitivity Tests; Microcirculation; MicroRNAs; Microscopy, Video; Microtubules; Microvascular Density; Microwaves; Middle Aged; Minimally Invasive Surgical Procedures; Models, Animal; Models, Biological; Models, Molecular; Models, Theoretical; Molecular Docking Simulation; Molecular Structure; Molecular Weight; Morus; Mouth Floor; Multicenter Studies as Topic; Multiple Sclerosis; Multiple Sclerosis, Relapsing-Remitting; Muscle, Skeletal; Myocardial Ischemia; Myocardium; NAD; NADP; Nanocomposites; Nanoparticles; Naphthols; Nasal Lavage Fluid; Nasal Mucosa; Neisseria meningitidis; Neoadjuvant Therapy; Neoplasm Invasiveness; Neoplasm Recurrence, Local; Neoplasms, Experimental; Neural Stem Cells; Neuroblastoma; Neurofilament Proteins; Neurogenesis; Neurons; New York; NF-E2-Related Factor 2; NF-kappa B; Nicotine; Nitriles; Nitrogen; Nitrogen Fixation; North America; Observer Variation; Occupational Exposure; Ochrobactrum; Oils, Volatile; Olea; Oligosaccharides; Omeprazole; Open Field Test; Optimism; Oregon; Oryzias; Osmolar Concentration; Osteoarthritis; Osteoblasts; Osteogenesis; Ovarian Neoplasms; Ovariectomy; Oxadiazoles; Oxidation-Reduction; Oxidative Stress; Oxygen; Ozone; p38 Mitogen-Activated Protein Kinases; Pakistan; Pandemics; Particle Size; Particulate Matter; Patient-Centered Care; Pelargonium; Peptides; Perception; Peripheral Arterial Disease; Peroxides; Pets; Pharmaceutical Preparations; Pharmacogenetics; Phenobarbital; Phenols; Phenotype; Phosphates; Phosphatidylethanolamines; Phosphines; Phospholipids; Phosphorus; Phosphorylation; Photoacoustic Techniques; Photochemotherapy; Photosensitizing Agents; Phylogeny; Phytoestrogens; Pilot Projects; Plant Components, Aerial; Plant Extracts; Plant Immunity; Plant Leaves; Plant Oils; Plants, Medicinal; Plasmodium berghei; Plasmodium falciparum; Platelet Activation; Platelet Function Tests; Pneumonia, Viral; Poaceae; Pogostemon; Poloxamer; Poly I; Poly(ADP-ribose) Polymerase Inhibitors; Polychlorinated Biphenyls; Polychlorinated Dibenzodioxins; Polycyclic Compounds; Polyethylene Glycols; Polylysine; Polymorphism, Genetic; Polymorphism, Single Nucleotide; Population Dynamics; Portasystemic Shunt, Transjugular Intrahepatic; Positron Emission Tomography Computed Tomography; Postoperative Complications; Postprandial Period; Potassium Cyanide; Predictive Value of Tests; Prefrontal Cortex; Pregnancy; Prepulse Inhibition; Prevalence; Procalcitonin; Prodrugs; Prognosis; Progression-Free Survival; Proline; Proof of Concept Study; Prospective Studies; Protein Binding; Protein Conformation; Protein Domains; Protein Folding; Protein Multimerization; Protein Sorting Signals; Protein Structure, Secondary; Proton Pump Inhibitors; Protozoan Proteins; Psychometrics; Pulse Wave Analysis; Pyridines; Pyrrolidines; Quality of Life; Quantum Dots; Quinoxalines; Quorum Sensing; Radiopharmaceuticals; Rain; Random Allocation; Randomized Controlled Trials as Topic; Rats; Rats, Sprague-Dawley; Rats, Wistar; RAW 264.7 Cells; Reactive Oxygen Species; Receptor, Angiotensin, Type 1; Receptor, PAR-1; Receptors, CXCR4; Receptors, Estrogen; Receptors, Glucocorticoid; Receptors, Interleukin-1; Receptors, Interleukin-17; Receptors, Notch; Recombinant Fusion Proteins; Recombinant Proteins; Reducing Agents; Reflex, Startle; Regional Blood Flow; Regression Analysis; Reperfusion Injury; Reproducibility of Results; Republic of Korea; Respiratory Tract Diseases; Retrospective Studies; Reverse Transcriptase Inhibitors; Rhinitis, Allergic; Risk Assessment; Risk Factors; Rituximab; RNA, Messenger; RNA, Ribosomal, 16S; ROC Curve; Rosmarinic Acid; Running; Ruthenium; Rutin; Sarcolemma; Sarcoma; Sarcopenia; Sarcoplasmic Reticulum; SARS-CoV-2; Scavenger Receptors, Class A; Schools; Seasons; Seeds; Sequence Analysis, DNA; Severity of Illness Index; Sex Factors; Shock, Cardiogenic; Short Chain Dehydrogenase-Reductases; Signal Transduction; Silver; Singlet Oxygen; Sinusitis; Skin; Skin Absorption; Small Molecule Libraries; Smoke; Socioeconomic Factors; Soil; Soil Microbiology; Solid Phase Extraction; Solubility; Solvents; Spain; Spectrometry, Mass, Electrospray Ionization; Spectroscopy, Fourier Transform Infrared; Speech; Speech Perception; Spindle Poles; Spleen; Sporothrix; Staphylococcal Infections; Staphylococcus aureus; Stereoisomerism; Stomach Neoplasms; Stress, Physiological; Stroke Volume; Structure-Activity Relationship; Substrate Specificity; Sulfonamides; Surface Properties; Surface-Active Agents; Surveys and Questionnaires; Survival Rate; T-Lymphocytes, Cytotoxic; Tandem Mass Spectrometry; Temperature; Tenofovir; Terpenes; Tetracycline; Tetrapleura; Textiles; Thermodynamics; Thiobarbituric Acid Reactive Substances; Thrombin; Thyroid Hormones; Thyroid Neoplasms; Tibial Meniscus Injuries; Time Factors; Tissue Distribution; Titanium; Toluidines; Tomography, X-Ray Computed; Tooth; Tramadol; Transcription Factor AP-1; Transcription, Genetic; Transfection; Transgender Persons; Translations; Treatment Outcome; Triglycerides; Ubiquinone; Ubiquitin-Specific Proteases; United Kingdom; United States; Up-Regulation; Vascular Stiffness; Veins; Ventricular Remodeling; Viral Load; Virulence Factors; Virus Replication; Vitis; Voice; Voice Quality; Wastewater; Water; Water Pollutants, Chemical; Water-Electrolyte Balance; Weather; Wildfires; Wnt Signaling Pathway; Wound Healing; X-Ray Diffraction; Xenograft Model Antitumor Assays; Young Adult; Zoogloea

Experimental studies have suggested the beneficial effects of curcuminoids as natural polyphenols against traumatic brain injury (TBI). The aim of this study was to investigate the effects of supplementation with curcuminoids on inflammatory and oxidative stress biomarkers, clinical outcomes and nutritional status in critically ill patients with TBI. A total of 62 ICU-admitted adult patients with TBI were randomly allocated to receive either a daily dose of 500 mg curcuminoids or matched placebo via enteral nutrition for 7 consecutive days based on stratified block randomization by age and sex. Inflammatory and oxidative stress as well as clinical outcomes and nutritional status of the patients were measured at baseline and at the end of the study. There were no overall group effects regarding to all dependent variables. Compared with baseline, serum levels of IL-6, TNF-α, MCP-1 and CRP were significantly reduced in patients receiving curcuminoids (p < .05) without any significant changes in placebo group; however, changes in the activities of GPx and SOD in serum were not significant between two groups. Moreover, APACHEII and NUTRIC score were significantly improved following curcuminoids consumption in comparison with placebo (p < .05). The findings of this study suggest that short-term supplementation with curcuminoids may have beneficial effects on inflammation, clinical outcomes and nutritional status of critically ill patients with TBI.

Topics: Adult; Biomarkers; Critical Illness; Curcumin; Cytokines; Diarylheptanoids; Dietary Supplements; Double-Blind Method; Humans; Inflammation; Nutritional Status; Oxidative Stress

Topics: Adult; Biomarkers; Curcumin; Dietary Supplements; Double-Blind Method; Female; Humans; Inflammation; Male; Migraine Disorders; Neuroprotective Agents; Oxidative Stress; Quality of Life; Ubiquinone

This study aims to evaluate the analgesic and modulating effect of Curcuma longa and Miconia albicans herbal medicines in knee's osteoarthritis (OA) treatment. This longitudinal study evaluated 24 patients with OA. The patients were divided into three groups: ibuprofen (1200 mg/day), C. longa (1000 mg/day) and M. albicans (1000 mg/day). The medications were applied orally for 30 days. The synovial fluid of the knee joint was collect at the first (day 0) and the last medical (day 30) consultation. The groups treated with herbal medicines presented the same results when compared to Ibuprofen. The comparison of the means of Total WOMAC for M. albicans before and after treatment presented a statistically significant difference (mean day 0 = 57.19; mean day 30 = 31.02) as well as variation of Total WOMAC for C. longa (mean day 0 = 54.79; mean day 30 = 37.08). The WOMAC Total and the VASP were compared, it was found that there was a significant decrease in the means in the C. longa and M. albicans groups, as well as in the Ibuprofen group after treatment. The study demonstrated that the treatment of knee OA with C. longa or M. albicans positively interferes with patients pain and functionality, decreased WOMAC and VASP scores, leading to functional improvement of these patients. This is the first clinical study demonstrating the analgesic and anti-inflammatory effect on knee osteoarthritis from M. albicans comparable to Ibuprofen drug.

Topics: Adult; Aged; Aged, 80 and over; Anti-Inflammatory Agents, Non-Steroidal; Arthralgia; Curcuma; Female; Humans; Ibuprofen; Inflammation; Longitudinal Studies; Male; Melastomataceae; Middle Aged; Osteoarthritis, Knee; Plant Extracts; Treatment Outcome

Although curcumin's effect on head and neck cancer has been studied in vitro and in vivo, to the authors' knowledge its efficacy is limited by poor systemic absorption from oral administration. APG-157 is a botanical drug containing multiple polyphenols, including curcumin, developed under the US Food and Drug Administration's Botanical Drug Development, that delivers the active components to oromucosal tissues near the tumor target.. A double-blind, randomized, placebo-controlled, phase 1 clinical trial was conducted with APG-157 in 13 normal subjects and 12 patients with oral cancer. Two doses, 100 mg or 200 mg, were delivered transorally every hour for 3 hours. Blood and saliva were collected before and 1 hour, 2 hours, 3 hours, and 24 hours after treatment. Electrocardiograms and blood tests did not demonstrate any toxicity.. Treatment with APG-157 resulted in circulating concentrations of curcumin and analogs peaking at 3 hours with reduced IL-1β, IL-6, and IL-8 concentrations in the salivary supernatant fluid of patients with cancer. Salivary microbial flora analysis showed a reduction in Bacteroidetes species in cancer subjects. RNA and immunofluorescence analyses of tumor tissues of a subject demonstrated increased expression of genes associated with differentiation and T-cell recruitment to the tumor microenvironment.. The results of the current study suggested that APG-157 could serve as a therapeutic drug in combination with immunotherapy.. Curcumin has been shown to suppress tumor cells because of its antioxidant and anti-inflammatory properties. However, its effectiveness has been limited by poor absorption when delivered orally. Subjects with oral cancer were given oral APG-157, a botanical drug containing multiple polyphenols, including curcumin. Curcumin was found in the blood and in tumor tissues. Inflammatory markers and Bacteroides species were found to be decreased in the saliva, and immune T cells were increased in the tumor tissue. APG-157 is absorbed well, reduces inflammation, and attracts T cells to the tumor, suggesting its potential use in combination with immunotherapy drugs.

Topics: Absorption, Physiological; Adult; Aged; Antineoplastic Agents; Curcumin; Cytokines; Double-Blind Method; Female; Humans; Inflammation; Male; Microbiota; Middle Aged; Mouth Neoplasms; Polyphenols; Saliva; Tumor Microenvironment

Nonalcoholic fatty liver diseases (NAFLD) is a highly prevalent disease that is closely associated with several cardiometabolic complications. The potential anti-inflammatory role of curcuminoids that have already been reported to reduce hepatic steatosis, in patients with NAFLD was explored in this study.. This double-blind, randomized placebo-controlled trial was conducted for a period of 8 weeks in patients with NAFLD. Subjects (n = 55) were randomly allocated to receive either curcuminoids or placebo. The curcuminoids group received one capsule containing 500 mg curcuminoids (plus 5 mg piperine to increase intestinal absorption) per day for 8 weeks and the control group received matched placebo capsules for the same period. Liver ultrasonography was performed to assess the severity of hepatic steatosis at baseline and the study end. Serum levels of cytokines including interleukin-1α, interleukin-1β, interleukin-2, interleukin-4, interleukin-6, interleukin-8, interleukin-10, tumor necrosis factor-α, monocyte chemoattractant protein-1, interferon γ, vascular endothelial growth factor and epidermal growth factor were measured before and after the intervention.. The two groups were comparable in demographic features at baseline. The results showed that supplementation with curcuminoids could decrease weight compared to the placebo group (p = 0.016) in patients with NAFLD. Curcuminoids supplementation improved the severity of NAFLD according to the ultrasound results (p = 0.002). Moreover, serum concentrations of TNF-α (p = 0.024), MCP-1 (p = 0.008) and EGF (p = 0.0001) were improved by curcuminoids in NAFLD patients.. The results of our study showed that curcumin supplementation can improve serum levels of inflammatory cytokines in subjects with NAFLD and this might be at least partly responsible for the anti-steatotic effects of curcuminoids.

Topics: Adolescent; Adult; Aged; Alkaloids; Benzodioxoles; Curcumin; Diarylheptanoids; Double-Blind Method; Female; Humans; Inflammation; Male; Middle Aged; Non-alcoholic Fatty Liver Disease; Piperidines; Polyunsaturated Alkamides; Young Adult

Hemodialysis (HD) patients are considered as a high-risk population for cardiovascular disease, within which morbidity and mortality have been determined to be associated with dyslipidemia, pro-inflammatory cytokines, increased levels of C-reactive protein (CRP), and adhesion molecules (ICAM-1, VCAM-1). Different markers have been investigated to detect inflammation in hemodialysis patients, as well as the prognostic values of these markers.. The present study aimed to investigate the effect of nano-curcumin (120 mg) over 12 weeks on hs-CRP levels, adhesion molecules (ICAM-1, VCAM-1), and serum lipid profiles on hemodialysis patients in a randomized controlled clinical trial.. The results revealed that the mean serum hs-CRP level in the nano-curcumin group exhibited a decrease by the end of the study, when compared to mean serum hs-CRP level in the placebo group. However, this between-group trend was not found to be statistically significant (P > .05). Nevertheless, a significant difference was determined between the values in the group receiving nano-curcumin, in comparison with the placebo group, at the end of the study (P < .001). Based on the attained results, mean serum levels of VCAM-1 in the nano-curcumin group were significantly reduced at the end of the study, compared with the placebo group (P < .001). Furthermore, the between-group changes comparison showed significant reductions in serum levels of ICAM- 1 in patients treated with nano-curcumin at the end of the study (P < .05). Additionally, though decreases in mean triglycerides, total cholesterol, LDL-C were noted, there were no statistically significant between-group differences (P > .05). Moreover, between-group changes comparison of HDL-C levels and fasting blood sugar did not show any significant changes.. The current study indicates that nano-curcumin may show beneficial effects in lowering inflammation and hs-CRP levels, as well as adhesion molecules (ICAM-1, VCAM-1), in hemodialysis patients. However, the evidence is still insufficient.

Topics: Adult; Aged; Biomarkers; C-Reactive Protein; Cardiovascular Diseases; Curcumin; Double-Blind Method; Female; Humans; Inflammation; Intercellular Adhesion Molecule-1; Linear Models; Lipids; Male; Middle Aged; Multivariate Analysis; Phytotherapy; Plant Preparations; Renal Dialysis

To evaluate the influence of curcumin supplementation on the glycemic profile, inflammatory markers, and oxidative stress in HIV-infected individuals under antiretroviral therapy. This double-blind, crossover, randomized clinical trial was composed of 20 subjects arranged initially into experimental group (n = 10) and placebo group (n = 10) groups, receiving 1,000 mg curcumin/day or microcrystalline cellulose/day, respectively, during a 30-day period and 12-day washout. Subsequently, the groups were switched to follow the crossover design. Fasting glucose and insulin, IL-10, tumor necrosis factor alpha, malonialdehyde, and reduced glutathione were measured. Food consumption was evaluated as a control variable. Descriptive statistics are presented as mean and standard deviation, and inferential analyses were performed from two-way analysis of variance and the magnitude of the effect. No significant improvements were observed in the glycemic, inflammatory, or oxidative stress profiles. Although the mean serum fasting glucose levels and the homeostatic model assessment index presented qualitative improvement in the CG, this result should be interpreted with caution since the observed variation may represent acceptable fluctuation, in addition to the small difference between the means, added to the large variation observed in the standard deviation. Supplementation with curcumin in HIV-infected individuals undergoing antiretroviral therapy and training did not improve the glycemic, inflammatory, or oxidative stress profiles.

Topics: Blood Glucose; Cross-Over Studies; Curcumin; Dietary Supplements; Double-Blind Method; Female; HIV Infections; Humans; Inflammation; Male; Middle Aged; Oxidative Stress; Volunteers

Topics: Altitude Sickness; Animals; Brain Edema; Cell Hypoxia; Curcumin; Disease Models, Animal; Humans; Inflammation; Male; Mice; NF-kappa B; Vascular Endothelial Growth Factor A

This study assessed the effects of curcumin intake on psychological status, markers of inflammation and oxidative damage in patients with type 2 diabetes mellitus (T2DM) and coronary heart disease (CHD).. This randomized, double-blind, placebo-controlled trial was performed in 60 patients with T2DM and CHD, aged 45-85 years with 2- and 3-vessel CHD. Patients were randomized into two groups to receive either 1000 mg/day curcumin (n = 30) or placebo (n = 30) for 12 weeks. Using RT-PCR method, gene expression related to insulin metabolism and inflammatory markers on mononuclear cells from peripheral blood was evaluated.. Curcumin intake significantly decreased Pittsburgh Sleep Quality Index (PSQI) (β -1.27; 95% CI, -2.27, -0.31; P = 0.01) compared to the placebo group. Curcumin intake caused a significant reduction in malondialdehyde (MDA) (β -0.20 μmol/L; 95% CI, -0.36, -0.04; P = 0.01), significant increase in total antioxidant capacity (TAC) (β 75.82 mmol/L; 95% CI, 3.400, 148.25; P = 0.04) and glutathione (GSH) levels (β 63.48 μmol/L; 95% CI, 26.58, 100.37; P = 0.001) when compared with the placebo. Additionally, curcumin intake upregulated peroxisome proliferator-activated receptor gamma (PPAR-γ) (P = 0.01).. Curcumin intake for 12 weeks in patients with T2DM and CHD had beneficial effects on PSQI, TAC, GSH, MDA values, and gene expression of PPAR-γ. This study was retrospectively registered in the Iranian website (www.irct.ir) for registration of clinical trials (http://www.irct.ir: IRCT20170513033941N63).

Topics: Blood Glucose; C-Reactive Protein; Coronary Disease; Curcumin; Diabetes Mellitus, Type 2; Humans; Inflammation; Iran; Oxidative Stress

Curcumin has been shown to reduce exercise-induced oxidative stress (OS) and inflammation. The purpose of this investigation was to examine the effects of curcumin supplementation on OS, inflammation, muscle damage, and muscle soreness. Nineteen males participated in a randomized, double-blinded, placebo-controlled trial to examine the effects of curcumin supplementation (1.5 g/day) compared to a placebo (PLA) following a muscle-damaging protocol (MDP) on OS, inflammation, muscle damage, and soreness. Participants were randomized to two groups, curcumin or placebo group. The MDP was performed before and after supplementation (28 days). Blood was sampled pre- and postexercise and 60 min, 24 h, and 48 h postexercise and analyzed for total antioxidant capacity (TAC), malondialdehyde (MDA), tumor necrosis factor alpha (TNF-α), and creatine kinase (CK). In addition, a visual analog scale (VAS) was used on each blood sample to measure perceived muscle soreness. After supplementation, curcumin significantly blunted CK levels (199.62 U/L) compared to the placebo (287.03 U/L), overall (

Topics: Adolescent; Adult; Creatine Kinase; Curcumin; Double-Blind Method; Exercise; Humans; Inflammation; Male; Malondialdehyde; Muscle, Skeletal; Myalgia; Oxidative Stress; Tumor Necrosis Factor-alpha; Young Adult

Ankylosing spondylitis (AS) is an inflammatory rheumatic disease with increased bone mass in the main sites of inflammation. Regulatory T (Treg) cells have been reported to involve in pathology of AS. This study designed at investigating the effects of nanocurcumin on Treg cell responses in peripheral blood (PB) of AS patients.. Test group including 12 AS patients received nanocurcumin daily for 4 months and control group including 12 patients received placebo. The frequency of Treg was measured by flow cytometry. The expression levels of FoxP3 and several associated microRNAs (miRNAs; miR-27, miR-17, and miR-146a) and cytokines including Interleukin-10 (IL-10), TGF-β, and IL-6 were assessed by real-time polymerase chain reaction. Furthermore, enzyme-linked immunosorbent assay was done to determine the secretion levels of cytokines.. After treatment with nanocurcumin the frequency of Treg cells in AS patients increased significantly. The RT-PCR data indicated that the expression of miR-17 and miR-27 were significantly decreased following nanocurcumin treatment while miR-146a and FoxP3 were significantly increased. Moreover, nanocurcumin-treated group had high levels of IL-10 and TGF-β and low levels of IL-6 production than control group.. The findings suggested that dysregulation of Treg cells in PB influences the AS development and nanocurcumin therapy could regulate the Treg cells, and so could be useful in the treatment of AS and may be other autoimmune diseases. This study is registered with IRCT.ir, number IRCT2017052927520N7.

Topics: Adult; Curcumin; Double-Blind Method; Female; Forkhead Transcription Factors; Humans; Inflammation; Interleukin-10; Interleukin-6; Leukocytes, Mononuclear; Male; MicroRNAs; Middle Aged; Nanoparticles; Spondylitis, Ankylosing; T-Lymphocytes, Regulatory; Transforming Growth Factor beta; Young Adult

Strenuous exercise induces inflammation and muscle damage. Turmeric (Curcuma longa L.) is a widely used spice that exhibits potent anti-inflammatory response and appears to decrease indirect markers of muscle damage. A randomized, double-blind, placebo-controlled trial was conducted to evaluate the effects of Curcuma longa L. extract (CLE) on inflammation and muscle damage after a half-marathon race.. Twenty-eight healthy, normal-weight men were randomly assigned to one of two groups: (1) CLE (3 capsules per day, 500 mg each); or (2) placebo (PLA, 3 capsules per day, 500 mg of microcrystalline cellulose). Participants received the intervention for 4 weeks and immediately before and after the half-marathon race. Creatine kinase, lactate dehydrogenase, alanine aminotransferase, aspartate aminotransferase, myoglobin, interleukins 6 and 10 were assessed at baseline, immediately before, after, and at 2, 24, and 48 h after the half-marathon race.. The half-marathon race increased markers of inflammation and muscle damage. A greater increase in interleukin-10 was observed in the CLE group immediately after the competition compared to the PLA group (7.54 ± 1.45 vs 5.25 ± 0.59 pg/mL; p < 0.05; d = 0.55). Myoglobin concentration was lower 2 h after the race in participants from the CLE group compared to the PLA group (62.10 ± 8.26 vs 107.85 ± 18.45 ng/mL; p = 0.01; d = 0.86).. Curcuma longa L. extract supplementation leads to an increase in IL-10 and decreased myoglobin in recreational male runners after a half-marathon race.. U1111-1179-6335, February 13, 2016.

Topics: Adult; Curcuma; Dietary Supplements; Double-Blind Method; Exercise; Humans; Inflammation; Male; Marathon Running; Muscle, Skeletal; Plant Extracts; Running

Successful management of periodontitis requires treatment strategy that integrates therapies addressing both pathogen and host aspects of disease etiology. To evaluate sub gingivally applied curcumin gel in treatment of chronic periodontitis based on clinical and biochemical parameters.. A randomized, double blind, parallel-group trial was carried out on 30 patients suffering from chronic generalized periodontitis with probing pocket depth≥5mm on at least 4 sites who were then randomly allocated to two groups. Control group was treated with Scaling and Root Planing (SRP) alone while experimental group was treated with SRP followed by subgingival application of curcumin gel. Saliva collection was done and the clinical parameters were recorded at baseline and follow up periods. Saliva analysis for IL-1β was done by ELISA. The statistical differences for the intra-group and intergroup measurements were analyzed by using Mann Whitney test. Spearman's rank correlation coefficient was used to examine the relationship between Interleukin - 1β and clinical parameters.. Study elucidated mild adjunctive benefit of curcumin gel in reduction of gingival inflammation for a limited period of time. Though improvement in other clinical parameters was also greater in subjects treated with curcumin gel, results were not statistically different from those treated with SRP alone. None of the subjects who received curcumin gel experienced any adverse effect.. Within limitations, it can be concluded that single application of curcumin (turmeric) gel has limited added benefit over scaling and root planing in treatment of chronic periodontitis.

Topics: Adult; Aged; Chronic Periodontitis; Curcumin; Dental Scaling; Double-Blind Method; Female; Gels; Humans; Inflammation; Interleukin-1beta; Male; Middle Aged; Root Planing; Saliva; Statistics, Nonparametric; Young Adult

Breast cancer patients receiving hormonal therapies face risks of relapse, increased rates of cardiovascular events, and toxicities of therapy such as aromatase inhibitor (AI)-associated musculoskeletal symptoms (AIMSS). C-reactive protein (CRP), a marker for inflammation, is associated with breast cancer outcomes. We evaluated whether the olive-derived polyphenol hydroxytyrosol combined with omega-3 fatty acids and curcumin would reduce CRP and musculoskeletal symptoms in breast cancer patients receiving adjuvant hormonal therapies.. This prospective, multicenter, open-label, single arm, clinical trial enrolled post-menopausal breast cancer patients (n = 45) with elevated C-reactive protein (CRP) taking predominantly aromatase inhibitors to receive a combination of hydroxytyrosol, omega-3 fatty acids, and curcumin for 1 month. CRP, other inflammation-associated cytokines, and pain scores on the Brief Pain Inventory were measured before therapy, at the end of therapy and 1 month after completion of therapy.. CRP levels declined during the therapy [from 8.2 ± 6.4 mg/L at baseline to 5.3 ± 3.2 mg/L (p = 0.014) at 30 days of treatment], and remained decreased during the additional 1 month off therapy. Subjects with the highest baseline CRP levels had the greatest decrease with the therapy. Pain scores also decreased during the therapy. There were no significant adverse events.. The combination of hydroxytyrosol, omega-3 fatty acids, and curcumin reduced inflammation as indicated by a reduction in CRP and reduced pain in patients with aromatase-induced musculoskeletal symptoms. Longer studies comparing this combination to other anti-inflammatories in larger groups of patients with clinical outcome endpoints are warranted.

Topics: Adult; Aged; Aged, 80 and over; Aromatase Inhibitors; Breast Neoplasms; C-Reactive Protein; Chemotherapy, Adjuvant; Curcumin; Drug Combinations; Fatty Acids, Omega-3; Female; Humans; Inflammation; Middle Aged; Musculoskeletal Pain; Phenylethyl Alcohol; Pilot Projects; Postmenopause; Prospective Studies

We examined the effect of curcumin (CUR) ingestion before or after exercise on changes in muscle damage and inflammatory responses after exercise. We conducted two parallel experiments with different CUR ingestion timings using a double-blind crossover. In Exp. 1, ten healthy men ingested 180 mg d

Topics: Adult; Biomarkers; Creatine Kinase; Cross-Over Studies; Curcumin; Dietary Supplements; Double-Blind Method; Eating; Elbow; Exercise; Humans; Inflammation; Interleukin-8; Isometric Contraction; Male; Muscle, Skeletal; Myalgia; Range of Motion, Articular; Torque

Diabetes mellitus is one of the most common and important metabolic diseases in human. Curcumin, which is a natural polyphenol found in turmeric, can be used in treatment of diabetes complications for its antidiabetic, anti-inflammatory, and antioxidant properties. In this double-blind randomized clinical trial, 44 patients with Type 2 diabetes randomly assigned to curcumin or placebo group. Patients consumed either 1,500-mg curcumin or placebo daily for 10 weeks. Anthropometric measurements were measured at baseline and at the end of the study. Serum concentrations of triglyceride (TG), total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, high-sensitivity C-reactive protein, and adiponectin were determined after 12-hr fasting at the beginning and end of study. The mean serum level of TG decreased in curcumin group compared with baseline (109 ± 36 vs. 124 ± 36; p < 0.05). At the end of study, the mean concentration of high-sensitivity C-reactive protein decreased in the curcumin group compared to the control (2.9 ± 2.9 vs. 3.4 ± 4.2; p < 0.05). The mean serum concentration of adiponectin increased (64 ± 3 vs. 63 ± 4; p < 0.05) in the treatment group compared with the placebo at the end of the study. The results of the current study indicate that curcumin consumption may reduce diabetes complications through decreasing TG level as well as indicators of inflammation.

Topics: Adiponectin; Adult; Aged; Antioxidants; C-Reactive Protein; Cholesterol, HDL; Cholesterol, LDL; Curcuma; Curcumin; Diabetes Mellitus, Type 2; Dietary Supplements; Double-Blind Method; Fasting; Female; Humans; Inflammation; Lipids; Male; Middle Aged; Triglycerides

It is well known that there is a strong linkage between obesity, systemic low-grade inflammation, and oxidative stress in the pediatric population. Possible strategies that might control obesity and its relevant problems in this crucial group are of utmost importance. Therefore, the aim of this study was to evaluate the effects of curcumin supplements on inflammation, oxidative stress, and chemerin levels in adolescent girls.. Totally, 60 overweight and obese adolescent girls were randomly assigned to either placebo or intervention group in a randomized placebo-controlled parallel trial design. Adolescents consumed one 500-mg curcumin or placebo per day along with a slight weight loss diet for 10 weeks. High-sensitive C-reactive protein (hs-CRP), interleukin 6 (IL-6), total antioxidant capacity (TAC), malondialdehyde (MDA), chemerin levels, and anthropometric measurements were assessed at the beginning and end of the trial.. Curcumin supplementation had a significant effect on IL-6 levels and oxidative stress markers including TAC and MDA in crude model. After controlling the effects of confounders, curcumin supplementation had a substantial effect on inflammation (hs-CRP and IL-6) and oxidative stress (TAC) marker of adolescents.. Ten weeks of curcumin supplementation had beneficial effects on inflammation and oxidative stress markers among postpubescent overweight and obese girl adolescents.

Topics: Adolescent; Curcumin; Female; Humans; Inflammation; Obesity; Overweight; Oxidative Stress

The aim of the present study was to evaluate the effects of curcumin supplementation on inflammatory indices, and hepatic features in patients with non-alcoholic fatty liver disease (NAFLD).. Fifty patients with NAFLD were randomized to receive lifestyle modification advice plus either 1500 mg curcumin or the same amount of placebo for 12 weeks.. Curcumin supplementation was associated with significant decrease in hepatic fibrosis (p < 0.001), and nuclear factor-kappa B activity (p < 0.05) as compared with the baseline. Hepatic steatosis and serum level of liver enzymes, and tumor necrosis-α (TNF-α) significantly reduced in both groups (p < 0.05). None of the changes were significantly different between two groups.. Our results indicated that curcumin supplementation plus lifestyle modification is not superior to lifestyle modification alone in amelioration of inflammation.. IRCT20100524004010N24, this trial was retrospectively registered on May 14, 2018.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Curcumin; Female; Humans; Inflammation; Liver; Liver Function Tests; Male; Middle Aged; NF-kappa B; Non-alcoholic Fatty Liver Disease; Risk Reduction Behavior; Treatment Outcome; Tumor Necrosis Factor-alpha

Curcuminoids have been shown to reduce glycemia and related complications in diabetes. In the present study, we evaluated the impact of curcuminoids plus piperine administration on glycemic, hepatic and inflammatory biomarkers in type 2 diabetes (T2D) patients.. T2D patients aged 18-65 years were enrolled in a randomized double-blind placebo-controlled trial and randomly allocated to standard-of-care treatment and dietary advises plus either curcuminoids (daily dose of 500 mg/day co-administered with piperine 5 mg/day) or placebo for a period of 3 months. Glycemic, hepatic and inflammatory parameters were measured at baseline and final conditions.. A total of 100 subjects (50 in each group) completed the 3-month period of trial. A significant reduction was found in serum levels of glucose (-9±16 mg/dL vs. -3±11 mg/dL in curcuminoids and placebo groups, respectively; p=0.048), C-peptide (-0.6±0.8 ng/mL vs. 0.02±0.6 ng/mL; p<0.001) and HbA1c (-0.9±1.1% vs. -0.2±0.5%; p<0.001) after curcuminoids supplementation versus placebo group. Additionally, participants in the intervention group showed lower serum alanine aminotransferase (-2±6 vs. -1±5; p=0.032) and aspartate aminotransferase (-3±5 vs. -0.3±4; p=0.002) levels compared with the placebo group. Finally, no significant differences in high-sensitivity C-reactive protein (hs-CRP) concentrations were observed between curcuminoids and placebo groups (p>0.05).. The results of the present trial revealed a beneficial effect of curcuminoids plus piperine supplementation on glycemic and hepatic parameters but not on hs-CRP levels in T2D patients.

Topics: Adolescent; Adult; Aged; Alanine Transaminase; Alkaloids; Antioxidants; Aspartate Aminotransferases; Benzodioxoles; Biomarkers; Blood Glucose; C-Reactive Protein; Curcumin; Diabetes Mellitus, Type 2; Dietary Supplements; Double-Blind Method; Female; Humans; Inflammation; Male; Middle Aged; Oxidative Stress; Piperidines; Polyunsaturated Alkamides; Young Adult

High-fat meals induce postprandial inflammation. Resveratrol is a polyphenol known to prevent comorbidities associated with cardiovascular disease and exerts an anti-inflammatory action. There is also an increasing body of evidence supporting the role of curcumin, a polyphenol from the curcuminoid family, as a modulator of proinflammatory processes.. The objectives of this study were to investigate the following: 1) the bioavailability of resveratrol consumed in combination with curcumin after consumption of a high-fat meal; and 2) the acute combined effects of this combination on the postprandial inflammatory response of subjects with abdominal obesity.. In a double blind, crossover, randomized, placebo-controlled study, 11 men and 11 postmenopausal women [mean ± SD age: 62 ± 5 y; mean ± SD body mass index (in kg/m2): 29 ± 3] underwent a 6-h oral fat tolerance test on 2 occasions separated by 1-2 wk: once after consumption of a dietary supplement (200 mg resveratrol and 100 mg curcumin, Res/Cur) and once after consumption of a placebo (cellulose). Plasma concentrations of total resveratrol and its major metabolites as well as inflammatory markers, adhesion molecules, and whole blood NFκB1 and PPARA gene expression were measured during both fat tolerance tests.. Kinetics of resveratrol and identified metabolites revealed rapid absorption patterns but also relatively limited bioavailability based on free resveratrol concentrations. Supplementation with Res/Cur did not modify postprandial variations in circulating inflammatory markers (C-reactive protein, IL-6, IL-8, monocyte chemoattractant protein-1) and adhesion molecules [soluble E-selectin, soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble intercellular adhesion molecule-1] compared to placebo (PTreatment×Time > 0.05). However, Res/Cur significantly decreased the cumulative postprandial response of sVCAM-1, compared to placebo (incremental area under the curve -4643%, P = 0.01). Postprandial variations of whole-blood PPARA and NFKB1 gene expression were not different between Res/Cur and placebo treatments.. Acute supplementation with Res/Cur has no impact on the postprandial inflammation response to a high-fat meal in abdominally obese older adults. Further studies are warranted to examine how resveratrol and curcumin may alter the vascular response to a high-fat meal. This trial was registered at clinicaltrials.gov as NCT01964846.

Topics: Aged; Anti-Inflammatory Agents; Area Under Curve; Biological Availability; C-Reactive Protein; Chemokine CCL2; Cross-Over Studies; Curcumin; Dietary Fats; Dietary Supplements; Double-Blind Method; Drug Combinations; Female; Humans; Inflammation; Inflammation Mediators; Interleukins; Male; Middle Aged; Obesity, Abdominal; Plant Extracts; Postprandial Period; PPAR alpha; Resveratrol

Curcumin is a turmeric-contained active ingredient that has been proven to be effective in treating pain and inflammation due to its analgesic as well as anti-inflammation potential. Odontectomy, on the other hand, has been well known for its post-procedure acute inflammation pain. The aim of the current study was to evaluate the efficacy of curcuminoid in treating acute inflammation post-operative pain in the post-surgical removal of impacted third molars patients. Ninety (44 males; 46 females) participants were recruited in this randomised controlled trial and randomly assigned to the control group (those who consumed mefenamic acid) or the experimental group (those who consumed curcumin). Numeric rating scale (NRS) was used as an evaluation tool to evaluate the intensity of the pain experienced by the participants. Pain evaluation was performed immediately after anaesthesia effect disappeared (T

Topics: Adolescent; Adult; Aged; Analgesics; Anti-Inflammatory Agents, Non-Steroidal; Curcumin; Female; Humans; Inflammation; Male; Middle Aged; Molar, Third; Pain, Postoperative; Tooth Extraction; Tooth, Impacted; Treatment Outcome; Young Adult

Chronic kidney disease (CKD) is a progressive disease with an inverse relationship between kidney function and levels of inflammation and oxidative stress. Curcumin and Boswellia serrata have been reported to exert anti-inflammatory effects on the cyclooxygenase and lipoxygenase pathways. Therefore, the purpose of this study was to study the effects of a supplement containing curcumin and B. serrata on eicosanoid derivatives in early stage CKD patients who had not initiated hemodialysis.. Sixteen patients with stage 2 and stage 3 CKD (56.0 ± 16.0 years, 171.4 ± 11.9 cm, 99.3 ± 20.2 kg) were randomized into a treatment group with curcumin and B. serrata or a placebo group. The dependent variables prostaglandin E. A significant group effect (p = 0.05), and a trend for Group × Time interaction (p = 0.056) were detected for PGE. This is the first article of baseline levels of the dependent variables in early stage CKD, and the first article to show a significant effect of these supplements on PGE

Topics: Adult; Aged; Anti-Inflammatory Agents; Boswellia; Curcumin; Dietary Supplements; Eicosanoids; Humans; Inflammation; Middle Aged; Pilot Projects; Plant Extracts; Renal Insufficiency, Chronic

Despite advances in prevention of inflammatory milieu with different anti-inflammatory modalities in hemodialysis patients the rate of inflammatory markers in this population are still high. Inflammation is considered as a major player in uremia associated with morbidity and mortality in hemodialysis patients. The aim of this study was to evaluate the turmeric s effects on reduction of inflammatory markers in hemodialysis patients.. Hemodialysis patients over 18 years were recruited after fulfilling the inclusion criteria. Seventy-one hemodialysis patients were randomized into two groups: the trial group (n = 35) and the controls (n = 36); a randomization numeric table was used for allocation sequence. Trial group received turmeric and control group received placebo for 12 weeks. Biochemical determinations included levels of serum albumin (Alb), potassium (K), blood urea nitrogen (BUN), serum creatinine (Cr), IL-6 level, TNF-α, and liver function tests and hs-CRP at the start and end of the study were measured.. Although there was a significant reduction in hs-CRP level, IL-6 level and TNF-α level in turmeric group (p = 0.002, p = 0.001, p = 0.001), there was no statistical difference between intervention and control groups. Albumin level was significantly increased in turmeric group (p = 0.001) and no meaningful changes were seen in potassium or liver function tests neither within nor between groups.. Programmed ingestion of turmeric has no adverse effects and reduces plasma level of hs-CRP, IL-6 and TNF-α accompanying with increases albumin levels in hemodialysis patients. Turmeric can be considered as an effective anti-inflammatory supplement in hemodialysis patients.

Topics: Adult; Aged; Biomarkers; C-Reactive Protein; Curcuma; Curcumin; Dietary Supplements; Double-Blind Method; Female; Humans; Inflammation; Interleukin-6; Male; Middle Aged; Renal Dialysis; Serum Albumin; Tumor Necrosis Factor-alpha

Curcuminoids are poorly bioavailable, but potentially lipid- and inflammation-lowering phytochemicals. We hypothesized that curcuminoids, when administered as a micellar formulation with hundredfold enhanced bioavailability, decrease blood lipids and inflammation in subjects with moderately elevated cholesterol and C-reactive protein concentrations.. We carried out a randomized, double-blind, crossover study (4-wk washout phase) with 42 subjects consuming 294 mg curcuminoids per day (as micelles) or placebo for 6 wk. At the beginning, after 3 wk and at the end (6 wk) of each intervention, we collected fasting blood samples to determine curcuminoids, blood lipids, and markers of inflammation, glucose and iron homeostasis, and liver toxicity. Daily ingestion of 98 mg micellar curcuminoids with each principal meal for as little as 3 wk resulted in fasting curcuminoid plasma concentrations of 49 nmol/L. Neither blood lipids, nor markers of inflammation, glucose and iron homeostasis, or liver enzymes differed between curcuminoid and placebo interventions.. Consumption of 98 mg of highly bioavailable curcuminoids with each principal meal sufficed to achieve curcuminoid accumulation in the blood, was safe, and did not alter blood lipids, inflammation, glucose, or iron homeostasis in healthy subjects with slightly elevated blood cholesterol and C-reactive protein.

Topics: Adult; Aged; Alanine Transaminase; Anti-Inflammatory Agents; Aspartate Aminotransferases; Biological Availability; Biomarkers; Body Mass Index; Body Weight; C-Reactive Protein; Cholesterol; Cross-Over Studies; Curcuma; Curcumin; Double-Blind Method; Female; Homeostasis; Humans; Hyperlipidemias; Inflammation; Interleukin-6; Iron; Male; Micelles; Middle Aged; Phytochemicals; Plant Extracts; Triglycerides

Osteoarthritis (OA) is a degenerative joint disease associated with inflammation. The present study aimed to determine changes in serum levels of inflammatory biomarkers in OA patients whose clinical symptoms were improved as a result of supplementation with curcuminoids.. This study was a randomized double-blind placebo-control parallel-group clinical trial in which 40 subjects with mild-to-moderate degree knee OA were randomly allocated to receive either pure curcuminoids (1,500 mg/day in 3 divided doses; n=19) or matched placebo (n=21) for 6 weeks. In order to enhance the bioavailability of curcuminoids, piperine (15 mg/day) was added to the treatment regimen. Serum levels of interleukins 4 (IL-4) and 6 (IL-6), tumor necrosis factor-α (TNF-α), transforming growth factor-β (TGF-β) and high-sensitivity C-reactive protein (hs-CRP), together with erythrocyte sedimentation rate (ESR) were determined at baseline as well as at the end of trial.. Serum concentrations of IL-4 (p=0.001), IL-6 (p=0.006) and hs-CRP (p=0.004) were significantly reduced in the curcuminoid group whilst serum levels of TNF-α and TGF-β and mean ESR remained unaltered by the end of trial (p>0.05). In the placebo group, serum concentrations of IL-4 (p=0.001), IL-6 (p=0.003), TNF-α (p=0.003) and TGF-β (p=0.005) were significantly reduced but mean hs-CRP and ESR values remained statistically unchanged (p>0.05). Comparison of the magnitude of changes in the evaluated inflammatory biomarkers did not indicate any significant difference between the study groups (p>0.05).. Significant improvement in clinical symptoms of OA in curcuminoid-treated subjects cannot be attributed to the systemic anti-inflammatory effects of these phytochemicals.

Topics: Aged; Anti-Inflammatory Agents; Biomarkers; Curcumin; Cytokines; Double-Blind Method; Female; Humans; Inflammation; Male; Middle Aged; Osteoarthritis, Knee; Treatment Outcome

Pulmonary problems are among the most frequent chronic complications of sulfur mustard (SM) intoxication and are often accompanied by deregulated production of pro-inflammatory cytokines. Curcuminoids, comprising curcumin, demethoxycurcumin and bisdemethoxycurcumin, are phytochemicals with remarkable anti-inflammatory properties that are derived from dried rhizomes of the plant Curcuma longa L. (turmeric). The present pilot study aimed to investigate the clinical effects of supplementation with curcuminoids on markers of pulmonary function and systemic inflammation in SM-intoxicated subjects. In a randomized double-blind placebo-controlled trial, 89 male subjects who were suffering from chronic SM-induced pulmonary complications were recruited and assigned to either curcuminoids (500 mg TID per oral; n=45) or placebo (n=44) for a period of 4 weeks. Efficacy measures were changes in the spirometric parameters (FVC, FEV1, FEV1/FVC) and serum levels of inflammatory mediators including interleukins 6 (IL-6) and 8 (IL-8), tumor necrosis factor-α (TNFα), transforming growth factor-β (TGFβ), high-sensitivity C-reactive protein (hs-CRP), calcitonin gene related peptide (CGRP), substance P and monocyte chemotactic protein-1 (MCP-1). 78 subjects completed the trial. Although FEV1 and FVC remained comparable between the groups, there was a greater effect of curcuminoids vs. placebo in improving FEV1/FVC (p=0.002). Curcuminoids were also significantly more efficacious compared to placebo in modulating all assessed inflammatory mediators: IL-6 (p<0.001), IL-8 (p=0.035), TNFα (p<0.001), TGFβ (p<0.001), substance P (p=0.016), hs-CRP (p<0.001), CGRP (p<0.001) and MCP-1 (p<0.001). Curcuminoids were safe and well-tolerated throughout the trial. Short-term adjunctive therapy with curcuminoids can suppress systemic inflammation in patients suffering from SM-induced chronic pulmonary complications.

Topics: Adult; Anti-Inflammatory Agents; Chemical Warfare Agents; Chronic Disease; Curcumin; Cytokines; Diarylheptanoids; Double-Blind Method; Forced Expiratory Volume; Humans; Inflammation; Inflammation Mediators; Lung Diseases; Male; Middle Aged; Mustard Gas; Pilot Projects; Treatment Outcome; Vital Capacity

Oxidative stress and inflammation have been proposed as emerging components of metabolic syndrome (MetS). Curcuminoids are natural polyphenols with strong antioxidant and anti-inflammatory properties.. To study the effectiveness of supplementation with a bioavailable curcuminoid preparation on measures of oxidative stress and inflammation in patients with MetS. Our secondary aim was to perform a meta-analysis of data from all randomized controlled trials in order to estimate the effect size of curcuminoids on plasma C-reactive protein (CRP) concentrations.. In this randomized double-blind placebo-controlled trial, 117 subjects with MetS (according to the NCEP-ATPIII diagnostic criteria) were randomly assigned to curcuminoids (n = 59; drop-outs = 9) or placebo (n = 58; drop-outs = 8) for eight weeks. Curcuminoids were administered at a daily dose of 1 g, and were co-supplemented with piperine (10 mg/day) in order to boost oral bioavailability. Serum activities of superoxide dismutase (SOD) and concentrations of malondialdehyde (MDA) and CRP were measured at baseline and at study end. Regarding the importance of CRP as a risk marker and risk factor of cardiovascular disease, a random-effects meta-analysis of clinical trials was performed to estimate the overall impact of curcuminoid therapy on circulating concentrations of CRP. The robustness of estimated effect size was evaluated using leave-one-out sensitivity analysis.. Supplementation with curcuminoid-piperine combination significantly improved serum SOD activities (p < 0.001) and reduced MDA (p < 0.001) and CRP (p < 0.001) concentrations compared with placebo. Quantitative data synthesis revealed a significant effect of curcuminoids vs. placebo in reducing circulating CRP concentrations (weighed mean difference: -2.20 mg/L; 95% confidence interval [CI]: -3.96, -0.44; p = 0.01). This effect was robust in sensitivity analysis.. Short-term supplementation with curcuminoid-piperine combination significantly improves oxidative and inflammatory status in patients with MetS. Curcuminoids could be regarded as natural, safe and effective CRP-lowering agents.

Topics: Adult; Alkaloids; Anti-Inflammatory Agents; Antioxidants; Benzodioxoles; Biological Availability; Blood Pressure; Body Mass Index; C-Reactive Protein; Curcumin; Databases, Factual; Dietary Supplements; Double-Blind Method; Female; Humans; Inflammation; Male; Malondialdehyde; Meta-Analysis as Topic; Metabolic Syndrome; Middle Aged; Oxidative Stress; Piperidines; Polyunsaturated Alkamides; Superoxide Dismutase

Oral curcumin decreases inflammatory cytokines and increases muscle regeneration in mice.. To determine effects of curcumin on muscle damage, inflammation and delayed onset muscle soreness (DOMS) in humans.. Seventeen men completed a double-blind randomized-controlled crossover trial to estimate the effects of oral curcumin supplementation (2.5 g twice daily) versus placebo on single-leg jump performance and DOMS following unaccustomed heavy eccentric exercise. Curcumin or placebo was taken 2 d before to 3 d after eccentric single-leg press exercise, separated by 14-d washout. Measurements were made at baseline, and 0, 24 and 48-h post-exercise comprising: (a) limb pain (1-10 cm visual analogue scale; VAS), (b) muscle swelling, (c) single-leg jump height, and (d) serum markers of muscle damage and inflammation. Standardized magnitude-based inference was used to define outcomes.. At 24 and 48-h post-exercise, curcumin caused moderate-large reductions in pain during single-leg squat (VAS scale -1.4 to -1.7; 90 %CL: ±1.0), gluteal stretch (-1.0 to -1.9; ±0.9), squat jump (-1.5 to -1.1; ± 1.2) and small reductions in creatine kinase activity (-22-29 %; ±21-22 %). Associated with the pain reduction was a small increase in single-leg jump performance (15 %; 90 %CL ± 12 %). Curcumin increased interleukin-6 concentrations at 0-h (31 %; ±29 %) and 48-h (32 %; ±29 %) relative to baseline, but decreased IL-6 at 24-h relative to post-exercise (-20 %; ±18 %).. Oral curcumin likely reduces pain associated with DOMS with some evidence for enhanced recovery of muscle performance. Further study is required on mechanisms and translational effects on sport or vocational performance.

Topics: Adolescent; Adult; Anti-Inflammatory Agents, Non-Steroidal; Cross-Over Studies; Curcumin; Dietary Supplements; Double-Blind Method; Exercise; Humans; Inflammation; Interleukin-6; Male; Myalgia; Pain; Pain Measurement; Physical Education and Training; Psychomotor Performance; Treatment Outcome; Weight Lifting; Young Adult

Curcumin has a therapeutic potential in treating diabetic kidney disease (DKD) while potential mechanisms underlining this beneficial effect remain to be elucidated. In the present study, curcumin intervention was performed in patients with Type II diabetes mellitus (T2DM) by oral intake of curcumin at the dose of 500 mg/day for a period of 15-30 days. Nephritic excretion of urinary micro-albumin (U-mAlb) and blood metabolic indexes were assessed before and after this intervention. In addition, the lipid oxidation index, malondialdehyde (MDA) in plasma and the status of anti-oxidative Nrf2 system in blood lymphocytes were measured. The effect of curcumin on inflammation was assessed by measuring plasma lipopolysaccharide (LPS) content and inflammatory signaling protein in blood lymphocytes. A self-comparison method was used for assessing statistical significances of these measurements. Here we show that curcumin intervention markedly attenuated U-mAlb excretion without affecting metabolic control of participated patients. In addition, curcumin reduced plasma MDA level with enhanced the Nrf2 system specifically regulated protein, NAD(P)H quinone oxidoreductase 1 (NQO-1) together with other anti-oxidative enzymes in patients' blood lymphocytes. Furthermore, we observed reduced plasma LPS content and increased IκB, an inhibitory protein on inflammatory signaling in patient's lymphocytes after curcumin administration. Finally, several gut bacterials important for maintaining gut barrier integrity and function were upregulated by curcumin.In conclusion, short-term curcumin intervention ablates DKD progress with activating Nrf2 anti-oxidative system and anti-inflammatory efficacies in patients with T2DM.

Topics: Aged; Aged, 80 and over; Albuminuria; Curcumin; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Female; Humans; Inflammation; Lipopolysaccharides; Lymphocytes; Male; Middle Aged; NAD(P)H Dehydrogenase (Quinone); NF-E2-Related Factor 2; Signal Transduction

Curcuminoids are bioactive polyphenolics with potent antiinflammatory properties. Although several lines of in vitro and preclinical evidence suggest potent anticancer effects of curcuminoids, clinical findings have not been conclusive. The present randomized double-blind placebo-controlled trial aimed to evaluate the efficacy of curcuminoids as adjuvant therapy in cancer patients. Eighty subjects with solid tumors who were under standard chemotherapy regimens were randomly assigned to a bioavailability-boosted curcuminoids preparation (180 mg/day; n = 40) or matched placebo (n = 40) for a period of 8 weeks. Efficacy measures were changes in the health-related quality of life (QoL) score (evaluated using the University of Washington index) and serum levels of a panel of mediators implicated in systemic inflammation including interleukins 6 (IL-6) and 8 (IL-8), TNF-α, transforming growth factor-β (TGFβ), high-sensitivity C-reactive protein (hs-CRP), calcitonin gene-related peptide (CGRP), substance P and monocyte chemotactic protein-1 (MCP-1). Curcuminoid supplementation was associated with a significantly greater improvement in QoL compared with placebo (p < 0.001). Consistently, the magnitude of reductions in TNF-α (p < 0.001), TGFβ (p < 0.001), IL-6 (p = 0.061), substance P (p = 0.005), hs-CRP (p < 0.001), CGRP (p < 0.001) and MCP-1 (p < 0.001) were all significantly greater in the curcuminoids versus placebo group. In contrast, the extent of reduction in serum IL-8 was significantly greater with placebo versus curcuminoids (p = 0.012). Quality of life variations were associated with changes in serum TGFβ levels in both correlation and regression analyses. Adjuvant therapy with a bioavailable curcuminoid preparation can significantly improve QoL and suppress systemic inflammation in patients with solid tumors who are under treatment with standard chemotherapy protocols.

Topics: Adult; Aged; Biological Availability; C-Reactive Protein; Calcitonin Gene-Related Peptide; Chemokine CCL2; Chemotherapy, Adjuvant; Curcuma; Curcumin; Double-Blind Method; Female; Humans; Inflammation; Interleukin-6; Interleukin-8; Iran; Male; Middle Aged; Neoplasms; Quality of Life; Tumor Necrosis Factor-alpha

Chronic kidney disease (CKD) is characterized by a continuous reduction in kidney function, increased inflammation, and reduced antioxidant capacity. The objective of this study was to assess the effects of a herbal supplement on systemic inflammation and antioxidant status in non-dialysis CKD patients. Sixteen patients with CKD (56.0±16.0 yrs, 171.4±11.9 cm, 99.3±20.2 kg) were randomly chosen to receive a herbal supplement composed of Curcuma longa and Boswellia serrata, or placebo. Plasma levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), glutathione peroxidase (GPx), and serum C-reactive protein (CRP) were measured at baseline and 8 weeks. Baseline data demonstrated elevated inflammation and low antioxidant levels. A significant time effect (p=0.03) and time x compliance interaction effect (p=0.04) were observed for IL-6. No significant differences were observed for any other variables. This study demonstrates that mild and moderate CKD is associated with chronic inflammation and low antioxidant activity. Systemic inflammation and impaired antioxidant status may be greater in CKD populations with multiple comorbidities. Curcumin and Boswellia serrata are safe and tolerable and helped to improve the levels of an inflammatory cytokine.

Topics: Adult; Aged; Anti-Inflammatory Agents; Antioxidants; Boswellia; C-Reactive Protein; Curcuma; Dietary Supplements; Drug Combinations; Glutathione Peroxidase; Humans; Inflammation; Interleukin-6; Middle Aged; Oxidative Stress; Phytotherapy; Plant Extracts; Renal Insufficiency, Chronic; Tumor Necrosis Factor-alpha

Red pepper spice (RP) and turmeric (TM) are used as flavorings in foods and for medicinal purposes. Utilizing a randomized, doubled-blinded, placebo-controlled, crossover design (2-week washout), 4-week supplementation with RP (1 g/d) or TM (2.8 g/d) was tested for influences on inflammation and oxidative stress in 62 overweight/obese (body mass index ≥ 27 kg/m²) females (40-75 years) with systemic inflammation (C-reactive protein, CRP ≥ 2 mg/l). Overnight, fasted blood samples were collected pre- and post-supplementation, and analyzed for oxidative stress (F₂-isoprostanes, oxidized low density lipoprotein), inflammation (CRP and seven inflammatory cytokines), and metabolic profiles using gas chromatography-mass spectrometry with multivariate partial least square discriminant analysis (PLS-DA). Pre- to post-supplementation measures of inflammation and oxidative stress for both RP and TM did not differ when compared to placebo (all interaction effects, P > 0.05), and global metabolic difference scores calculated through PLS-DA were non-significant (both spices, Q²Y < 0.40). These data indicate that 4-week supplementation with RP or TM at culinary levels does not alter oxidative stress or inflammation in overweight/obese females with systemic inflammation, or cause a significant shift in the global metabolic profile.

Topics: Adult; Aged; Biomarkers; Blood Pressure; Body Composition; Body Mass Index; C-Reactive Protein; Capsicum; Cross-Over Studies; Curcuma; Cytokines; Dietary Supplements; Double-Blind Method; F2-Isoprostanes; Female; Humans; Inflammation; Lipoproteins, LDL; Metabolomics; Middle Aged; Overweight; Oxidative Stress; Plant Extracts; Spices

Among obesity-associated disorders, low-grade inflammation has been described. The putative therapeutic properties of citrus and curcumin polyphenols could be associated with their anti-inflammatory properties. Two diets supplemented either with hesperidin (0.05 %) and naringin (0.1 %) from citrus extract or with highly bioavailable curcumin from Curcuma longa extract (0.09 %) were fed to eight obese cats for two 8-week periods (cross-over study design) while maintaining animals in an obese state. Plasma acute-phase protein (APP; α1-acid glycoprotein (AGP), serum amyloid A and haptoglobin) levels were assessed before and at the end of each test period. TNF-α, IL-1β, IL-2, IL-4, IL-5, IL-10, IL-12, IL-18, transforming growth factor-β, interferon (IFN)-γ mRNA levels were determined in peripheral blood mononuclear cells (PBMC) by real-time PCR. Compared with pre-study values, supplementation with citrus polyphenols resulted in lower plasma AGP and haptoglobin concentrations, while that with curcumin resulted in lower plasma AGP concentration. There were no differences between the supplementations. TNF-α, IL-1β, IL-4, IL-5, IL-10, IL-12, IL-18, transforming growth factor-β, mRNA levels remained unaffected by either dietary supplementation. In contrast, IFN-γ and IL-2 mRNA levels were lower at the end of the citrus and the curcumin supplementation, respectively. There were no differences between the supplementations. The present study results show a slight effect of citrus and curcumin supplementation on inflammatory markers expressed by PBMC, and a decreased concentration of APP, which are mainly expressed by the liver. This would confirm that hesperidin and naringin or highly bioavailable curcumin extract have beneficial effects, targeted in the liver and could improve the obesity-related inflammatory state.

Topics: Acute-Phase Proteins; Animals; Cat Diseases; Cats; Citrus; Cross-Over Studies; Curcumin; Cytokines; Female; Flavanones; Gene Expression Regulation; Hesperidin; Inflammation; Leukocytes, Mononuclear; Male; Obesity; RNA, Messenger

A proprietary complex of curcumin with soy phosphatidylcholine (Meriva®, Indena SpA) was evaluated in a registry study to define its efficacy in 50 patients with osteoarthritis (OA) at dosages corresponding to 200 mg curcumin per diem.. OA signs/symptoms were evaluated by the WOMAC scores. Mobility was studied by walking performance (treadmill), and inflammatory status was assessed by measurements of C-reactive protein (CRP).. After three months of treatment, the global WOMAC score decreased by 58% (P<0.05), walking distance in the treadmill test was prolonged from 76 m to 332 m (P<0.05), and CRP levels decreased from 168 +/- 18 to 11.3 +/-. 4.1 mg/L in the subpopulation with high CRP. In comparison, the control group experienced only a modest improvement in these parameters (2% in the WOMAC score, from 82 m to 129 m in the treadmill test, and from 175 +/- 12.3 to 112 +/- 22.2 mg/L in the CRP plasma concentration), while the treatment costs (use of anti-inflammatory drugs, treatment and hospitalization) were reduced significantly in the treatment group.. These results show that Meriva® is clinically effective in the management and treatment of osteoarthritis and suggest that the increased stability and better absorption of curcumin induced by complexation with phospholipids have clinical relevance, setting the stage for larger and more prolonged studies.

Topics: Adult; C-Reactive Protein; Curcumin; Drug Synergism; Edema; Female; Glycine max; Humans; Inflammation; Male; Middle Aged; Osteoarthritis, Knee; Phosphatidylcholines; Treatment Outcome; Walking

Hyperglycaemia leads to increased oxidative stress resulting in endothelial dysfunction. ACE inhibitors, antioxidants and HMG-CoA reductase inhibitors (statins) have been shown to improve endothelial function. The aim of this study was to compare the effects of NCB-02 (a standardized preparation of curcuminoids), atorvastatin and placebo on endothelial function and its biomarkers in patients with type 2 diabetes mellitus.. A total of 72 patients with type 2 diabetes were randomized to receive NCB-02 (two capsules containing curcumin 150 mg twice daily), atorvastatin 10 mg once daily or placebo for 8 weeks. Endothelial function assessment was performed at baseline and post-treatment using digital volume plethysmography (salbutamol [albuterol] challenge test) to measure change in reflective index, an indicator of arterial vascular tone. Blood samples were similarly collected at baseline and post-treatment for estimations of malondialdehyde, endothelin-1 (ET-1), interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNFalpha). Pre-and post-treatment safety assessments were also conducted. ANOVA and paired t-test evaluations were used for comparison.. A total of 67 patients completed the study. At baseline, there was no significant difference in the various parameters tested. In all three groups, the change in reflective index at baseline was <6% as assessed by the salbutamol challenge test, indicating the presence of endothelial dysfunction. Compared with baseline, there was a significant improvement in endothelial function after treatment with atorvastatin (mean +/- SD: -3.63 +/- 3.17% vs -8.95 +/- 6.80%, respectively) and NCB-02 (-2.69 +/- 3.02% vs -8.19 +/- 5.73%, respectively). Similarly, patients receiving atorvastatin or NCB-02 showed significant reductions in the levels of malondialdehyde, ET-1, IL-6 and TNFalpha. No significant improvements were obtained in patients administered placebo.. NCB-02 had a favourable effect, comparable to that of atorvastatin, on endothelial dysfunction in association with reductions in inflammatory cytokines and markers of oxidative stress. Further studies are needed to evaluate the potential long-term effects of NCB-02 and its combination with other herbal antioxidants.

Topics: Adrenergic beta-Agonists; Adult; Albuterol; Atorvastatin; Biomarkers; Blood Glucose; Cholesterol; Curcumin; Diabetes Mellitus, Type 2; Double-Blind Method; Endothelium, Vascular; Female; Glycated Hemoglobin; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Inflammation; Male; Middle Aged; Oxidative Stress; Pyrroles; Triglycerides

A new model for evaluating nonsteroidal anti-inflammatory drugs (NSAIDs) is described. In this model of postoperative inflammation, the anti-inflammatory activity of curcumin (diferuloyl methane) was investigated in comparison with phenylbutazone and placebo. Phenylbutazone and curcumin produced a better anti-inflammatory response than placebo.

Topics: Adolescent; Adult; Aged; Anti-Inflammatory Agents, Non-Steroidal; Catechols; Clinical Trials as Topic; Curcumin; Double-Blind Method; Humans; Inflammation; Male; Middle Aged; Phenylbutazone; Postoperative Complications; Random Allocation

Dramatically increased glycolysis has been found in inflamed joints in rheumatoid arthritis (RA) due to the increased demand for energy and biosynthetic precursors to support the expansion of inflammation. Therefore, regulating the elevated glycolysis level in RA progress might hold potential to achieve inflammation remission. 2-deoxy-D-glucose (2-DG) is a well-characterized glycolysis inhibitor. However, the rapid clearance and indiscriminate distribution of 2-DG have hampered its application. Although nanocarriers can facilitate targeted delivery to improve drug bioavailability, they often suffer from undesirable drug loading and potential toxicity caused by carrier materials. Thus, carrier-free nanodrugs formed by pure therapeutic drugs with satisfying biological activity might possess promising potential for RA therapy. Herein, we reported the carrier-free nanodrug self-assembled from 2-DG and Curcumin (Cur) without any other ingredient. Cur is a natural anti-inflammatory agent and has been widely investigated for inflammatory diseases therapy. The self-assembly of 2-DG/Cur nanodrug (2-DCNP) does not require any additional material. Therefore, the application of 2-DCNP can avoid the potential side effects caused by carrier materials. Inflammatory cells usually exhibited high expression of glucose transporter protein 1 (GLUT1) to facilitate glucose utilization. Thus, 2-DCNP with 2-DG on the surface might promote selective drug delivery to inflamed joints due to the high affinity between 2-DG and GLUT1. Our results indicated that 2-DCNP treatment could effectively inhibit glycolysis level to finally achieve desirable therapeutic efficacy in arthritic rats. This carrier-free nanodrug aiming at regulating glucose metabolism in inflamed joints might provide new insight for RA therapy.

Topics: Animals; Arthritis, Rheumatoid; Curcumin; Glucose; Glucose Transporter Type 1; Inflammation; Nanoparticles; Rats

Arsenic (As) as a neurotoxic environmental pollutant has attracted extensive attention. Curcumin (Cur) is a natural antioxidant that shows an excellent protective effect against arsenic trioxide (ATO)-induced toxicity in many animal organs. However, the mechanism of Cur against ATO-induced hypothalamic toxicity in ducks has not yet been fully elucidated. Here, ducks were treated with ATO and/or Cur during 28 days; the results showed that ATO exposure induced growth retardation, messy feathers, and abnormal posture in ducks. Moreover, ATO caused neuron vacuolar degeneration and disintegration in the hypothalamus of ducks. Simultaneously, ATO induced blood-brain barrier damage, downregulated the expression of ZO-1, Occludin, and mediated NF-κB activation, resulting in an increase in inflammatory factors (TLR-4, NF-κB, TNF-α, IL-2, and IL-6). Furthermore, ATO increased the production of pyroptosis-related factors (Caspase-1, IL-18, IL-1), exacerbating the inflammatory damage through NLRP3-mediated inflammasome activation. Cur, on the other hand, exerted excellent inhibitory effects on inflammation and pyroptosis. In summary, our study revealed that ATO triggered inflammation and pyroptosis by modulating NF-κB/NLRP3 signaling pathways in the hypothalamus of ducks, and Cur can alleviate inflammation and pyroptosis caused by ATO. Therefore, as a plant extract, Cur has the potential to prevent and cure ATO-induced hypothalamus toxicity.

Topics: Animals; Arsenic Trioxide; Curcumin; Ducks; Inflammation; NF-kappa B; NLR Family, Pyrin Domain-Containing 3 Protein; Pyroptosis; Signal Transduction

Lipopolysaccharides (LPS) are the main pathogenic substances in Gram-negative bacteria. The aim of this study was to investigate the preventive effects of dietary curcumin (CUR) on LPS toxicity in the duck ileum. The duck diet was supplemented with CUR (0.5 g kg. LPS significantly decreased the ileal villus-to-crypt ratio in the non-supplemented CUR group. Dietary CUR alleviated LPS-induced morphological damage to the ileum. Moreover, dietary CUR alleviated oxidative stress by increasing the levels of total superoxide dismutase (T-SOD) (P < 0.05) and glutathione S-transferase (GST) (P < 0.05) and decreasing the production of malonic dialdehyde (MDA) (P < 0.05) in control ducks and LPS-challenged ducks. Dietary CUR significantly inhibited the LPS-induced massive production of inflammatory factors (IL-1β, IL-6, and TNF-α) (P < 0.05). CUR induced the inhibition of TLR4 and activation of Nrf2 to reduce the expression of inflammation-related genes (TLR4, NF-κB, IKK, TXNIP, NLRP3, caspase-1, IL-1β, IL-6, and TNF-α). Moreover, dietary CUR ameliorated the decrease in claudin-1 and occludin expression (P < 0.05) and improved ZO-1 expression in the duck ileum (P < 0.05).. In conclusion, dietary CUR has beneficial effects on LPS-induced ileal damage, oxidative damage, and inflammatory response by inhibiting the TLR/NF-κB and activating the Nrf2 signaling pathways in ducks. This study provides valuable information regarding the therapeutic uses of CUR in duck ileitis. © 2022 Society of Chemical Industry.

Topics: Animals; Curcumin; Ducks; Ileitis; Inflammation; Interleukin-6; Lipopolysaccharides; NF-E2-Related Factor 2; NF-kappa B; Oxidative Stress; Toll-Like Receptor 4; Tumor Necrosis Factor-alpha

Inflammation-related diseases are recognized as the major cause of morbidity around the globe. In this study, the anti-inflammatory potential of sericin, curcumin, and their mixture was investigated in vivo and in vitro. Edema was induced via 1% carrageenan and then sericin (0.03, 0.06, 0.09 mg/ml), curcumin (1%, 2%, 3%), and their mixture doses were applied topically. The paw circumference and thickness were measured after 1-, 2-, 3-, 4-, 5-, and 6-hour post-carrageenan injection. The levels of IL-4 and IL-10 were measured from the serum. In mice fibroblast cells, sericin (20, 40, 60 μg/ml), curcumin (5, 10, 20 μM), and mixture concentrations were applied and then stimulated with lipopolysaccharide (LPS). Afterward, the cells were used for the analysis of gene expression, and the supernatant was collected for protein expression of IL-1β, IL-4, and IL-10. Our results demonstrated that sericin and curcumin caused a dose-dependent reduction in edema, whereas the mixture-treated group reduced the paw thickness and circumference most significantly (p = .0001). Furthermore, the mixture treatment of carrageenan-inflicted group increased the levels of anti-inflammatory cytokines, IL-4 (650.87 pg/ml) and IL-10 (183.14 pg/ml), in comparison to the carrageenan control. The in vitro data revealed that among all the treatment doses, the mixture-treated group has effectively reduced the gene (1.13-fold) and protein (51.9 pg/ml) expression of IL-1β in comparison to McCoy cells stimulated with LPS. Moreover, mixture treatment elevated the expression of IL-4 and IL-10 at genes (4.3-fold and 3.7-fold, respectively) and protein levels (169.33 and 141.83 pg/ml, respectively). The current study reports the enhanced anti-inflammatory effects of the mixture of curcumin and sericin through modulating expressions of interleukins in vitro and in vivo. Thus, natural products (curcumin and sericin)-based formulations have greater potential for clinical investigations.

Topics: Animals; Anti-Inflammatory Agents; Burns; Carrageenan; Curcumin; Edema; Inflammation; Interleukin-10; Interleukin-4; Lipopolysaccharides; Mice; Sericins

Our study aimed to elucidate the correlation of macrophage (mø) with the inflammatory reaction in ulcerative colitis (UC) and the influence of curcumin (Cur) on mø chemotaxis in mice with UC.. A total of 49 patients with UC (research group; RG) admitted between June 2020 and October 2021 and 56 healthy individuals (control group; CG) who visited concurrently were selected as the study participants. The peripheral blood mononuclear cells (PBMCs) were analyzed, and M1-type/M2-type mø and inflammatory factors (IFs) interleukin (IL)-1, IL-6, IL-10, tumor necrosis factor alpha (TNF-α) and transforming growth factor beta (TGF-β) were detected. In addition, 15 BALB/c mice were purchased and divided into the normal group fed normally, the UC model group established with sodium dextran sulfate (DSS) and the Cur group induced by DSS + Cur feeding. Colon tissue mø was collected from mice to measure mø activity via CCK-8 and to quantify levels of IFs and chemokine CCL2 by polymer chain reaction (PCR)c and Western blotting.. The RG had a higher percentage of peripheral blood M1-type mø and a lower percentage of M2-type mø and M1/M2 mø ratio than the CG (P < .05). In the RG, IL-1, IL-6 and TNF-α all increased and were inversely correlated with the ratio of M1/M2 mø, while IL-10 and TGF-β decreased, with a positive connection with the M1/M2 mø ratio. In the UC model mice, mø activity increased, but the apoptosis rate decreased. mø activity was lower in the Cur group than in the model and normal groups; mø apoptosis in the Cur group was higher than in the model group but lower than in the normal group. In addition, proIFs increased and anti-IFs decreased in the model group, and Cur also ameliorated this process. Finally, CCL2 and MCP-1 levels in the model group were also increased, while those in the Cur group were lower compared with the model group.. In UC, the M1/M2 mø ratio is severely misadjusted, activation of M1-type mø is enhanced and pro-IFs are released in large quantities. Cur can ameliorate the abnormal activation of mø in mice with UC, inhibit mø chemotaxis and alleviate the inflammatory reaction, which may make it a new option for UC treatment in the future.

Topics: Animals; Chemotaxis; Colitis, Ulcerative; Curcumin; Disease Models, Animal; Inflammation; Interleukin-10; Interleukin-6; Leukocytes, Mononuclear; Macrophages; Mice; Transforming Growth Factor beta; Tumor Necrosis Factor-alpha

Background Transplantation of extracellular vesicles (EVs) from stem cells is a feasible scheme for traumatic spinal cord injury (SCI). However, there is no relevant report about stem cells derived EVs loaded with curcumin for SCI treatment. Methods Mouse umbilical cord mesenchymal stem cells (MUMSCs) were incubated in the medium containing curcumin (20 µM) for 48 h. Extracellular vesicles (EVs) and curcumin-primed EVs (Cur-EVs) were collected by ultracentrifugation. Characterizations of EVs/Cur-EVs were analyzed by western blotting with CD9 and CD81 antibodies, transmission electron microscopy and nano-tracking analysis. Curcumin in the Cur-EVs was analyzed by high performance liquid phase chromatography at 430 nm wavelength. Immunofluorescence and in vivo imaging methods were used to confirm biocompatibility of EVs/Cur-EVs in vitro and in vivo. Mice with complete SCI were treated with EVs/Cur-EVs to compare the differences of locomotor function, inflammation, histological changes and remyelination. Results The isolated EVs and Cur-EVs from MUMSCs have good biocompatibility. Compared with the model mice, the locomotor function, inflammation and axonal regeneration of mice were significantly improved after injection of Cur-EVs/EVs. Furthermore, it is more effective for structural and functional recovery of complete SCI after the Cur-EVs treatment compared with the EVs treatment. In the lesioned regions, the macrophage polarization from M1 to M2 phenotype and axonal regeneration were significantly improved in the Cur-EVs group compared with the EVs group. Conclusions Our data suggested that EVs from MUMSCs might be a promising drug delivery vehicle of curcumin for the efficient and biocompatible treatment of severe SCI.

Topics: Animals; Curcumin; Extracellular Vesicles; Inflammation; Mesenchymal Stem Cells; Mice; Rats; Rats, Sprague-Dawley; Spinal Cord; Spinal Cord Injuries; Umbilical Cord

Hepatic ischemia-reperfusion injury (IRI) is a common innate immune-mediated sterile inflammatory response in liver transplantation and liver tumor resection. Neutrophil extracellular traps (NETs) can aggravate liver injury and activates innate immune response in the process of liver IRI. However, Curcumin (Cur) can reverse this damage and reduce NETs formation. Nevertheless, the specific regulatory mechanism is still unclear in liver IRI. This study aimed to explore the potential mechanisms that how does Cur alleviate hepatic IRI by inhibits NETs production and develop novel treatment regimens.. We established a hepatic IRI model by subjecting C57BL/6J mice to 60 min of ischemia, followed by reperfusion for 2 h, 6 h, 12 h, and 24 h respectively. Subsequently, we were separated into 5 groups, namely the I/R group, Cur group, DNase-1 group, Cur + DNase1 group and sham operation group. Serum alanine aminotransferase (ALT) and aspartate transaminase (AST), Hematoxylin-eosin staining, immunofluorescence, and TUNEL analysis were applied to assess liver injury degree and NETs levels. Western blot assay was used to detect the protein levels of apoptosis-related proteins and MEK pathway proteins.. Cur could alleviate hepatic IRI by inhibiting the generation of NETs via suppressing the MEK/ERK pathway. In addition, this study also revealed that DNase-1 is vital for alleviating hepatic IRI by reducing the generation of NETs.. Cur combined with DNase-1 was more effective than the two drugs administered alone in alleviating hepatic IRI by inhibiting the generation of NETs. These results also suggested that curcumin combined with DNase-1 was a potential therapeutic strategy to mitigate hepatic IRI.

Topics: Animals; Curcumin; Deoxyribonucleases; Extracellular Traps; Inflammation; Liver; Mice; Mice, Inbred C57BL; Mitogen-Activated Protein Kinase Kinases; Reperfusion Injury

The occurrence of osteoarthritis (OA) is highly correlated with the reduction of joint lubrication performance, in which persistent excessive inflammation and irreversible destruction of cartilage dominate the mechanism. The inadequate response to monotherapy methods, suboptimal efficacy caused by undesirable bioavailability, short retention, and lack of stimulus-responsiveness, are few unresolved issues. Herein, we report a pH-responsive metal-organic framework (MOF), namely, MIL-101-NH

Topics: Basic Helix-Loop-Helix Transcription Factors; Chondrocytes; Curcumin; Humans; Hydrogen-Ion Concentration; Inflammation; Metal-Organic Frameworks; Osteoarthritis; RNA, Small Interfering

Adhesion band formation is a common cause of morbidity for patients undergoing surgeries. Anti-inflammatory and anti-fibrotic properties of curcumin, a pharmacologically active component of Curcuma longa, have been investigated in several studies. The aim of this study is to explore the therapeutic potential of curcumin in attenuating post-operative adhesion band (PSAB) formation in both peritoneal and peritendinous surgeries in animal models.. Bio-mechanical, histological and quantitative evaluation of inflammation, and total fibrosis scores were graded and measured in the presence and absence of phytosomal curcumin.. Results showed that phytosomal curcumin significantly decreased severity, length, density and tolerance of mobility of peritendinous adhesions as well as incidence and severity of abdominal fibrotic bands post-surgery. Curcumin may decrease inflammation by attenuating recruitment of inflammatory cells and regulating oxidant/anti-oxidant balance in post-operative tissue samples. Moreover, markedly lower fibrosis scores were obtained in the adhesive tissues of phytosomal curcumin-treated groups which correlated with a significant decrease in quantity, quality and grading of fibers, and collagen deposition in animal models.. These results suggest that protective effects of phytosomal curcumin against PSAB formation is partially mediated by decreasing inflammation and fibrosis at site of surgery. Further studies are needed to investigate the therapeutic potential of this molecule in preventing PSAB.

Topics: Animals; Curcumin; Inflammation; Models, Animal; Tissue Adhesions

The direct effects of particulate matter (PM) on lung injury and its specific molecular mechanisms are unclear. However, experimental evidence has shown that oxidative stress-mediated inflammation in macrophages is the main pathological outcome of PM exposure. Curcumin has been reported to protect organs against the disturbance of homeostasis caused by various toxic agents through anti-inflammatory and antioxidative effects. However, the protective action of curcumin against PM-induced pulmonary inflammation and the underlying mechanism have not been thoroughly investigated. In this study, we established a PM-induced pulmonary inflammation mouse model using the intratracheal instillation method to investigate the protective ability of curcumin against PM-induced pulmonary inflammation. Compared to the mice treated with PM only, the curcumin-treated mice showed alleviated alveolar damage, decreased immune cell infiltration, and reduced proinflammatory cytokine production in both lung tissue and BALF. To evaluate the underlying mechanism, the mouse macrophage cell line RAW264.7 was used. Pretreatment with curcumin prevented the production of PM-induced proinflammatory cytokines by deactivating NF-κB through the suppression of MAPK signaling pathways. Furthermore, curcumin appears to attenuate PM-induced oxidative stress through the activation of Nrf2 and downstream antioxidant signaling. Our findings demonstrate that curcumin protects against PM-induced lung injury by suppressing oxidative stress and inflammatory activation in macrophages.

Topics: Animals; Antioxidants; Curcumin; Inflammation; Lung Injury; Macrophages; Mice; NF-E2-Related Factor 2; NF-kappa B; Oxidative Stress; Particulate Matter; Pneumonia

Mutations in cartilage oligomeric matrix protein (COMP) causes protein misfolding and accumulation in chondrocytes that compromises skeletal growth and joint health in pseudoachondroplasia (PSACH), a severe dwarfing condition. Using the MT-COMP mice, a murine model of PSACH, we showed that pathological autophagy blockage was key to the intracellular accumulation of mutant-COMP. Autophagy is blocked by elevated mTORC1 signaling, preventing ER clearance and ensuring chondrocyte death. We demonstrated that resveratrol reduces the growth plate pathology by relieving the autophagy blockage allowing the ER clearance of mutant-COMP, which partially rescues limb length. To expand potential PSACH treatment options, CurQ+, a uniquely absorbable formulation of curcumin, was tested in MT-COMP mice at doses of 82.3 (1X) and 164.6 mg/kg (2X). CurQ+ treatment of MT-COMP mice from 1 to 4 weeks postnatally decreased mutant COMP intracellular retention, inflammation, restoring both autophagy and chondrocyte proliferation. CurQ+ reduction of cellular stress in growth plate chondrocytes dramatically reduced chondrocyte death, normalized femur length at 2X 164.6 mg/kg and recovered 60% of lost limb growth at 1X 82.3 mg/kg. These results indicate that CurQ+ is a potential therapy for COMPopathy-associated lost limb growth, joint degeneration, and other conditions involving persistent inflammation, oxidative stress, and a block of autophagy.

Topics: Achondroplasia; Animals; Cartilage Oligomeric Matrix Protein; Chondrocytes; Curcumin; Disease Models, Animal; Extracellular Matrix Proteins; Growth Plate; Inflammation; Matrilin Proteins; Mice; Mutation

Myocardial infarction contributes to the development of cardiovascular disease, and leads to severe inflammation and health hazards. Our previous studies identified C66, a novel curcumin analogue, had pharmacological benefits in suppressing tissue inflammation. Therefore, the present study hypothesized C66 might improve cardiac function and attenuate structural remodeling after acute myocardial infarction. Administration of 5 mg/kg C66 for 4-week significantly improved cardiac function and decreased infarct size after myocardial infarction. C66 also effectively reduced cardiac pathological hypertrophy and fibrosis in non-infarct area. In vitro H9C2 cardiomyocytes, C66 also exerted the pharmacological benefits of anti-inflammatory and anti-apoptosis under hypoxic conditions Mechanistically, C66 inhibited cardiac inflammation and cardiomyocyte apoptosis by targeting on JNK phosphorylation, whereas replenishment of JNK activation abolished the cardioprotective benefits of C66 treatment. Taken together, curcumin analogue C66 inhibited the activation of JNK signaling, and possessed pharmacological benefits in alleviating myocardial infarction-induced cardiac dysfunction and pathological tissue injuries.

Topics: Animals; Curcumin; Inflammation; MAP Kinase Kinase 4; Mice; Myocardial Infarction; Myocytes, Cardiac

Ulcerative Colitis (UC) is a disease that negatively affects quality of life and is associated with sustained oxidative stress, inflammation and intestinal permeability. Vitamin D and Curcumin; It has pharmacological properties beneficial to health, including antioxidant and anti-inflammatory properties. Our study investigates the role of Vitamin D and Curcumin in acetic acid-induced acute colitis model. To investigate the effect of Vitamin D and Curcumin, Wistar-albino rats were given 0.4 mcg/kg Vitamin D (Post-Vit D, Pre-Vit D) and 200 mg/kg Curcumin (Post-Cur, Pre-Cur) for 7 days and acetic acid was injected into all rats except the control group. Our results; colon tissue TNF-α, IL-1β, IL-6, IFN-γ and MPO levels were found significantly higher and Occludin levels were found significantly lower in the colitis group compared to the control group (

Topics: Acetic Acid; Animals; Anti-Inflammatory Agents; Antioxidants; Colitis; Colitis, Ulcerative; Colon; Curcumin; Inflammation; Interleukin-6; Occludin; Quality of Life; Rats; Rats, Wistar; Tumor Necrosis Factor-alpha; Vitamin D

This study aimed to investigate the effect of intranasal treatment of gold nanoparticles (GNPs) and Curcumin (Cur) on the lipopolysaccharide (LPS)-induced acute pulmonary inflammatory response. A single intraperitoneal injection of LPS (0.5 mg/Kg) was performed, and the animals in the Sham group were injected with 0.9% saline. Treatment was daily intranasally with GNPs (2.5 mg/L), Cur (10 mg/kg) and GNP-Cur started 12 h after LPS administration and ended on the seventh day. The results show that the treatment performed with GNP-Cur was the most effective to attenuate the action of pro-inflammatory cytokines, and a lower leukocyte count in the bronchoalveolar lavage, in addition to positively regulating anti-inflammatory cytokines in relation to other groups. As a result, it promoted an oxirreductive balanced environment in the lung tissue, providing a histological outcome with a reduction in inflammatory cells and greater alveolar area. The group treated with GNPs-Cur was superior to the other groups, with better anti-inflammatory activity and reduced oxidative stress, resulting in less morphological damage to lung tissue. In conclusion, the use of reduced GNPs with curcumin demonstrates promising effects in the control of the acute inflammatory response, helping to protect the lung tissue at the biochemical and morphological levels.

Topics: Animals; Anti-Inflammatory Agents; Curcumin; Cytokines; Gold; Inflammation; Lipopolysaccharides; Lung; Metal Nanoparticles; Pneumonia; Rats; Rats, Wistar

Topics: Animals; Curcuma; Curcumin; Hypoglycemic Agents; Inflammation; Oxidative Stress; Paraquat; Pioglitazone; PPAR gamma; Rats

Mesenchymal stem cells (MSCs) derived exosomes (MSCs/Exo) is considered a new strategy in cell free regenerative therapy. Curcumin preconditioning of MSCs reported to improve the anti- inflammatory and immunomodulatory properties of MSCs. We investigated the efficacy of exosome (Exo) obtained from curcumin-preconditioned MSCs (MSCs/Exo-Cur) vs. MSC/Exo without curcumin to ameliorate and prevent recurrence of non-alcoholic fatty liver (NASH) disease.. In-vivo, methionine/choline-deficient diet (MCD) induced mice non-alcoholic fatty liver disease (NASH) were injected with MSCs/Exo without curcumin or MSCs/Exo-Cur with curcumin. We found that mice treated with MSCs/Exo-Cur had significantly ameliorated steatosis, inflammation, as evaluated by the reduced fibrosis in histopathological examination, decreased the serum level of liver enzymes (p < 0.001), liver triglycerides (TG) (p < 0.001) and cholesterol (Ch) (p < 0.001) and increased the lipid peroxidation (p < 0.001) compared to MSCs/Exo-treated mice. These effects remained for 3 months after treatment in MSCs/Exo-Cur-treated mice while features of NASH returned in MSCs/Exo-treated group. In vitro, HepG2 cells were cultured with palmitic acid (PA) and treated with MSCs/Exo or MSCs/Exo-Cur: the MSCs/Exo-Cur exposure reversed the lipotoxic effect from 4.5 to 1.7 fold vs 4.0 fold in MSCs/Exo and oxidative stress in PA-treated HepG2 cells (p < 0.001). We found that MSCs/Exo-Cur regulated the key markers of inflammatory and oxidative stress, genes responsible for fibrogenesis of the liver, key genes of lipid synthesis and transport. Interestingly, MSCs/Exo-Cur significantly down regulated the ASK-JNK-BAX genes involved in mitochondrial stress and apoptosis compared to MSCs/Exo (p < 0.001).. Our study indicated that exosomes derived from curcumin preconditioned MSCs were able to ameliorate and protect against recurrence of NASH and regulated inflammatory, oxidative stress and mitochondrial-dependent apoptosis ASK-JNK-BAX genes.

Topics: Animals; bcl-2-Associated X Protein; Curcumin; Exosomes; Fatty Liver, Alcoholic; Inflammation; Mesenchymal Stem Cells; Mice; Non-alcoholic Fatty Liver Disease; Oxidative Stress

Acute pancreatitis (AP) is a pathology characterized by activated digestive enzymes to digest pancreatic tissue and inflammation. This study aimed to investigate the effect of curcumin, which has antioxidant and anti-inflammatory properties, on AP and its effectiveness at different doses.. Forty Sprague Dawley albino male rats, 12 weeks old, weighing 285-320 g, were used in the study. The rats were divided into control, curcumin, AP, low (100 mg/kg), and high (200mg/kg) dose curcumin groups. An experimental pancreatitis model was created with 5 g/kg L-arginine and samples (amylase, lipase, IL-1β, IL-6, TNF-alpha, CRP, histopathological) were taken after 72 hours.. There was no difference between the groups in terms of the weight of the rats (p=0.76). In the AP group, it was observed that the experimental pancreatitis model was successfully created after examination. Laboratory and histopathological examination results in the curcumin-administered groups were regressed compared to the AP group. The decrease in laboratory values was higher in the high-dose curcumin group than in the low-dose (p<0.001).. Laboratory and histopathological changes occur in AP according to clinical severity. The antioxidant and anti-inflammatory effects of curcumin are known. In the light of this information and according to the results of our study, it has been shown that curcumin is effective in the treatment of AP, and the effect of curcumin increases with the dose increase. Curcumin is effective in treating AP. However, while high-dose curcumin was more effective in inflammatory response than low-dose, it showed similar histopathological results.. Acute, Curcumin, Cytokines, Inflammation, Pancreatitis.. La pancreatite acuta (AP) è una patologia caratterizzata dall’attivazione di enzimi digestivi pancreatici in grado di determinare la digestione del tessuto pancreatico e l’infiammazione. Questo studio era finalizzato a studiare l’effetto della curcumina, che ha proprietà antiossidanti e antinfiammatorie, sull’AP e la sua efficacia a diverse dosi. Nello studio sperimentale sono stati utilizzati quaranta ratti maschi albini Sprague Dawley, di 12 settimane di età, del peso di 285-320 g. I ratti sono stati divisi in cinque gruppi: 1) di controllo; 2) trattati con curcumina; 3) grupp AP (pancreatite acuta) provocata sperimentalmente; 4) AP, trattata con curcumina a basso dosaggio (100 mg/kg); 5) AP trattata con curcumina ad alto dosaggio (200 mg/kg). È stato creato un modello sperimentale di pancreatite con 5 g/kg di L-arginina e sono stati prelevati campioni (amilasi, lipasi, IL-1β, IL- 6, TNF-alfa, CRP, istopatologico) dopo 72 ore. RISULTATI: Non c’era differenza tra i gruppi in termini di peso dei ratti (p=0,76). Nel gruppo 3 (AP), è stato osservato dopo l’esame che il modello sperimentale di pancreatite era stato creato con successo. I risultati degli esami di laboratorio e istopatologici nei gruppi trattati con curcumina sono risultati regrediti rispetto a quelli del gruppo AP. La diminuzione dei valori di laboratorio è stata maggiore nel gruppo trattato con curcumina ad alto dosaggio rispetto a quello a basso dosaggio (p<0,001). CONCLUSIONE: Cmbiamenti dei dati di laboratorio e quelli istopatologici si verificano in AP in base alla gravità clinica. Sono noti gli effetti antiossidanti e antinfiammatori della curcumina. Alla luce di queste informazioni e in base ai risultati del nostro studio, è stato dimostrato che la curcumina è efficace nel trattamento dell’AP e l’effetto della curcumina aumenta con l’aumento della dose. La curcumina è efficace nel trattamento dell’AP. Tuttavia, sebbene la curcumina ad alte dosi fosse più efficace nella risposta infiammatoria rispetto a quelle a basse dosi, ha mostrato risultati istopatologici simili.

Topics: Acute Disease; Animals; Anti-Inflammatory Agents; Antioxidants; Arginine; Curcumin; Disease Models, Animal; Inflammation; Pancreas; Pancreatitis; Rats; Rats, Sprague-Dawley

This study was conducted to assess the mitigating effects of curcumin (Cur) on immunotoxicity in the spleen of broilers induced by the polybrominated diphenyl ether BDE-209. Eighty one-day-old broilers were allocated to the following four groups: control group, BDE-209 (0.4 g/kg) group, BDE-209 (0.4 g/kg) + Cur (0.3 mg/kg) group, and Cur (0.3 mg/kg) group. Growth performance, immunological function, inflammation, and apoptosis were assessed after 42 days of treatment. The findings demonstrate that firstly, Cur restored spleen damage caused by BDE-209 by increasing body weight, decreasing feed-to-gain ratio, correcting the spleen index, and improving the histopathological structure of the spleen. Secondly, Cur relieved BDE-209-induced immunosuppression by increasing the levels of the immunoglobulins IgG, IgM, and IgA in the serum, as well as the levels of white blood cells and lymphocytes. The levels at which GATA binding protein 3, T-box expressed in T cells, interferon-γ, and interleukin (IL)- 4 are expressed were controlled. The ratio of T helper (Th) type 1 (Th1) to Th2 cells in the spleen of broilers was also controlled. Thirdly, Cur reduced the expression of Toll like receptor (TLR) 2, TLR4, nuclear factor (NF)-κB, IL-8, IL-6, and IL-1β, which alleviated BDE-209-induced inflammation in broilers. Cur reduced BDE-209-induced apoptosis by increasing the expression of the bcl-2 protein, decreasing the expression of cleaved caspase-3 and bax proteins, decreasing the bax/bcl-2 protein ratio, and decreasing the mean optical density of TUNEL. These results suggest that Cur protects broiler spleens from BDE-209-induced immunotoxicity via modulating humoral immunity, the equilibrium between Th1 and Th2 cells, the TLRs/NF-κB inflammatory pathway, and the apoptotic pathway.

Topics: Animals; Apoptosis; bcl-2-Associated X Protein; Chickens; Curcumin; Halogenated Diphenyl Ethers; Immunity; Inflammation; NF-kappa B; Spleen

Cyclooxygenase (COX) and Lipoxygenase (LOX) are essential enzymes for arachidonic acid (AA) to eicosanoids conversion. These AA-derived eicosanoids are essential for initiating immunological responses, causing inflammation, and resolving inflammation. Dual COX/5-LOX inhibitors are believed to be promising novel anti-inflammatory agents. They inhibit the synthesis of prostaglandins (PGs) and leukotrienes (LTs), but have no effect on lipoxin formation. This mechanism of combined inhibition circumvents certain limitations for selective COX-2 inhibitors and spares the gastrointestinal mucosa. Natural products, i.e. spice chemicals and herbs, offer an excellent opportunity for drug discovery. They have proven anti-inflammatory properties. However, the potential of a molecule to be a lead/ drug candidate can be much more enhanced if it has the property of inhibition in a dual mechanism. Synergistic activity is always a better option than the molecule's normal biological activity. Herein, we have explored the dual COX/5-LOX inhibition property of the three major potent phytoconsituents (curcumin, capsaicin, and gingerol) from Indian spices using in silico tools and biophysical techniques in a quest to identify their probable inhibitory role as anti-inflammatory agents. Results revealed the dual COX/5-LOX inhibitory potential of curcumin. Gingerol and capsaicin also revealed favorable results as dual COX/5-LOX inhibitors. Our results are substantiated by target similarity studies, molecular docking, molecular dynamics, energy calculations, DFT, and QSAR studies. In experimental inhibitory (in vitro) studies, curcumin exhibited the best dual inhibitory activities against COX-1/2 and 5-LOX enzymes. Capsaicin and gingerol also showed inhibitory potential against both COX and LOX enzymes. In view of the anti-inflammatory potential these spice chemicals, this research could pave the way for more scientific exploration in this area for drug discovery.

Topics: Anti-Inflammatory Agents; Arachidonate 5-Lipoxygenase; Capsaicin; Curcumin; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Humans; Inflammation; Lipoxygenase; Lipoxygenase Inhibitors; Molecular Docking Simulation; Spices

Curcumin, a diketone compound extracted from turmeric's rhizome, is an effective anti-inflammatory drug with multiple pharmacological activities. However, its low oral bioavailability due to its low water solubility and permeability severely limits its clinical applications. Therefore, to enhance the oral bioavailability of curcumin, further enhance its anti-inflammatory effects, and improve its potential in the treatment of airway inflammation, a curcumin nanocrystalline self-stabilizing Pickering emulsion (Cur-NSSPE) was prepared through high-pressure homogenization. Next, Cur-NSSPE was dried using a freeze-drying method to produce Cur-NSSPE-FDP. The prepared Cur-NSSPE and Cur-NSSPE-FDP were physically characterized. The release behavior and transmembrane transport capability of Cur-NSSPE-FDP in vitro were evaluated. Pharmacokinetic study was performed to evaluate its oral bioavailability. The anti-inflammatory effects of Cur-NSSPE-FDP in vivo and in vitro were investigated using RAW 264.7 macrophage inflammation model induced by LPS and IFN-γ and asthma model in BALB/c mice induced by OVA. The average particle size of Cur-NSSPE was (163.66 ± 6.78) nm, and the average drug content was (2.78 ± 0.01) mg/mL. The transmission electron microscopy results showed that the droplets were spherical in shape with a relatively uniform size, and the curcumin nanocrystals formed a spherical core-shell structure wrapped at the interface of the droplets. The scanning electron microscopy showed that Cur-NSSPE-FDP was a neatly arranged, having loose and porous network structure. Furthermore, it can significantly improve the cumulative release of curcumin in vitro and improve oral bioavailability in rats, increase the uptake of RAW264.7 and Caco-2 cells, promote the transport of curcumin across Caco-2 cells, significantly inhibit the expression of inflammatory factors NO, IL-6, TNF-a, MDA, IgE and ICAM-1, and improve the expression of IL-10 and SOD. These results indicated that the curcumin nanocrystalline self-stabilizing Pickering emulsion-freeze dried powder improved the oral bioavailability of curcumin and enhanced its therapeutic effect in airway inflammation.

Topics: Animals; Biological Availability; Caco-2 Cells; Curcumin; Emulsions; Humans; Inflammation; Mice; Nanoparticles; Particle Size; Powders; Rats

Previous studies has shown that nucleotide-binding and oligomerization domain-containing protein 2 (NOD2) is expressed in Fibroblast-like synoviocytes (FLSs) of rheumatoid arthritis (RA) patients which is stimulated by muramyl dipeptide (MDP) present in the joint environment and induces inflammation via the NF-κB pathway. Also, other studies have shown that curcumin inhibits proliferation, migration, invasion, and Inflammation and on the other hand increases the apoptosis of RA FLSs. In this study, we aim to evaluate the effect of curcumin, a natural anti-inflammatory micronutrient, on the expression of NOD2 and inflammatory cytokines.. Synovial membranes were collected from ten patients diagnosed with RA and ten individuals with traumatic injuries scheduled for knee surgery. The FLSs were isolated and treated with 40 μM curcumin alone or in combination with 20.3 μM MDP for 24 h. mRNA was extracted, and real-time PCR was performed to quantitatively measure gene expression levels of NOD2, p65, IL-6, TNF-α, and IL-1β.. The study findings indicate that administering MDP alone can significantly increase the mRNA expression levels of IL-6 and IL-1β in the trauma group and TNF-α in the RA group. Conversely, administering curcumin alone or in combination whit MDP can significantly reduce mRNA expression levels of P65 and IL-6 in FLSs of both groups. Moreover, in FLSs of RA patients, a single curcumin treatment leads to a significant reduction in NOD2 gene expression.. This study provides preliminary in vitro evidence of the potential benefits of curcumin as a nutritional supplement for RA patients. Despite the limitations of the study being an investigation of the FLSs of RA patients, the results demonstrate that curcumin has an anti-inflammatory effect on NOD2 and NF-κB genes. These findings suggest that curcumin could be a promising approach to relieve symptoms of RA.

Topics: Anti-Inflammatory Agents; Arthritis, Rheumatoid; Curcumin; Cytokines; Fibroblasts; Humans; Inflammation; Interleukin-6; NF-kappa B; Nod2 Signaling Adaptor Protein; RNA, Messenger; Synoviocytes; Tumor Necrosis Factor-alpha

The versatile nature of macrophages and their ability to switch between various activation states plays a pivotal role in both promoting and inhibiting inflammatory processes. In pathological inflammatory conditions, classically activated M1 macrophages are often associated with initiating and maintaining inflammation, while alternatively activated M2 macrophages are linked to the resolution of chronic inflammation. Achieving a favorable equilibrium between M1 and M2 macrophages is crucial for mitigating inflammatory environments in pathological conditions. Polyphenols are known to have strong inherent antioxidative capabilities, and curcumin has been found to reduce macrophage inflammatory reactions. However, its therapeutic efficacy is compromised due to its poor bioavailability. The present study aims to harness the properties of curcumin by loading it in nanoliposomes and enhancing the M1-to-M2 macrophage polarization. A stable liposome formulation was achieved at 122.1

Topics: Curcumin; Cytokines; Humans; Inflammation; Macrophages; Phenotype

The microenvironment of excessive inflammation and the activation of apoptotic signals are primary barriers to neurological recovery following spinal cord injury (SCI). Thus, long-lasting anti-inflammation has become an effective strategy to navigate SCI. Herein, a curcumin (CUR)-containing nanosystem (FCTHPC) with high drug loading efficiency was reported via assembling hydrophobic CUR into cross-linked polyphosphazene (PPZ), and simultaneous loading and coordinating with porous bimetallic polymers for greatly enhanced the water-solubility and biocompatibility of CUR. The nanosystem is noncytotoxic when directing its biological activities. By inhibiting the expression of pro-inflammatory factors (IL-1β, TNF-α and IL-6) and apoptotic proteins (C-caspase-3 and Bax/Bcl-2), which may be accomplished by activating the Wnt/β-catenin pathway, the versatile FCTHPC can significantly alleviate the damage to tissues and cells caused by inflammation and apoptosis in the early stage of SCI. In addition, the long-term in vivo studies had demonstrated that FCTHPC could effectively inhibit the formation of glial scars, and simultaneously promote nerve regeneration and myelination, leading to significant recovery of spinal cord function. This study emphasises the promise of the biocompatible CUR-based nanosystem and provides a fresh approach to effectively treat SCI.

Topics: Animals; Anti-Inflammatory Agents; Apoptosis; Curcumin; Inflammation; Nanoparticles; Nerve Regeneration; Polymers; Rats; Rats, Sprague-Dawley; Spinal Cord; Spinal Cord Injuries

Exposure to fine particulate matter with a diameter ≤2.5 μm (PM

Topics: Acute Lung Injury; Curcumin; Humans; Inflammation; Nanoparticles; Particulate Matter; Reactive Oxygen Species; Serum Albumin, Bovine; Silicon Dioxide

Intraocular inflammation seriously impairs vision, and the effectiveness of intraocular drug delivery is hampered by various physiological barriers, such as the corneal barrier. In this paper, we present a simple approach to fabricating a dissolvable hybrid microneedles (MNs) patch for the efficient delivery of curcumin to treat intraocular inflammatory disorders. Water-insoluble curcumin was first encapsulated into polymeric micelles with high anti-inflammatory capacities, and then were combined with hyaluronic acid (HA) to create a dissolvable hybrid MNs patch using a simple micromolding method. Curcumin was amorphously dispersed within the MNs patch as indicated by Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), and X-ray diffraction (XRD) analyses. According to an in vitro drug release study, the proposed MNs patch provided sustainable drug release over 8 h. Following its in vivo topical application, the MNs patch demonstrated an extended pre-corneal retention time over 3.5 h and exhibited great ocular biocompatibility. Additionally, such MNs patch could reversibly penetrate the corneal epithelium, generating an array of microchannels on the corneal surface, thereby increasing ocular bioavailability. Of greater significance, the use of MNs patch demonstrated the improved therapeutic effectiveness in treating endotoxin-induced uveitis (EIU) in a rabbit model compared to curcumin eye drops via a significant reduction in the infiltration of inflammatory cells such as CD45

Topics: Animals; Cornea; Curcumin; Drug Delivery Systems; Inflammation; Needles; Rabbits; Uveitis

Benign prostatic hyperplasia (BPH) is a progressive urological disease occurring in middle-aged and elderly men, which can be characterized by the non-malignant overgrowth of stromal and epithelial cells in the transition zone of the prostate. Previous studies have demonstrated that lycopene can inhibit proliferation, while curcumin can strongly inhibit inflammation. This study aims to determine the inhibitory effect of the combination of lycopene and curcumin on BPH.. To induce BPH models in vitro and in vivo, the BPH-1 cell line and Sprague Dawley (SD) rats were used, respectively. Rats were divided into six groups and treated daily with a vehicle, lycopene (12.5 mg/kg), curcumin (2.4 mg/kg), a combination of lycopene and curcumin (12.5 mg/kg + 2.4 mg/kg) or finasteride (5 mg/kg). Histologic sections were examined via hematoxylin and eosin (H&E) staining and immunohistochemistry. Hormone and inflammatory indicators were detected via ELISA. Network pharmacology analysis was used to fully predict the therapeutic mechanism of the combination of lycopene and curcumin on BPH.. Combination treatment significantly attenuated prostate hyperplasia, alleviated BPH pathological features and decreased the expression of Ki-67 in rats. The upregulation of the expression of testosterone, dihydrotestosterone (DHT), 5α-reductase, estradiol (E2) and prostate-specific antigen (PSA) in BPH rats was significantly blocked by the combination treatment. The expression levels of inflammatory factors including interleukin (IL)-1β, IL-6 and tumor necrosis factor (TNF)-α were strongly inhibited by the combination treatment. From the network pharmacology analysis, it was found that the main targets for inhibiting BPH are AKT1, TNF, EGFR, STAT3 and PTGS2, which are enriched in pathways in cancer.. The lycopene and curcumin combination is a potential and more effective agent to prevent or treat BPH.

Topics: Animals; Cell Proliferation; Curcumin; Humans; Inflammation; Lycopene; Male; Plant Extracts; Propionates; Prostatic Hyperplasia; Rats; Rats, Sprague-Dawley; Testosterone; Testosterone Propionate

Cadmium chloride (Cd) and sodium arsenite (As) are two prominent examples of non-biodegradable substances that accumulate in ecosystems, pose a serious risk to human health and are not biodegradable. Although the toxicity caused by individual use of Cd and As is known, the toxicity of combined use (Cd+As) to mammals is poorly understood. The present study aims to investigate the hepatoprotective effect of curcumin (CUR), a naturally occurring bioactive component isolated from the root stem of Curcuma longa Linn., in preventing liver damage caused by a Cd+As mixture. A group of 30 Sprague-Dawley rats were subjected to intraperitoneal administration of Cd+As (0.44 mg/kg+5.55 mg/kg i.p.) and CUR (100 or 200 mg/kg) for a period of 14 days. The experimental results showed that the animals treated with Cd+As exhibited changes in liver biochemical parameters, inflammation and oxidative stress at the end of the experiment. Administration of CUR significantly reduced inflammation, oxidative stress and lipid peroxidation in the Cd+As plus CUR groups compared to the Cd+As group. Furthermore, histological examination of the liver tissue showed that administration of CUR had led to a significant reduction in the liver damage observed in the Cd+As group. The present study provides scientific evidence for the protective effects of CUR against lipid peroxidation, inflammation, oxidative stress and liver damage induced by Cd+As in the liver of rats. The results of our in vivo experiments were confirmed by those of our molecular modelling studies, which showed that CUR can enhance the diminished antioxidant capacity caused by Cd+As.

Topics: Animals; Antioxidants; Arsenic; Cadmium; Curcumin; Ecosystem; Humans; Inflammation; Interleukin-1beta; Liver; Liver Diseases; Mammals; NF-kappa B; Oxidative Stress; Rats; Rats, Sprague-Dawley

An excessive inflammatory response induced by cytokine storms is the primary reason for the deterioration of patients with acute lung injury (ALI). Though natural polyphenols such as curcumin (CUR) have anti-inflammation activity for ALI treatment, they often have limited efficacy due to their poor solubility in water and oxidising tendency. This study investigates a highly cross-linked polyphosphazene nano-drug (PHCH) developed by copolymerisation of CUR and acid-sensitive units (4-hydroxy-benzoic acid (4-hydroxy-benzylidene)-hydrazide, D-HBD) with hexachlorotripolyphosphonitrile (HCCP) for improved treatment of ALI. PHCH can prolong the blood circulation time and targeted delivery into lung inflammation sites by enhancing CUR's water dispersion and anti-oxidant properties. PHCH also demonstrates the inflammation-responsive release of CUR in an inflammation environment due to the acid-responsive degradation of hydrazine bonds and triphosphonitrile rings in PHCH. Therefore, PHCH has a substantial anti-inflammation activity for ALI treatment by synergistically improving CUR's water-solubility, bioavailability and biocompatibility. As expected, PHCH attenuates the cytokine storm syndrome and alleviates inflammation in the infected cells and tissues by down-regulating several critical inflammatory cytokines (TNF-α, IL-1β, and IL-8). PHCH also decreases the expression of p-p65 and C-Caspase-1, inhibiting NLRP3 inflammasomes and suppressing NF-κB signalling pathways. The administrated mice experiments confirmed that PHCH accumulation was enhanced in lung tissue and showed the efficient scavenging ability of reactive oxygen species (ROS), effectively blocking the cytokine storm and alleviating inflammatory damage in ALI. This smart polyphosphazene nano-drug with targeting delivery property and inflammation-responsive release of curcumin has excellent potential for the clinical treatment of various inflammatory diseases, including ALI.

Topics: Acute Lung Injury; Animals; Anti-Inflammatory Agents; Curcumin; Cytokine Release Syndrome; Inflammation; Lipopolysaccharides; Lung; Mice; Nanoparticles; NF-kappa B

This study aims to investigate the potential therapeutic effect of exosomes derived from macrophages loaded with curcumin (Exos-cur) on the healing of diabetic wounds. As a new type of biomaterial, Exos-cur has better stability, anti-inflammation, and antioxidation biological activity. In in vitro experiments, Exos-cur can promote the proliferation, migration, and angiogenesis of HUVECs (human umbilical vein endothelial cells) while reducing the ROS (reactive oxygen species) produced by HUVECs induced by high glucose, regulating the mitochondrial membrane potential, reducing cell oxidative damage, and inhibiting oxidative stress and inflammation. In the in vivo experiment, the Exos-cur treatment group had an increased percentage of wound closure and contraction compared with the diabetic wound control group. Hematoxylin-eosin staining (HE) and Masson staining showed that the Exos-cur treatment group had more advanced re-epithelialization, and the generated mature granulation tissue was rich in a large number of capillaries and newly deposited collagen fibers. Western blot and immunofluorescence analyses showed that Exos-cur can inhibit inflammation by activating the Nrf2/ARE pathway, upregulate the expression of wound healing-related molecules, promote angiogenesis, and accelerate wound healing in diabetic rats. These results show that Exos-cur has a good therapeutic effect on diabetic skin defects and provide experimental evidence for the potential clinical benefits of Exos-cur.

Topics: Animals; Curcumin; Diabetes Mellitus, Experimental; Exosomes; Human Umbilical Vein Endothelial Cells; Humans; Inflammation; Macrophages; Rats; Wound Healing

Curcumin has antioxidant properties resulting from its radical scavenging ability and inhibition of inflammation-associated factors. However, its lack of solubility, instability, and poor bioavailability are impediments to its therapeutic use. As potential alternatives, we synthesized and performed chemical analysis of thirty diarylidene-N-methyl-4-piperidone (DANMP), diheteroarylidene-N-methyl-4-piperidone (DHANMP), and spirobibenzopyran (SBP) derivatives, one of which was also characterized by single crystal X-ray diffraction. All compounds were evaluated for antioxidant activity via 2,2-Diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay and for drug-like properties in silico. A subset of five compounds was investigated in terms of aqueous solubilities, which were significantly improved compared to that of curcumin. In vitro assessments of cellular and anti-inflammatory effects were conducted via real time polymerase chain reaction (RT-PCR) and Griess assays to evaluate the presence of inflammatory/activated (M1) markers and production of nitric oxide (NO) species, which are associated with inflammation. The five compounds reduced levels of markers and NO to extents similar to or better than curcumin in inflamed cells, and showed no adverse effects on cell viability. We show that these compounds possess anti-inflammatory properties and may be used as curcumin-substitutes with improved characteristics.

Topics: Anti-Inflammatory Agents; Antioxidants; Curcumin; Humans; Inflammation; Nitric Oxide; Piperidones

The formation of an inhibitory inflammatory microenvironment after spinal cord injury (SCI) remains a great challenge for nerve regeneration. The poor local microenvironment exacerbates nerve cell death; therefore, the reconstruction of a favorable microenvironment through small-molecule drugs is a promising strategy for promoting nerve regeneration.. In the present study, we synthesized curcumin-loaded micelle nanoparticles (Cur-NPs) to increase curcumin bioavailability and analyzed the physical and chemical properties of Cur-NPs by characterization experiments. We established an in vivo SCI model in rats and examined the ability of hind limb motor recovery using Basso-Beattie-Bresnahan scoring and hind limb trajectory assays. We also analyzed neural regeneration after SCI using immunofluorescence staining.. The nanoparticles achieved the intelligent responsive release of curcumin while improving curcumin bioavailability. Most importantly, the released curcumin attenuated local inflammation by modulating the polarization of macrophages from an M1 pro-inflammatory phenotype to an M2 anti-inflammatory phenotype. M2-type macrophages can promote cell differentiation, proliferation, matrix secretion, and reorganization by secreting or expressing pro-repair cytokines to reduce the inflammatory response. The enhanced inflammatory microenvironment supported neuronal regeneration, nerve remyelination, and reduced scar formation. These effects facilitated functional repair in rats, mainly in the form of improved hindlimb movements.. Here, we synthesized pH/temperature dual-sensitive Cur-NPs. While improving the bioavailability of the drug, they were also able to achieve a smart responsive release in the inflammatory microenvironment that develops after SCI. The Cur-NPs promoted the regeneration and functional recovery of nerves after SCI through anti-inflammatory effects, providing a promising strategy for the repair of SCIs.

Topics: Animals; Anti-Inflammatory Agents; Curcumin; Hydrogen-Ion Concentration; Inflammation; Micelles; Nanoparticles; Rats; Rats, Sprague-Dawley; Spinal Cord Injuries; Temperature

Due to oral nano-delivery systems for the treatment of inflammatory bowel disease (IBD) are often failed to accumulated to the colonic site and could not achieve controlled drug release, it's urgent to develop a microenvironment responsive drug delivery to improve therapy efficacy. Inflammation at the IBD site is mainly mediated by macrophages, which are the key effector cells. Excessive inflammation leads to oxidative stress and intestinal mucosal damage. The use of curcumin (CUR) and emodin (EMO) together for the treatment of IBD is promising due to their respective anti-inflammatory and intestinal mucosal repair effects. In view of the pH gradient environment of gastrointestinal tract, here we prepared pH-responsive sodium alginate (SA) hydrogel-coated nanoemulsions to co-deliver CUR and EMO (CUR/EMO NE@SA) to achieve controlled drug release and specifically target macrophages of the colon.. In this study, a pH-responsive CUR/EMO NE@SA was successfully developed, in which the CUR/EMO NE was loaded by chitosan and further crosslinked with sodium alginate. CUR/EMO NE@SA had a pH-responsive property and could achieve controlled drug release in the colon. The preparation could significantly alleviate and improve the colon inflammatory microenvironment by decreasing TNF-α and IL-6 expression, increasing IL-10 expression, scavenging reactive oxygen species in macrophages, and by ameliorating the restoration of intestinal mucosal tight junction protein expression. Furthermore, we revealed the molecular mechanism of the preparation for IBD treatment, which might due to the CUR and EMO synergic inhibition of NF-κB to improve the pro-inflammatory microenvironment. Our study provides a new IBD therapy strategy via synergically inhibiting inflammatory, repairing mucosal and clearing ROS by pH-sensitive hydrogel-encapsulated nanoemulsion drug delivery system, which might be developed for other chronic inflammatory disease treatment.. It's suggested that pH-sensitive hydrogel-coated nanoemulsion-based codelivery systems are a promising combinatorial platform in IBD.

Topics: Alginates; Anti-Inflammatory Agents; Curcumin; Emodin; Humans; Hydrogels; Inflammation; Inflammatory Bowel Diseases; Intestinal Mucosa

Traumatic heterotopic ossification (THO) represents one of the most prominent contributors to post-traumatic joint dysfunction, which currently lacks an effective and definitive preventative approach. Inflammatory activation due to immune dyshomeostasis during the early stages of trauma is believed to be critical in initiating the THO disease process. This study proposes a dual-homeostatic modulation (DHM) strategy to synergistically prevent THO without compromising normal trauma repair by maintaining immune homeostasis and inducing stem cell homeostasis. A methacrylate-hyaluronic acid-based hydrogel spray device encapsulating a curcumin-loaded zeolitic imidazolate framework-8@ceric oxide (ZIF-8@CeO2, CZC) nanoparticles (CZCH) is designed. Photo-crosslinked CZCH is used to form hydrogel films fleetly in periosteal soft tissues to achieve sustained curcumin and CeO2 nanoparticles release in response to acidity and reactive oxygen species (ROS) in the inflammatory microenvironment. In vitro experiments and RNA-seq results demonstrated that CZCH achieved dual-homeostatic regulation of inflammatory macrophages and stem cells through immune repolarization and enhanced efferocytosis, maintaining immune cell homeostasis and normal differentiation. These findings of the DHM strategy are also validated by establishing THO mice and rat models. In conclusion, the CZCH hydrogel spray developed based on the DHM strategy enables synergistic THO prevention, providing a reference for a standard procedure of clinical operations.

Topics: Animals; Curcumin; Hydrogels; Inflammation; Mice; Ossification, Heterotopic; Rats; Wound Healing

As a polyphenolic compound originated from the food spice turmeric, curcumin (CUR) has various pharmacological effects, such as anti-inflammatory, antioxidation, antiproliferative, and antiangiogenic activities. Psoriasis is centered on the overproduction of Th1- and Th2-related cytokines (e.g., interleukin [IL]-23, IL-17, TNF-α, IL-22), which is involved in the occurrence and development of its pathogenesis. However, whether CUR is involved in the treatment of psoriasis and its specific mechanisms are not fully understood.. In this study, we detected the therapeutic effect of CUR (100 mg/kg/day) on IMQ-induced dermatitis in mice, analyzed by PASI scores, ELISA, HE staining, immunofluorescence. Moreover, we further confirmed the alteration in the relative abundance of the gut microbiota through 16sRNA to explore whether CUR could regulate the gut microbiota of IMQ-induced mice.. Through intragastric administration, CUR can alleviate psoriasis-like lesions of mice by decreasing PASI scores, reducing the level of IL-6, IL-17A, IL-22, IL-23, TNF-α, and TGF-β1, promoting the expression of IL-10. Moreover, 16sRNA sequencing revealed that CUR could regulate the alteration in the abundance alteration of gut microbiota related to inflammation, such as Alistipes, Mucispirillum, and Rikenella at genus level. The correlation analysis further confirmed the close association between important microflora and psoriasis-like inflammation indicators.. CUR exerts the effect of alleviating dermatitis of psoriatic mice by regulating Th-17 related inflammatory factors. Moreover, the changes in gut microbiota via CUR may be another factor of relieving IMQ-induced lesions in mice. Therefore, CUR may be a highly promising candidate for the treatment of psoriasis.

Topics: Animals; Curcumin; Dermatitis; Gastrointestinal Microbiome; Imiquimod; Inflammation; Interleukin-23; Mice; Tumor Necrosis Factor-alpha

Transplantation of curcumin-activated olfactory ensheathing cells (aOECs) improved functional recovery in spinal cord injury (SCI) rats. Nevertheless, little is known considering the underlying mechanisms. At the present study, we investigated the promotion of regeneration and functional recovery after transplantation of aOECs into rats with SCI and the possible underlying molecular mechanisms. Primary OECs were prepared from the olfactory bulb of rats, followed by treatment with 1µM CCM at 7-10 days of culture, resulting in cell activation. Concomitantly, rat SCI model was developed to evaluate the effects of transplantation of aOECs in vivo. Subsequently, microglia were isolated, stimulated with 100 ng/mL lipopolysaccharide (LPS) for 24 h to polarize to M1 phenotype and treated by aOECs conditional medium (aOECs-CM) and OECs conditional medium (OECs-CM), respectively. Changes in the expression of pro-inflammatory and anti-inflammatory phenotypic markers expression were detected using western blotting and immunofluorescence staining, respectively. Finally, a series of molecular biological experiments including knock-down of triggering receptor expressed on myeloid cells 2 (TREM2) and analysis of the level of apolipoprotein E (APOE) expression were performed to investigate the underlying mechanism of involvement of CCM-activated OECs in modulating microglia polarization, leading to neural regeneration and function recovery. CCM-activated OECs effectively attenuated deleterious inflammation by regulating microglia polarization from the pro-inflammatory (M1) to anti-inflammatory (M2) phenotype in SCI rats and facilitated functional recovery after SCI. In addition, microglial polarization to M2 elicited by aOECs-CM in LPS-induced microglia was effectively reversed when TREM2 expression was downregulated. More importantly, the in vitro findings indicated that aOECs-CM potentiating LPS-induced microglial polarization to M2 was partially mediated by the TREM2/nuclear factor kappa beta (NF-κB) signaling pathway. Besides, the expression of APOE significantly increased in CCM-treated OECs. CCM-activated OECs could alleviate inflammation after SCI by switching microglial polarization from M1 to M2, which was likely mediated by the APOE/TREM2/NF-κB pathway, and thus ameliorated neurological function. Therefore, the present finding is of paramount significance to enrich the understanding of underlying molecular mechanism of aOECs-based therapy and provide a novel the

Topics: Animals; Anti-Inflammatory Agents; Apolipoproteins E; Curcumin; Inflammation; Lipopolysaccharides; Microglia; NF-kappa B; Olfactory Mucosa; Rats; Recovery of Function; Signal Transduction; Spinal Cord; Spinal Cord Injuries

Multiple sclerosis (MS) is an autoimmune central nervous system (CNS) disorder indicated by demyelination, chronic inflammation, and neuronal destruction. Regional demyelination, inflammation responses, scar development, and various axonal damage are pathological characteristics of MS. Curcumin is a hydrophobic polyphenol extracted from the rhizome of the turmeric plant. In addition to anti-inflammatory effects, beneficial therapeutic effects such as antioxidant, anti-cancer and nerve protection have also been seen from this compound. The purpose of the current investigation was to provide light on the potential benefits of Curcumin in treating experimental autoimmune encephalomyelitis (EAE), the animal model of MS.. in Female C57BL/6 mice were used to induce EAE through myelin oligodendroglial glycoprotein (MOG). Curcumin doses of 100 and 200 mg/kg were administered orally in the treatment groups starting on the first day of EAE induction. Brains and splenocytes were extracted from euthanized animals on day 25 following EAE induction. Demyelination and leukocyte infiltration, proliferation, cytokine, and gene expression profiles were assessed. Our findings demonstrate that both low and high doses of Curcumin decreased the progression of EAE. Histological analyses revealed low infiltration of leukocytes into the CNS. Curcumin therapy enhanced Th2 and Treg cell secretion of IL-4, IL-10, and TGF-β although considerably decreasing IFN-γ and TNF-α. Curcumin-induced Th2 and Treg cell cytokine production and transcription factor gene expression (IL-13, GATA3, STAT6 and IL-35, CTLA4, Foxp3) and anti-inflammatory cytokines (IL-27, IL-33).. Overall, these findings provide additional evidence that Curcumin can slow disease development and alleviate symptoms in EAE through stimulating Treg and Th2 cell polarization. They support Curcumin's potential therapeutic role in MS.

Topics: Animals; Anti-Inflammatory Agents; Curcumin; Cytokines; Encephalomyelitis, Autoimmune, Experimental; Immunity; Inflammation; Mice; Mice, Inbred C57BL; Multiple Sclerosis; Patient Acuity; Spices

Ulcerative colitis (UC) faces some barriers in oral therapy, such as how to safely deliver drugs to the colon and accumulate in the colon lesions. Hence, we report an advanced yeast particles system loaded with supramolecular nanoparticles with ROS scavenger (curcumin) to treat UC by reducing oxidative stress state and inflammatory response and accelerating the reprogramming of macrophages. In this study, the dual-sensitive materials are bonded on β-cyclodextrin (β-CD), the D-mannose (Man) is modified to adamantane (ADA), and then loaded with curcumin (CUR), to form a functional supramolecular nano-delivery system (Man-CUR NPs) through the host-guest interaction. To improve gastrointestinal stability and colonic accumulation of Man-CUR NPs, yeast cell wall microparticles (YPs) encapsulated Man-CUR NPs to form Man-CUR NYPs via electrostatic adsorption and vacuum extrusion technologies. As expected, the YPs showed the strong stability in complex gastrointestinal environment. In addition, the Man modified supramolecular nanoparticles demonstrated excellent targeting ability to macrophages in the in vitro cellular uptake study and the pH/ROS sensitive effect of Man-CUR NPs was confirmed by the pH/ROS-dual stimulation evaluation. They also enhanced lipopolysaccharide (LPS)-induced inflammatory model in macrophages through downregulation of pro-inflammatory factors, upregulation of anti-inflammatory factors, M2 macrophage polarization, and scavenging the excess ROS. Notably, in DSS-induced mice colitis model, Man-CUR NYPs can reduce the inflammatory responses by modulating TLR4/NF-κB signaling pathways, alleviate oxidative stress by Nrf2/HO-1 signaling pathway, promote macrophages reprogramming and improve the favorable recovery of the damaged colonic tissue. Taken together, this study not only provides strategy for "supramolecular curcumin nanoparticles with pH/ROS sensitive and multistage therapeutic effects" in "advanced yeast particles", but also provided strong theoretical support multi-effect therapy for UC.

Topics: Animals; Colitis, Ulcerative; Curcumin; Disease Models, Animal; Inflammation; Mice; Reactive Oxygen Species; Saccharomyces cerevisiae

COVID-19, an acute respiratory syndrome caused by the SARS-CoV-2 virus, was first reported in late 2019 in Wuhan, China, and rapidly escalated into a global pandemic. The condition can lead to organ dysfunction and ultimately death through its onset of acute respiratory distress syndrome (ARDS). Disease severity has been linked to proinflammatory cytokines which activate the NF-κB and STAT transcription factors in infected cells. It has been proven that lncRNAs play a very important role in reducing or increasing inflammatory factors. This makes them potentially valuable in recognizing pathogenesis pathways and therapeutic targets in COVID-19. Nanocurcumin is known as an antioxidant, tumor suppressor and anti-inflammatory substance, and it can be effective to reduce inflammation caused by the disease of COVID-19. This study analyzed Sequence Read Archive data from COVID-19 patients with acute versus milder symptoms, identifying dysregulated genes and non-coding RNAs. To verify this correlation, the expression of the candidate gene was evaluated with quantitative polymerase chain reaction (qPCR) in mouse models, while immunoglobulin (Ig) G titer was measured using enzyme-linked immunosorbent assay (ELISA) in mouse serum samples. Here we introduced a novel lncRNA called HSD17B3-AS1, suggested as a therapeutic target in COVID-19 patients with acute symptoms. Furthermore, we revealed nanocurcumin is reducing the expression of HSD17B3-AS1 which leads to reduced inflammation in mice. These results suggest that HSD17B3-AS1 plays a significant regulatory role in managing COVID-19, and the downregulation of HSD17B3-AS1 by Nanocurcumin presents a promising treatment option for minimizing complications in COVID-19 patients.

Topics: Animals; Antioxidants; COVID-19; Curcumin; Humans; Immunoglobulin G; Inflammation; Mice; RNA, Long Noncoding; SARS-CoV-2

Cisplatin dose-dependent nephrotoxicity is a major issue limiting its proper use in cancer treatment. Inflammation, redox imbalance, and dysregulated cell death are the most plausible underlying pathomechanics. Curcumin and the glucagon-like peptide-1 receptor agonist, liraglutide, have been investigated in various experimental models for their antioxidant, anti-inflammatory, and cell death modulatory effects. Hence, this work was designed to investigate curcumin and liraglutide nephroprotective effects and how they behave together against cisplatin-induced acute kidney injury (AKI) in an experimental Wistar rat model. The study comprised 61 rats divided randomly into 6 unequal groups: control I and II, cisplatin-induced nephrotoxicity, curcumin-treated, liraglutide-treated, and co-treated groups. Renal index, serum nephrotoxicity markers (Cr, BUN, NGAL), renal glycogen synthase kinase-3 β (GSK-3β), oxidant/antioxidant parameters (MDA, MPO, GSH, NQO1, HO-1), and inflammatory biomolecules (TNF-α, IL-1β) were assayed. Moreover, renal cleaved-caspase3 and the pyroptotic biomolecules (nod-like receptor family pyrin domain containing 3, gasdermin D N-terminal fragment) were immunoassayed. Furthermore, relative renal expression of both nuclear factor erythroid 2-related factor 2 (Nr-F2) and caspase1 was evaluated by qRT-PCR. Histopathological examination of renal tissue was carried out along with detection of Bcl-2 and Bax immunoreactivity. Cisplatin induced acute renal damage, augmented inflammation, dysregulated redox balance and induced apoptosis and pyroptosis. On the other hand, curcumin and liraglutide corrected the dysregulated mechanisms and normalized results to a great extent. Mutual use of curcumin and liraglutide exerted the greatest effect in the co-treatment group. Nr-F2/HO-1 axis and GSK-3β play a master role in their nephroprotective effect. In conclusion, curcumin and liraglutide have an ameliorative effect against cisplatin-induced nephrotoxicity and can be used alone or better in combination owing to their augmented effect launching promising avenues for cancer patients under cisplatin treatment, retarding AKI and enabling them to gain the best protocol effectiveness.

Topics: Acute Kidney Injury; Animals; Antioxidants; Apoptosis; Cisplatin; Curcumin; Glycogen Synthase Kinase 3 beta; Humans; Inflammation; Kidney; Liraglutide; Oxidative Stress; Pyroptosis; Rats; Rats, Wistar

Rheumatoid arthritis (RA) is an inflammatory disease. Curcumin can inhibit NF-κB and reduce the expression of inflammation-related genes.

Topics: Animals; Arthritis, Rheumatoid; Curcumin; Inflammation; Molecular Docking Simulation; NF-kappa B; Piperidones; Rats

Bronchoconstriction, along with inflammation and hyperresponsiveness is the characteristic feature associated with asthma, contributing to variable airflow obstruction, which manifests shortness of breath, cough and wheeze, etc. Histone deacetylases 8 (HDAC8) is the member of class I HDAC family and known to regulate microtubule integrity and muscle contraction. Therefore, we aimed to investigate the effects of HDAC8 inhibition in murine model of asthma using Pan-HDAC inhibitor curcumin (CUR) and HDAC8-specific inhibitor PCI-34051 (PCI), alone and in combination.. To develop asthmatic mouse model, Balb/c mice were sensitized and challenged with ovalbumin (OVA). CUR (10 mg/kg, pre, post, alone and combined treatment) and PCI (0.5 mg/kg), were administered through intranasal (i.n) route, an hour before OVA aerosol challenge. Effects of HDAC8 inhibition by CUR and PCI pretreatments were evaluated in terms of inflammation, oxidative stress and fibrosis markers. Efficacy of curcumin post-treatment (CUR(p)) was also evaluated simultaneously.. Inflammatory cell recruitment, oxidative stress (reactive oxygen species, nitric oxide), histamine and Immunoglobulin E (IgE) levels and expression of fibrosis markers including hydroxyproline, matrix metalloproteinases-9 and alpha smooth muscle actin (MMP-9 and α-SMA) were significantly reduced by CUR, CUR(p), PCI-alone and combined treatments. Protein expressions of HDAC8, Nuclear factor-κB (NF-κB) accompanied by MAPKs (mitogen-activated protein kinases) were significantly reduced by the treatments. Structural alterations were examined by histopathological analysis and linked with the fibrotic changes.. Present study indicates protective effects of HDAC8 inhibition in asthma using HDAC8 using CUR and PCI alone or in combination, attenuates airway inflammation, fibrosis and remodeling; hence, bronchoconstriction was accompanied through modulation of MAP kinase pathway.

Topics: Animals; Asthma; Curcumin; Disease Models, Animal; Fibrosis; Inflammation; Lung; Mice; Mice, Inbred BALB C; Mitogen-Activated Protein Kinases; Ovalbumin

Tumor-associated inflammation plays a vital role in cancer progression. Among the various stromal cells, cancer-associated fibroblasts are promising targets for cancer therapy. Several reports have indicated potent anti-inflammatory effects attributed to Curcumin. This study aimed to investigate whether inhibiting the inflammatory function of cancer-associated fibroblasts (CAFs) with Curcumin can restore anticancer immune responses. CAFs were isolated from breast cancer tissues, treated with Curcumin, and co-cultured with patients' PBMCs to evaluate gene expression and cytokine production alterations. Blood and breast tumor tissue samples were obtained from 12 breast cancer patients with stage II/III invasive ductal carcinoma. Fibroblast Activation Protein (FAP) + CAFs were extracted from tumor tissue, treated with 10 μM Curcumin, and co-cultured with corresponding PBMCs. The expression of smooth muscle actin-alpha (α-SMA), Cyclooxygenase-2(COX-2), production of PGE2, and immune cell cytokines were evaluated using Real-Time PCR and ELISA, respectively. Analyzes showed that treatment with Curcumin decreased the expression of genes α-SMA and COX-2 and the production of PGE2 in CAFs. In PBMCs co-cultured with Curcumin-treated CAFs, the expression of FoxP3 decreased along with the production of TGF-β, IL-10, and IL-4. An increase in IFN-γ production was observed that followed by increased T-bet expression. According to our results, Curcumin could reprogram the pro-tumor phenotype of CAFs and increase the anti-tumor phenotype in PBMCs. Thus, CAFs, as a component of the tumor microenvironment, are a suitable target for combination immunotherapies of breast cancer.

Topics: Breast Neoplasms; Cancer-Associated Fibroblasts; Cell Line, Tumor; Curcumin; Cyclooxygenase 2; Dinoprostone; Female; Fibroblasts; Humans; Inflammation; Tumor Microenvironment

Solid evidence has emerged supporting the role of nonextractable polyphenols (NEPs) and dietary fibers (DFs) as gut microbiota modulators. This study aims to elucidate gut microbiota-dependent release of turmeric NEPs and examine the possible anti-inflammatory mechanism in the dextran sulfate sodium-induced ulcerative colitis (UC) model. 1.5% DSS drinking water-induced C57BL/6J mice were fed a standard rodent chow supplemented with or without 8% extractable polyphenols (EPs), NEPs, or DFs for 37 days. The bound curcumin, demethoxycurcumin, and bisdemethoxycurcumin in NEPs were released up to 181.5 ± 10.6, 65.2 ± 6.0, and 69.5 ± 7.6 μg/mL by in vitro gut microbiota-simulated fermentation and released into the colon of NEP-supplemented mice by 5.7-, 11.0-, and 7.8-fold higher than pseudo germ-free mice, respectively (

Topics: Animals; Coleoptera; Colitis; Colitis, Ulcerative; Colon; Curcuma; Dextran Sulfate; Dietary Fiber; Disease Models, Animal; Gastrointestinal Microbiome; Inflammation; Mice; Mice, Inbred C57BL; Polyphenols

Chronic obstructive pulmonary disease (COPD) is a common respiratory disease characterized by symptoms of shortness of breath and chronic inflammation. Curcuma zedoaria (Christm.) Roscoe is a well-documented traditional medical herb that is frequently used in the treatment of COPD. Previously, we identified a diarylheptanoid compound (1-(4-hydroxy-5-methoxyphenyl)-7-(4,5-dihydroxyphenyl)-3,5-dihydroxyheptane; abbreviated as HMDD) from this herb that exhibited potent agonistic activity on β2-adrenergic receptors (β2 adrenoreceptor) that are present on airway smooth muscle cells. In this work, we used chemically synthesized HMDD compound, and confirmed its bioactivity on β2 adrenoreceptors. Then by a proteomics study and anti-inflammatory evaluation detections, we found that HMDD downregulated the nucleotide-binding oligomerization domain (NOD)-like receptor (NLR) signaling pathway and suppressed the NLRP3 receptor expression in RAW264.7 macrophages and in a COPD model in A549 lung carcinoma cells. HMDD also decreased nitric oxide production levels, and impacted other interleukins and the phosphorylation of NF-κB and ERK pathways. We performed molecular docking of HMDD on β2 adrenoreceptor and NLRP3 protein models. This work reports the anti-inflammatory effects of HMDD and suggests a dual-targeting mechanism of β2-adrenoreceptor agonism and NLRP3 inhibition. Such a mechanism scientifically supports the clinical uses of Curcuma zedoaria (Christm.) Roscoe in treating COPD, as it can simultaneously relieve persistent breathlessness and inflammation. HMDD can be considered as a potential non-steroidal anti-inflammatory drug in novel therapy design for the treatment of COPD and other inflammatory diseases.

Topics: Anti-Inflammatory Agents; Curcuma; Diarylheptanoids; Humans; Inflammation; Molecular Docking Simulation; NF-kappa B; NLR Family, Pyrin Domain-Containing 3 Protein; Pulmonary Disease, Chronic Obstructive; Signal Transduction

Achilles tendinopathy is a frequent pathological condition in adults with overused ankles, causing microtrauma, inducing tenocyte apoptosis and inflammatory response. Common treatment involves oral prescription or injection of anti-inflammatory agents, surgery, or shock-wave therapy. However, prolonged administration is not advisable due to adverse effects. Therefore, a novel and safe regimen is needed. Curcuma longa and Glycyrrhiza glabra extracts are known for their anti-inflammatory effects owing to their active compounds (curcumin and glycyrrhizin, respectively). This study aimed to determine the effect of combined extracts of Curcuma longa and Glycyrrhiza glabra on tendon healing in an animal model of Achilles tendinopathy (Wistar rats).. This study took place from February to May 2022 and compared the regimens administered to 32 animal models of Wistar rats with 4 healthy rats as a control group to determine the most effective therapeutic regimen: immobilization, immobilization with ibuprofen, or immobilization with the combined extract. The outcomes were measured to find which intervention provided the lowest inflammatory markers [High Mobility Group Box-1 (HMGB-1), Tumor Necrosis Factor-α (TNF-α), Chemokin motif ligand 12 (CXCL-12)], and improved tissue morphology represented by the BONAR score, decreased cross-sectional area (CSA), and increased Macrophage 2 (M2) differentiation.. After Achilles tendinopathy was induced, total immobilization (I1) was proven to be the most effective with the lowest CSA, whereas immobilization+175 mg/kg Curcuma longa+110 mg/kg Glycyrrhiza glabra extract (I5) was the most effective with the lowest HMGB-1 levels and the lowest CXCL-12 levels. Immobilization+131 mg/kg Curcuma longa+82.5 mg/kg Glycyrrhiza glabra extract (I6) was the most effective with the lowest Bonar score, while immobilization+87.5 mg/kg Curcuma longa+55 mg/kg Glycyrrhiza glabra extract (I7) was proven to be the most effective with the highest M2 coverage area and the lowest TNF-α levels.. We found that combined extract therapy was the most effective intervention for treating Achilles tendinopathy due to its ability to provide the lowest inflammatory markers.

Topics: Achilles Tendon; Animals; Curcuma; Glycyrrhiza; HMGB Proteins; Inflammation; Musculoskeletal Diseases; Plant Extracts; Rats; Rats, Wistar; Tendinopathy; Tumor Necrosis Factor-alpha

Asthma being an inflammatory disease of the airways lead to structural alterations in lungs which often results in the severity of the disease. Curcumin, diferuloylmethane, is well known for its medicinal properties but its anti-inflammatory potential via Histone deacetylase inhibition (HDACi) has not been revealed yet. Therefore, we have explored here, anti-inflammatory and anti-fibrotic potential of intranasal curcumin via HDAC inhibition and compared its potential with Sodium butyrate (SoB), a known histone deacetylase inhibitor of Class I and II series. Anti-inflammatory potential of SoB, has been investigated in cancer but not been studied in asthma before.. In present study, ovalbumin (OVA) was used to sensitize Balb/c mice and later exposed to (1%) OVA aerosol. Curcumin (5 mg/kg) and Sodium butyrate (50 mg/kg) was administered through intranasal route an hour before OVA aerosol challenge. Efficacies of SoB and Curcumin as HDAC inhibitors were evaluated in terms of different inflammatory parameters like, total inflammatory cell count, reactive oxygen species (ROS), histamine release, nitric oxide and serum IgE levels. Inflammatory cell recruitment was analyzed by H&E staining and structural alterations were revealed by Masson's Trichrome staining of lung sections.. Enhanced Matrix Metalloproteinase-2 and 9 (MMP-2 and MMP-9) activities were observed in bronchoalveolar lavage fluid (BALF) of asthmatic mice by gelatin zymography which was inhibited in both treatment groups. Protein expressions of MMP-9, HDAC 1, H3acK9 and NF-kB p65 were modulated in intranasal curcumin and SoB pretreatment groups.. This is the first report where intranasal curcumin inhibited asthma severity via affecting HDAC 1 (H3acK9) leading to NF-kB suppression in mouse model of allergic asthma.

Topics: Administration, Intranasal; Animals; Anti-Inflammatory Agents; Asthma; Bronchoalveolar Lavage Fluid; Butyric Acid; Curcumin; Disease Models, Animal; Fibrosis; Histone Deacetylase Inhibitors; Immunoglobulin E; Inflammation; Lung; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Mice; Mice, Inbred BALB C; Ovalbumin

The inflammation is tightly associated with tumor development, promoting or inhibiting tumorigenesis. And mutant p53 is speculated to promote inflammation and tumorigenesis. The tumor associated macrophages are usually educated to present the anti-inflammatory profile to tune down antitumor immunity. However, the impact of p53 mutants on macrophages is not clear. Here, we compared the basal inflammatory level and macrophage profiles in tumor cells and tumor samples with different p53 mutations. Data revealed that a lower inflammatory level was maintained in immune organs and tumor cells with p53 point mutations than those with p53 null mutation. Using the tumor cell-derived conditional media to culture macrophages, we found that the media from cells with p53 mutations, especially the point mutations, could decrease M1 markers and inhibit phagocytosis, suggesting the p53 mutation promoted M2 profile polarization. To target the p53 mutation induced M2 macrophage polarization, we applied low-concentration curcumin to the tumor cells with different p53 mutations. The data showed that curcumin could inhibit STAT3 signal and decrease PPARγ and CSF1 in tumor cells and tumor samples. In vitro, the co-culture assays showed that the curcumin treatment shifted p53 mutation educated macrophages back towards M1 profile. In vivo, the curcumin-treated MEFs showed obvious tumor inhibition, and the tumor samples displayed inhibited M2 markers. Results suggested that curcumin could inhibit p53 mutation educated macrophage induction and suppress M2-promoted tumorigenesis. Our study illustrated the inflammatory level under different p53 status and the inflammatory regulated role of curcumin in tumor environment. This study might provide a potential method in tumor personalized treatment aiming immune therapy in different p53 status.

Topics: Carcinogenesis; Curcumin; Humans; Inflammation; Mutation; Neoplasms; Tumor Microenvironment; Tumor Suppressor Protein p53

Curcumin and its analogues exhibited anti-inflammatory activity in different experimental models. Recently, we synthesized (2E,3E)-3-buten-2-one-4-(4-hydroxy-3-methoxyphenyl)-2-(4-(4-methoxyphenyl)-2-thiazolyl)hydrazone (RI75), a curcumin analogue with a thiazolyl hydrazone moiety. In the present study, we investigated the effects induced by RI75 in different models of inflammation and pain in mice, as well as some underlying mechanisms. Pre-treatment with RI75 (40 mg/kg, intraperitoneal; i.p.) or curcumin (40 mg/kg, i.p.) reduced the mechanical allodynia and paw edema induced by intraplantar (i.pl) injection of carrageenan. RI75 antiallodynic activity was reduced by pre-treatment with naltrexone (5 and 10 mg/kg, i.p.) and cyproheptadine (10 mg/kg, i.p.), but not glibenclamide (20 and 40 mg/kg, i.p.). In a model of neuropathic pain, a single i.p. administration of RI75 (40 mg/kg) or curcumin (40 mg/kg) attenuated the ongoing mechanical allodynia induced by repeated administrations of paclitaxel. Pre-treatment with RI75 (40 mg/kg, i.p.) or curcumin (40 mg/kg, i.p.) also reduced tumor necrosis factor-α and interleukin-6 production and myeloperoxidase activity induced by carrageenan. The results of the present study demonstrate that RI75, a synthetic curcumin analogue, exhibits antiallodynic and antiedematogenic activities. Activation of opioidergic and serotonergic mechanisms and reduced production of inflammatory mediators and neutrophil recruitment may underlie RI75 activities.

Topics: Animals; Curcumin; Disease Models, Animal; Edema; Hyperalgesia; Inflammation; Interleukin-6; Mice; Neuralgia; Tumor Necrosis Factor-alpha

The smart design of nanoparticles with varying surfaces may open a new avenue for potential biomedical applications. Consequently, several approaches have been established for controlled synthesis to develop the unique physicochemical properties of nanoparticles. However, many of the synthesis and functionalization methods are chemical-based and might be toxic to limit the full potential of nanoparticles. Here, curcumin (a plant-derived material) based synthesis of gold (Au) nanoparticles, followed by the development of a suitable exterior corona using isoniazid (INH, antibiotic), tyrosine (Tyr, amino acid), and quercetin (Qrc, antioxidant), is reported. All these nanoparticles (Cur-Au, Cur-Au

Topics: Animals; Curcumin; Gold; Inflammation; Metal Nanoparticles; Mice; Nanoparticles; Peroxidase; Peroxidases

Calebin A (CA) is one of the active constituents of turmeric and has anti-inflammatory and antioxidant effects. Excessive inflammation and cell apoptosis are the main causes of tendinitis and tendinopathies. However, the role of CA in tendinitis is still unclear and needs to be studied in detail. Tenocytes in monolayer or 3D-alginate cultures in the multicellular tendinitis microenvironment (fibroblast cells) with T-lymphocytes (TN-ME) or with TNF-α or TNF-β, were kept without treatment or treated with CA to study their range of actions in inflammation. We determined that CA blocked TNF-β-, similar to TNF-α-induced adhesiveness of T-lymphocytes to tenocytes. Moreover, immunofluorescence and immunoblotting showed that CA, similar to BMS-345541 (specific IKK-inhibitor), suppressed T-lymphocytes, or the TNF-α- or TNF-β-induced down-regulation of Collagen I, Tenomodulin, tenocyte-specific transcription factor (Scleraxis) and the up-regulation of NF-κB phosphorylation; thus, its translocation to the nucleus as well as various NF-κB-regulated proteins was implicated in inflammatory and degradative processes. Furthermore, CA significantly suppressed T-lymphocyte-induced signaling, similar to TNF-β-induced signaling, and NF-κB activation by inhibiting the phosphorylation and degradation of IκBα (an NF-κB inhibitor) and IκB-kinase activity. Finally, inflammatory TN-ME induced the functional linkage between NF-κB and Scleraxis, proposing that a synergistic interaction between the two transcription factors is required for the initiation of tendinitis, whereas CA strongly attenuated this linkage and subsequent inflammation. For the first time, we suggest that CA modulates TN-ME-promoted inflammation in tenocytes, at least in part, via NF-κB/Scleraxis signaling. Thus, CA seems to be a potential bioactive compound for the prevention and treatment of tendinitis.

Topics: Basic Helix-Loop-Helix Transcription Factors; Cinnamates; Curcumin; Humans; Inflammation; Jurkat Cells; Monoterpenes; NF-kappa B; Signal Transduction; Tendinopathy; Tenocytes

This work studies the capacity of curcumin to inhibit tumor necrosis alpha (TNFα)-induced inflammation, oxidative stress, and loss of intestinal barrier integrity, characterizing the underlying mechanisms.. The inhibition of NF-κB, ERK1/2, and JNK activation could be in part involved in the capacity of curcumin to mitigate intestinal inflammation, oxidant production, activation of redox-sensitive pathways, and prevention of monolayer permeabilization. These results support an action of dietary curcumin in sustaining gastrointestinal tract physiology.

Topics: Caco-2 Cells; Curcumin; Humans; Inflammation; MAP Kinase Signaling System; Mitogen-Activated Protein Kinase 3; Myosin Light Chains; NF-kappa B; Oxidants; Tumor Necrosis Factor-alpha

This study set out to assess the mitigative effects of curcumin on AFB1-induced necroptosis and inflammation in chicken liver. Ninety-six one-day-old AA broiler chickens were separated into four groups, including control group, AFB1 (1 mg/kg) group, curcumin (300 mg/kg) + AFB1 (1 mg/kg) group and curcumin (300 mg/kg) group. After 28 days treatment, livers were collected for different experimental analyses. The morphological observation results showed obvious necrotic characteristics, including cell swelling, rupture of cell and mitochondrial membranes and inflammation in chicken livers. AFB1 exposure increased oxidative stress index (ROS and MDA) and decreased the antioxidant activity markers (SOD, CAT and GSH) and ATPase activities in chickens' liver. ELISA results showed that AFB1 exposure significantly induced the cytokines (TNF-α, iNOS, IL-6 and IL-1β) release from the liver tissues. While, western blot and qRT-PCR results showed that the protein and mRNA expressions of inflammatory (TLR4/myd88/NF-κB) and necroptosis (RIPK1/RIPK3/MLKL) genes were up-regulated by AFB1 exposure. We suspect that signal crosstalk between TLR4 and TNF-α triggers inflammation and RIPK1/RIPK3 mediating necroptosis in AFB1-induced chicken liver injury. Curcumin can regulate the TLR4/RIPK signaling pathway, reduced oxidative stress biomarkers and inflammatory cytokines levels and attenuated the expression of necroptosis and inflammation genes altered by AFB1 to reduce necroptosis of chicken liver tissue. In conclusion, curcumin can protect against AFB1-induced necroptosis and inflammation by TLR4/RIPK pathway in chicken liver.

Topics: Aflatoxin B1; Animals; Chickens; Curcumin; Inflammation; Liver; Necroptosis; Toll-Like Receptor 4

Intra-uterine growth restriction (IUGR) is a serious, commonly occurring reproductive problem in humans. This study aimed to investigate the effects of daily curcumin supplementation during pregnancy on placental inflammation, in a rat model of IUGR. Pregnant rats were divided into three groups based on diet: (1) normal protein (19%) (NP), (2) low protein (8%) (LP), and (3) low protein + 100 mg curcumin/kg bw per day (LPC). The results showed that curcumin accumulation in the serum, placenta and liver. Fetal weight and placental total protein levels were increased in the LPC group compared with those in the LP group. Dietary curcumin supplementation normalized the low protein diet-induced decrease of placental weight, blood sinusoid area, and proliferating cell nuclear antigen (PCNA) protein expression levels. It also reversed the low protein diet-induced increase of serum triglyceride levels and tumor necrosis factor alpha-like (TNF-α), interleukin 1 beta (IL-1β), and interleukin 6 (IL-6) concentrations in both the placenta and serum. Additionally, it normalized the enhanced gene expression levels of the pro-inflammatory cytokines in the LP group to that in the NP group. Furthermore, it downregulated the inhibitor of kappa Balpha (IκBα) and nuclear factor kappa Balpha (NF-κB) phosphorylation. In conclusion, daily curcumin supplementation ameliorates placental inflammation in rats with IUGR by inhibiting the NF-κB signaling pathway.

Topics: Animals; Curcumin; Dietary Supplements; Female; Fetal Growth Retardation; Humans; Inflammation; NF-kappa B; Placenta; Pregnancy; Rats; Signal Transduction; Tumor Necrosis Factor-alpha

Tuberculosis (TB) is one of the ten leading causes of death worldwide. Patients with TB have been observed to suffer from depression and anxiety linked to social variables. Previous experiments found that the substantial pulmonary inflammation associated with TB causes neuroinflammation, neuronal death, and behavioral impairments in the absence of brain infection. Curcumin (CUR) is a natural product with antioxidant, anti-inflammatory and antibacterial activities. In this work, we evaluated the CUR effect on the growth control of mycobacteria in the lungs and the anti-inflammatory effect in the brain using a model of progressive pulmonary TB in BALB/c mice infected with drug-sensitive mycobacteria (strain H37Rv). The results have shown that CUR decreased lung bacilli load and pneumonia of infected animals. Finally, CUR significantly decreased neuroinflammation (expression of TNFα, IFNγ and IL12) and slightly increased the levels of nuclear factor erythroid 2-related to factor 2 (Nrf2) and the brain-derived neurotrophic factor (BDNF) levels, improving behavioral status. These results suggest that CUR has a bactericidal effect and can control pulmonary mycobacterial infection and reduce neuroinflammation. It seems that CUR has a promising potential as adjuvant therapy in TB treatment.

Topics: Animals; Anti-Inflammatory Agents; Antitubercular Agents; Brain; Brain-Derived Neurotrophic Factor; Curcumin; Disease Models, Animal; Inflammation; Lung; Male; Mice; Mice, Inbred BALB C; Mycobacterium tuberculosis; Tuberculosis; Tuberculosis, Pulmonary

The present study evaluated the antiparasitic effect of curcumin extract on Schistosoma mansoni in Swiss albino mice. The experimental design included four groups of S. mansoni - infected mice; without treatment (controls), curcumin-treated, Praziquantel (PZQ)-treated, and PZQ +curcumin treated mice. The results showed that curcumin improved ISHAK confluent necrosis score up to zero. PZQ +curcumin showed a significant reduction in portal inflammation. Both activity and fibrosis demonstrated lower scores in all treated groups, however, PZQ revealed a marked increase in confluent necrosis and interface hepatitis. Besides, the lobular inflammation revealed worsening in the overall ISHAK score in all treated groups compared with the control. Few periocular granulomas were recovered by PZQ +curcumin treatment at day 35 post-treatment (6±1.2), P-value <0.05. Curcumin revealed a mild reduction (60±7.376). Curcumin-treated groups, with and without PZQ, resulted in higher significant Immunoreactivity score (IRS) for Bcl-2-associated X (BAX) and lower Interleukine- 17A (IL-17A), and Human epidermal growth factor (EGF), compared to the control. However, PZQ revealed a lower mean IRS value in BAX, higher IL-17A and EGF in the periovulatory granuloma. It was concluded that PZQ +curcumin treatment had a potent synergistic outcome through lessening the number of granulomas, the inflammatory events, and the expression of EGF, and amelioration of apoptosis in the periovulatory granulomas if compared with either PZQ or curcumin alone.

Topics: Animals; Anthelmintics; bcl-2-Associated X Protein; Curcumin; Epidermal Growth Factor; Granuloma; Inflammation; Interleukin-17; Mice; Necrosis; Praziquantel; Schistosomiasis mansoni

Curcumin plays an important role in inflammation regulation. This study aimed to investigate the effect of curcumin on vascular smooth muscle cells (VSMCs) inflammation induced by lipopolysaccharide (LPS) and its mechanism. VSMCs were treated with different concentrations of curcumin (0, 50, 100 and 150 μg/mL). MTT assay and flow cytometry were used to analyze the effects of curcumin on LPS-induced VSMCs viability and apoptosis. The expression and release of inflammatory cytokines in VSMCs were detected by real-time quantitative polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA). Moreover, the proteins expressions of NF-κB and JNK signaling pathways were analyzed by western blot. Interestingly, the results showed that curcumin could reduce LPS induced inflammatory injury by increasing VSMC's viability, reducing apoptosis and inhibiting the release of inflammatory cytokines. In addition, curcumin increased the expression of Toll-like receptor 4 (TLR4) in LPS treated VSMCs. Mechanistically, we found that curcumin attenuated LPS-induced cell damage in VSMCs via inhibition of NF-κB and the JNK signal pathway. Curcumin can protect VSMCs from LPS induced inflammatory damage, which may be related to the blocking of NF-κB and the JNK signaling pathway. Herewith, curcumin could be potential therapeutics for the treatment of atherosclerosis.

Topics: Apoptosis; Curcumin; Humans; Inflammation; Lipopolysaccharides; MAP Kinase Signaling System; Muscle, Smooth, Vascular; NF-kappa B

Stress is a condition affecting different body systems. Curcumin (CUR) is a natural compound that has various pharmacological benefits. However, its poor oral bioavailability limits its therapeutic value. This study aimed to formulating curcumin loaded chitosan nanoparticles (CS.CUR.NPs) and investigate its gastroprotective and neuroprotective effects in rats subjected to cold restraint stress (CRS), in reference to conventional oral CUR preparation, and explore its underlying mechanism. Treated groups received either CUR or CS.CUR.NPs (100 mg∕kg) orally for 14 days before exposure to CRS. CRS elicited marked behavioral changes and gastric ulcer accompanied by histopathological abnormalities of the brain and stomach along with elevation of pain score. CUR and CS.CUR.NPs improved stress-induced gastric ulcer, cognitive performance, and pain sensation. Mechanistically, CRS disrupts oxidative and inflammatory status of the brain as manifested by high malondialdehyde and IL-6 and low total antioxidant capacity and IL-10, along with high C-reactive protein level. CRS decreased nuclear factor erythroid 2-related factor2 (Nrf2) and increased nuclear factor-kappa B (NF-κB) expressions. Furthermore, brain levels of unphosphorylated signal transducer and activator of transcription3 (U-STAT3) and glial fibrillary acidic protein (GFAP) were upregulated with stress. CUR and CS.CUR.NPs provided beneficial effects against harmful consequences resulting from stress with superior beneficial effects reported with CS.CUR.NPs. In conclusion, these findings shed light on the neuroprotective effect of CUR and CS.CUR.NPs against stress-induced neurobehavioral and neurochemical deficits and protection against stress-associated gastric ulcer. Moreover, we explored a potential crosslink between neuroinflammation, U-STAT3, NF-κB, and GFAP in brain dysfunction resulted from CRS.

Topics: Animals; Behavior, Animal; Chitosan; Cognitive Dysfunction; Cold Temperature; Curcumin; Glial Fibrillary Acidic Protein; Inflammation; Nanoparticle Drug Delivery System; Neuroprotective Agents; Oxidation-Reduction; Pain; Rats; STAT3 Transcription Factor; Stomach; Stomach Ulcer; Stress, Physiological

Traumatic brain injury (TBI) affects approximately 50% of the world population at some point in their lifetime. To date, there are no effective treatments as most of the damage occurs due to secondary effects through a variety of pathophysiological pathways. The phytoceutical curcumin has been traditionally used as a natural remedy for numerous conditions including diabetes, inflammatory diseases, and neurological and neurodegenerative disorders. We have carried out a system pharmacology study to identify potential targets of a difluorinated curcumin analogue (CDF) that overlap with those involved in the pathophysiological mechanisms of TBI. This resulted in identification of 312 targets which are mostly involved in G protein-coupled receptor activity and cellular signalling. These include adrenergic, serotonergic, opioid and cannabinoid receptor families, which have been implicated in regulation of pain, inflammation, mood, learning and cognition pathways. We conclude that further studies should be performed to validate curcumin as a potential novel treatment to ameliorate the effects of TBI.

Topics: Brain Injuries, Traumatic; Curcumin; Inflammation; Network Pharmacology; Oxidative Stress; Protein Interaction Maps; Receptors, G-Protein-Coupled; Signal Transduction

Poly-L-lactic acid (PLLA) is considered to be a promising candidate material for biodegradable vascular scaffolds (BVS) in percutaneous coronary intervention (PCI). But, PLLA-BVS also faces the challenge of thrombosis (ST) and in-stent restenosis (ISR) caused by in-stent neo-atherosclerosis (ISNA) associated with inflammatory reactions in macrophage-derived foam cells. Our previous studies have confirmed that curcumin alleviates PLLA-induced injury and inflammation in vascular endothelial cells, but it remains unclear whether curcumin can alleviate the effect of inflammatory reactions in macrophage-derived foam cells while treated with degraded product of PLLA. In this study, PLLA-BVS was implanted in the porcine coronary artery to examine increased macrophages and inflammatory cytokines such as NF-κb and TNF-α by histology and immunohistochemistry. In vitro, macrophage-derived foam cells were induced by Ox-LDL and observed by Oil Red Staining. Foam cells were treated with pre-degraded PLLA powder, curcumin and PPARγ inhibitor GW9662, and the expression of IL-6, IL-10, TNF-α, NF-κb, PLA2 and PPARγ were investigated by ELISA or RT-qPCR. This study demonstrated that the macrophages and inflammatory factors increased after PLLA-BVS implantation in vivo, and foam cells derived from macrophages promoted inflammation by products of PLLA degradation in vitro. This present study was found that the inflammation of foam cells at the microenvironment of PLLA degraded products were significantly increased, and curcumin can attenuate the inflammation caused by the PLLA degradation via PPARγ signal pathway. In addition, curcumin should be further studied experimentally in vivo experiments on animal models as a potential therapeutic to reduce ISNA of PLLA-BVS. Graphical abstract.

Topics: Animals; Atherosclerosis; Curcumin; Endothelial Cells; Foam Cells; Inflammation; Macrophages; Percutaneous Coronary Intervention; Polyesters; PPAR gamma; Signal Transduction; Swine

The activation of NLRP3 results in the assembly of inflammasome that regulates caspase-1 activation and the subsequent secretion of bioactive interleukin (IL)-1β. Excessive activation of the NLRP3 inflammasome is mechanistically linked to diverse pathophysiological conditions, including airway inflammation. Here, we discovered that

Topics: Animals; Antioxidants; Caspase 1; Caspases; Curcuma; Curcumin; Inflammasomes; Inflammation; Interleukin-1beta; Macrophages; Mice; Nanoparticles; NF-kappa B; NLR Family, Pyrin Domain-Containing 3 Protein; Silicon Dioxide

Curcumin is proven to have potent anti-inflammatory activity, but its low water solubility and rapid degradation in physiological conditions limit its clinical use, particularly in intravenous drug delivery. In this study, we fabricated rod-shaped, acid-labile nanogels, using high biosafe and biocompatible polymers, for intravenous application in systemic inflammation treatment. The constituent polymers of the nanogels were prepared via the conjugation of vitamin B

Topics: Curcumin; Humans; Inflammation; Nanogels; Polyethylene Glycols; Polyethyleneimine; Polymers; Pyridoxal; Pyridoxamine; Schiff Bases; Solvents; Vitamins

Curcumin has attracted much attention due to its wide range of therapeutic effects. In this study, we used serum collected from patients undergoing one-lung ventilation (OLV) to establish an in vitro acute lung injury (ALI) model to explore the potential protective mechanism of curcumin on ALI. Our study provides a new reference for the prevention and treatment of ALI induced by OLV.. A549 cells were treated with 20% serum from patients undergoing OLV to establish an in vitro ALI model. Curcumin, at a dose of 40 μg/ml, was administered two hours prior to this model. The levels of inflammation and oxidative stress markers were observed by Western blot, qRT-PCR, ELISA and reactive oxygen species assay. Additionally, the expression of peroxiredoxin 6 (Prdx6) and proteins involved in the NF-κB signaling pathway was evaluated.. Twenty percent of serum collected from patients undergoing OLV downregulated the expression of Prdx6, leading to the activation of the NF-κB signaling pathway, which was associated with the subsequent overproduction of inflammatory cytokines and reactive oxygen species. Pretreatment with curcumin restored Prdx6 downregulation and inhibited NF-κB pathway activation by suppressing the nuclear translocation of P65, eventually reducing inflammation and oxidative stress damage in A549 cells.. Prdx6 mediated the protective function of curcumin by inhibiting the activation of the NF-κB pathway in ALI in vitro.

Topics: Acute Lung Injury; Curcumin; Humans; Inflammation; Lipopolysaccharides; NF-kappa B; One-Lung Ventilation; Peroxiredoxin VI; Reactive Oxygen Species

Pancreatic adenocarcinoma is by far the deadliest type of cancer. Inflammation is one of the important risk factors in tumor development. However, it is not yet clear whether deterioration in pancreatic cancer patients is related to inflammation, as well as the underlying mechanism. In addition, JNK is abnormally activated in pancreatic cancer cells and the JNK inhibitor C66 reduces the inflammatory microenvironment in the tumor. Therefore, the aim of this study was to evaluate the role of C66 in the proliferation and migration of pancreatic cancer. Our results showed that various inflammatory cytokines, such as IL-1β, IL-6, IL-8, and IL-15, were more expressed in pancreatic cancer than in the matching normal tissue. Furthermore, C66, a curcumin analogue with good anti-inflammatory activity, inhibited the proliferation and migration of pancreatic cancer cells in a dose-dependent manner, and effectively inhibited the expression of the above inflammatory factors. Our previous research demonstrated that C66 prevents the inflammatory response by targeting JNK. Therefore, in this study, JNK activity in pancreatic cancer cells was investigated, revealing that JNK was highly activated, and the treatment with C66 inhibited the phosphorylation of JNK. Next, shJNK was used to knockdown JNK expression in pancreatic cancer cells to further confirm the role of JNK in the proliferation and migration of this tumor, as well as in the inflammatory tumor microenvironment (TME). The results demonstrated that JNK knockdown could significantly inhibit the proliferation and migration of pancreatic cancer. Moreover, the low JNK expression in pancreatic cancer cells significantly inhibited the expression of various inflammatory factors. These results indicated that C66 inhibited the progression of pancreatic cancer through the inhibition of JNK-mediated inflammation.

Topics: Adenocarcinoma; Animals; Curcumin; Humans; Inflammation; JNK Mitogen-Activated Protein Kinases; Mice; Mice, Inbred C57BL; Pancreatic Neoplasms; Tumor Microenvironment

Persistent injuries and chronic inflammation paired with dysregulated healing process in the lungs leads to scarring and stiffening of the tissue leading to a condition called pulmonary fibrosis. There is no efficacious therapy against the condition because of the poorly understood pathophysiology of the disease. Curcumin is well known anti-inflammatory natural compound and is shown to have beneficial effects in many diseases. It is also reported to show antifibrotic activities in pulmonary fibrosis. There are evidences that fibrinolytic system plays a crucial role in the development of pulmonary fibrosis. We aimed to see whether curcumin could regulate inflammation and fibrinolysis in murine model of pulmonary fibrosis. We prepared BLM induced pulmonary fibrosis model by administering BLM at a dose of 2 mg/ kg bodyweight. Curcumin (75 mg/kg body wt) was instilled intraperitoneally on different time points. The effect of curcumin on inflammatory cytokines and fibrinolytic system was studied using molecular biology techniques like RT-PCR, western blot and immunohistochemistry/immunofluorescence. We observed that BLM brought changes in the expressions of components in the fibrinolytic system, i.e. BLM favoured fibrin deposition by increasing the expression of PAI-1 (plasminogen activator inhibitor) and decreasing the expression of uPA (Urokinase plasminogen activator) and uPAR (Urokinase plasminogen activator receptor). We also demonstrate that curcumin could restore the normal expression of fibrinolytic components, uPA, uPAR and PAI-1. Curcumin could also minimize the expression of key enzymes in tissue remodeling in pulmonary fibrosis, MMP-2 and MMP-9, which were elevated in the BLM treated group. Our data suggest that curcumin exerts an anti-inflammatory and antifibrotic effect in lungs. We highlight curcumin as a feasible adjuvant therapy option against pulmonary fibrosis.

Topics: Animals; Curcumin; Cytokines; Fibrinolysis; Inflammation; Mice; Plasminogen Activator Inhibitor 1; Pulmonary Fibrosis; Urokinase-Type Plasminogen Activator

Neurodegenerative diseases have become increasingly prevalent in the aged population. Rheumatoid arthritis (RA) is an autoimmune disease that causes systemic inflammation, damaging the neurons. However, only a few treatment options can reduce RA-induced neurodegeneration. This study aimed to evaluate whether adipose-derived stem cells (ADSCs) pretreated with curcumin could ameliorate RA-induced neurodegenerative illness in an RA rat model. Wistar rats were randomly classified into the following four groups: control, RA, RA + ADSC (1 × 10

Topics: Adipose Tissue; Animals; Arthritis, Rheumatoid; Brain; Curcumin; Inflammation; Neuroprotection; Rats; Rats, Wistar; Stem Cells

Being anti-inflammatory and an antioxidant in nature, curcumin has been studied for its anti-asthmatic effects, but its impact on silicosis has not been investigated before. It is a form of occupational lung illness caused by inhaling crystalline silica. It is particularly common among those who work in construction-related sectors. Therefore, present study has been undertaken to investigate impact of intranasal curcumin on silica induced lung damage in mice model of silicosis.. Mice model of silicosis was developed by intranasal silica instillation (2.5 mg/mice) for different durations mainly 7, 14 and 21 days, where the longest duration of silica exposure (21 days) mimics chronic occupational exposure of silica dust leading to silicosis. Curcumin (5 mg/kg,i.n) and /or dexamethasone, a known corticosteroid (10 mg/kg,i.p) was administered an hour prior to silica administration.. Present study revealed silica induced lung damage in the mice model of silicosis characterized by airway inflammation, collagen deposition and enhanced expression of fibrosis markers (MMP-9, α-SMA, Hydroxyproline), which were significantly reduced in curcumin treatment groups. Inhibitory effects of curcumin were compared with standard drug, dexamethasone, a corticosteroid and was found better in protecting structural alterations in the lung. Damaged and abnormal mitochondria (enlarged and irregular shapes) were observed in silicosis group which were reduced in curcumin and dexamethasone treatment groups as revealed in transmission electron microscopic studies.. Present study shows protective effects of intranasal curcumin on silica-induced airway inflammation and structural changes thereby lung damage. Hence, it can be considered as an alternative and complementary medication for silicosis.

Topics: Animals; Curcumin; Dexamethasone; Disease Models, Animal; Inflammation; Lung; Mice; Silicon Dioxide; Silicosis

Acute myocardial dysfunction in patients with sepsis is attributed to oxidative stress, inflammation, and cardiomyocyte loss; however, specific drugs for its prevention are still lacking. Tetrahydrocurcumin (THC) has been proven to contribute to the prevention of various cardiovascular diseases by decreasing oxidative stress and inflammation. This study was performed to investigate the functions and mechanism of action of THC in septic cardiomyopathy.. After the oral administration of THC (120 mg/kg) for 5 consecutive days, a mouse model of sepsis was established via intraperitoneal lipopolysaccharide (LPS, 10 mg/kg) injection. Following this, cardiac function was assessed, pathological section staining was performed, and inflammatory markers were detected.. Myocardial systolic function was severely compromised in parallel with the accumulation of reactive oxygen species and enhanced cardiomyocyte apoptosis in mice with sepsis. These adverse changes were markedly reversed in response to THC treatment in septic mice as well as in LPS-treated H9c2 cells. Mechanistically, THC inhibited the release of pro-inflammatory cytokines, including tumor necrosis factor alpha, interleukin (IL)-1β, and IL-6, by upregulating mitogen-activated protein kinase phosphatase 1, to block the phosphorylation of c-Jun N-terminal kinase (JNK) and extracellular signal-regulated protein kinase (ERK). Additionally, THC enhanced the levels of antioxidant proteins, including nuclear factor-erythroid 2-related factor 2, superoxide dismutase 2, and NAD(P)H quinone oxidoreductase 1, while decreasing gp91. Our findings indicate that THC exhibited protective potential against septic cardiomyopathy by reducing oxidative stress and inflammation through the regulation of JNK/ERK signaling. The findings of this study provide a basis for the further evaluation of THC as a therapeutic agent against septic cardiomyopathy.

Topics: Animals; Cardiomyopathies; Curcumin; Inflammation; Lipopolysaccharides; MAP Kinase Signaling System; Mice; Oxidative Stress; Sepsis

Therapeutic benefits of curcumin for inflammatory diseases have been demonstrated. However, curcumin's potential as a clinical therapeutic has been hindered due to its low solubility and stability in vivo. We hypothesized that a hybrid curcumin carrier that incorporates albumin-binding and extracellular vesicle (EV) encapsulation could effectively address the current challenges of curcumin delivery. We further postulated that using dissolvable microneedle arrays (dMNAs) for local delivery of curcumin-albumin-EVs (CA-EVs) could effectively control skin inflammation in vivo. Mild sonication was used to encapsulate curcumin and albumin into EVs, and the resulting CA-EVs were integrated into tip-loaded dMNAs. In vitro and in vivo studies were performed to assess the stability, cellular uptake, and anti-inflammatory bioactivity of dMNA-delivered CA-EVs. Curcumin in CA-EVs exhibited at least five-fold higher stability in vitro than naïve curcumin or curcumin-EVs without albumin. Incorporating CA-EVs into dMNAs did not alter their cellular uptake or anti-inflammatory bioactivity. The dMNA embedded CA-EVs retained their bioactivity when stored at room temperature for at least 12 months. In rat and mice models, dMNA delivered CA-EVs suppressed and significantly reduced lipopolysaccharide and Imiquimod-triggered inflammation. We conclude that dMNA delivery of CA-EVs has the potential to become an effective local-delivery strategy for inflammatory skin diseases. STATEMENT OF SIGNIFICANCE: We introduce and evaluate a skin-targeted delivery system for curcumin that synergistically combines albumin association, extracellular-vesicle encapsulation, and dissolvable microneedle arrays (dMNAs) . In vitro, curcumin-albumin encapsulated extracellular vesicles (CA-EVs) inhibit and reverse the LPS-triggered expression of inflammatory transcription factor NF-κB. The integration of CA-EVs into dMNAs does not affect them physically or functionally. Importantly, dMNAs extend EV storage stability for at least 12 months at room temperature with minimal loss in their bioactivity. We demonstrate that dMNA delivered CA-EVs effectively block and reverse skin inflammation in vivo in mouse and rat models.

Topics: Albumins; Animals; Anti-Inflammatory Agents; Curcumin; Extracellular Vesicles; Inflammation; Mice; Rats

As a chronic skin disease, psoriasis is a relatively common disease among various types of skin diseases. Because this disease is often distributed throughout the patient's body and is prone to develop, it is difficult to guarantee the quality of life and physical and mental health of patients with this disease. The purpose of this article is to investigate whether curcumin can effectively inhibit the NLRP3 inflammatory body and thereby reduce the inflammation in the mouse psoriasis model. Through the use of the curcumin gel prepared and the mouse psoriasis model, the percutaneous administration was used to investigate the mechanism and mechanism of curcumin's effect on reducing inflammation in the mouse psoriasis model. In addition, in order to better explore the curative effect of curcumin on psoriasis, related experiments were conducted by setting up a control group and an experimental group. The results show that curcumin has a good inhibitory effect on NLRP3 inflammatory bodies. Curcumin can not only reduce the NLRP3 expression and inhibit the inflammation caused by IL-22 and IL-18 but also reduce the damage of psoriasis. 22 Induced phosphorylation of STAT3 almost completely inhibits phosphorylation in normal cells. Among them, curcumin inhibited IL-22-induced phosphorylation of STAT3 up to 95.6%, and inhibited IL-22 and IL-18 by about 47%.

Topics: Animals; Curcumin; Disease Models, Animal; Inflammation; Interleukin-18; Mice; NLR Family, Pyrin Domain-Containing 3 Protein; Psoriasis; Quality of Life

Demyelination disease as diabetes mellitus (DM) complication is characterized by apoptosis of Schwann cells (SCs) and several reports have demonstrated that high glucose content can induce an inflammation response and lead to the apoptosis of SCs. For NF-κB plays a pivotal role in the inflammatory response, hence we hypothesized that high glucose content can induce inflammation though the NF-κB pathway. First we verified that 150 mM high glucose can increase the expression of cleaved caspase 3, interleukin (IL)- 1β, Cyto-C and NF-κB with time through Western blot and increase the apoptosis of RSC96s through Flow Cytometry. Then we found that high glucose can increase the nuclear translocation NF-κB through confocal system which can promote the expression of inflammation genes such as IL-1β. Curcumin has been reported to possess anti-inflammation activities to protect cells. In this study, we found that application with 25 μM curcumin could alleviate the inflammation response and protect the cells from apoptosis. We revealed that the expression of NF-κB and p-NF-κB was decreased and the translocation was also inhibited after curcumin application. Accordingly, the secretion of IL-1β and the apoptosis of RSC96s induce by high glucose was suppressed. Our cumulative findings suggest that curcumin can protect SCs from apoptosis through the inhibition of the inflammatory response though the NF-κB pathway.

Topics: Apoptosis; Curcumin; Glucose; Humans; Inflammation; NF-kappa B; Schwann Cells; Signal Transduction

The epithelial cell is the main basic unit of the udder in which milk synthesis takes place. Curcumin is well known for its antioxidant, anti-apoptotic, and anti- inflammatory properties. The present study was performed to test whether in vitro curcumin supplementation can alleviate the unfavorable impact of hyperthermia on buffalo mammary epithelial cells (BuMECs). The spontaneously immortalized BuMECs were divided into 7 groups (n = 9); 1) unstressed BuMECs (negative control, 37 °C); 2) BuMECs exposed to hyperthermia without curcumin treatment (positive control); 3-7) BuMECs cultured with different concentrations of curcumin (5, 10, 20, 40 and 60 μM), respectively, followed by hyperthermic exposure (42ºC) for 1 h and then returned to 37ºC. Changes in viability (MTT assay), proliferation (BrdU colorimetric immunoassay) and concentrations of antioxidant enzymes, CAT, and SOD (ELISA) of BuMECs were recorded. The gene expression study was performed using qRT-PCR. Lower concentrations of curcumin (5, 10 μM) maintained viability, enhanced proliferation, and content of antioxidant enzymes of heat stressed BuMECs. Curcumin induced thermotolerance and antioxidant status by upregulating the expression of antioxidants genes, anti-apoptotic genes and heat shock proteins in heat stressed BuMECs compared to the positive control group. Besides, curcumin reduced apoptosis and inflammation in BuMECs exposed to hyperthermia by downregulating the expression of genes and transcriptional factors associated with apoptosis and inflammatory immune response. The results reveal the potential roles of curcumin in eliminating the negative impact of hyperthermia on BuMECs by regulating the pathways of apoptosis, inflammation, and oxidative stress.

Topics: Animals; Antioxidants; Apoptosis; Bromodeoxyuridine; Buffaloes; Curcumin; Epithelial Cells; Heat-Shock Proteins; Heat-Shock Response; Inflammation; Oxidative Stress; Superoxide Dismutase; Thermotolerance

The aim of the study was to evaluate the effect of systemic curcumin administration on the severity of apical periodontitis (AP).. Forty male Wistar rats weighing 250-280 g each, age 2.5 months, were distributed into four groups (n = 10): control untreated rats (C), control rats treated with curcumin (CUR), rats with pulp exposure-induced apical periodontitis (AP) and rats with pulp exposure-induced apical periodontitis treated with curcumin (AP-CUR). Curcumin treatment was administered orally once daily for 15 days before pulp exposure and continued for 30 days after pulp exposure. The rats were sacrificed at 30 days, and the jaws were collected and reconstructed in a programme specific for micro-CT. The jaws were processed for analysis of the inflammatory process using haematoxylin and eosin staining and immunohistochemical assays for interleukin tumour necrosis factor alpha (TNF-α), interleukin (Il)-6 and Il-1β. Tartrate-resistant acid phosphatase (TRAP) and osteocalcin (OCN) staining were used to analyse the resorptive process on the bone surface of periapical area. Kruskal-Wallis with Dunn's test was performed for nonparametric data and anova with Tukey's test for parametric data, p < .05.. Micro-CT revealed no statistically significant differences in bone resorption between the AP and AP-CUR groups (p > .05). The levels of inflammatory cell infiltration and immunoreactivity for the proinflammatory cytokines TNF-α, Il-6 and Il-1β were significantly higher in the periapical lesions of the AP group than in the AP-CUR group (p < .05). The number of TRAP-positive multinucleated cells was higher in the AP group than in the AP-CUR group (p < .05). In OCN-positive cells, no differences were observed between the AP and AP-CUR groups (p > .05).. Oral supplementation with curcumin had a significant effect on the AP severity in rats, suggesting an anti-inflammatory effect of curcumin on AP development.

Topics: Animals; Anti-Inflammatory Agents; Curcumin; Cytokines; Eosine Yellowish-(YS); Inflammation; Interleukin-6; Male; Osteocalcin; Periapical Periodontitis; Rats; Rats, Wistar; Tartrate-Resistant Acid Phosphatase; Tumor Necrosis Factor-alpha

In general, starch, as a complex carbohydrate, is the most economical energy source in aquaculture for its relatively low cost. However, excessive dietary levels of carbohydrate result in pathological conditions. An 8-week feeding trial with CT (control diet, containing 21% carbohydrate), HC (a high-carbohydrate diet, containing 50% carbohydrate) and HCR (a HC diet supplemented with 0.015% Rhizoma curcumae Longae) was performed to investigate the protective effect of curcumin on high-carbohydrate-induced hepatic oxidative stress and intestine lesion in juvenile Trachinotus ovatus. In the current study, HC group significantly decreased WGR, SGR, plasma CAT activity, intestinal C4 levels, hepatic Nrf2, Keap1, Bach1, HO1, CAT, and GPX mRNA expression as well as ZO-1, Occludin, and Claudin-3, TGF-β mRNA transcription levels, while the opposite was true for plasma AST activity, hepatic MDA contents, intestinal Claudin-15, NF-κB, IL-1β, IL-6, and TNF-α mRNA expression. In contrast with the HC group, the HCR group significantly increased the activities of hepatic CAT, SOD, intestinal C3, C4, IgG and LZM levels, hepatic Nrf2, Bach1, CAT, and GPX mRNA expression as well as intestinal ZO-1, Occludin, Claudin-3, TGF-β and IL-10 mRNA expression levels, but the opposite trend was found in plasma triglyceride content, hepatic lipid deposition, hepatic Keap1 mRNA level as well as intestinal NF-κB, IL-6. In conclusion, high-carbohydrate diet can cause detrimental effect on physiological health status in Trachinotus ovatus, while adding Rhizoma curcumae Longae can improve hepatic and intestinal health status via attenuating the oxidative stress, inflammation, and reducing lipid deposition.

Topics: Animal Feed; Animals; Claudin-3; Curcumin; Diet; Dietary Carbohydrates; Dietary Supplements; Immunoglobulin G; Inflammation; Interleukin-10; Interleukin-6; Kelch-Like ECH-Associated Protein 1; Lipids; NF-E2-Related Factor 2; NF-kappa B; Occludin; Oxidative Stress; Perciformes; RNA, Messenger; Starch; Superoxide Dismutase; Transforming Growth Factor beta; Triglycerides; Tumor Necrosis Factor-alpha

Cardiac inflammation is an important pathological process in diabetic cardiomyopathy (DCM). Curcumin is a natural compound found in the rhizome of Curcuma longa and has been shown to possess multifunctional bioactivities. In the present study, we identified a new curcumin-derived compound, JM-2, and investigated its therapeutic effects against DCM in mouse models of streptozotocin-induced type 1 diabetes mellitus (T1DM) and HFD-induced type 2 diabetes (T2DM). Treatment with JM-2 (10 mg/kg) prevented cardiac functional and structural deficits effectively and reduced cardiac inflammation and fibrosis. JM-2 administration attenuated DCM by inhibiting nuclear factor kappa-B (NF-κB) activation in the heart of both models. In addition, treatment with JM-2 completely prevented the increase in proinflammatory factors and macrophage infiltration in T1DM and T2DM mice. RNA-seq analysis showed that the anti-inflammatory activity of JM-2 was associated with the inhibition of NF-κB activation. In vitro, JM-2 suppressed high glucose (HG)-induced myocardial hypertrophy and fibrosis in H9c2 cells, accompanied by inhibition of HG-induced NF-κB activation. Collectively, our results showed that JM-2, a new curcumin analog, provides strong protection against DCM via inhibition of the NF-κB-mediated inflammation. In summary, our data suggest that the curcumin analog JM-2 may be a potential therapeutic agent for DCM.

Topics: Animals; Curcumin; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Cardiomyopathies; Fibrosis; Inflammation; Mice; Myocytes, Cardiac; NF-kappa B

Chronic actinic dermatitis (CAD) is an abnormally proliferating photoallergic skin disease. Dysregulated inflammation and oxidative stress are the immediate factors in the abnormal proliferation of keratinocytes. This study aimed to investigate the effect of curcumin on the aberrant proliferation of keratinocytes in an. Curcumin weakened UV-mediated inflammation, proliferation, and oxidative stress and impaired apoptosis in keratinocytes. UV boosted SPAG5/FOXM1 expression in cells, while curcumin concentration-dependently retarded SPAG5/FOXM1 expression. Overexpression of SPAG5/FOXM1 fostered UV-mediated inflammation, proliferation, oxidative stress, and intensified apoptosis, whereas curcumin mostly reversed the SPAG5/FOXM1-mediated effects. In addition, knocking down SPAG5/FOXM1 ameliorated UV-mediated keratinocyte dysfunction, whereas curcumin failed to exert further protective effects in cells with knockdown of SPAG5/FOXM1.. Curcumin modulated proliferation, inflammation, oxidative stress, and apoptosis of keratinocytes by restraining the SPAG5/FOXM1 axis.

Topics: bcl-2-Associated X Protein; Cell Cycle Proteins; Cell Proliferation; Curcumin; Cyclooxygenase 2; Forkhead Box Protein M1; Humans; Inflammation; Interleukin-18; Interleukin-6; Kelch-Like ECH-Associated Protein 1; Keratinocytes; Matrix Metalloproteinase 1; Matrix Metalloproteinase 9; NF-E2-Related Factor 2; NF-kappa B; Oxidative Stress; Oxygen; Photosensitivity Disorders; Reactive Oxygen Species; Superoxide Dismutase; Tumor Necrosis Factor-alpha

The dramatic upsurge of Clostridioides difficile infection (CDI) by hypervirulent isolates along with the paucity of effective conventional treatment call for the development of new alternative medicines against CDI. The inhibitory effects of curcumin (CCM) and capsaicin (CAP) were investigated on the activity of toxigenic cell-free supernatants (Tox-S) of C. difficile RT 001, RT 126 and RT 084, and culture-filtrate of C. difficile ATCC 700057.. Cell viability of HT-29 cells exposed to varying concentrations of CCM, CAP, C. difficile Tox-S and culture-filtrate was assessed by MTT assay. Anti-inflammatory and anti-apoptotic effects of CCM and CAP were examined by treatment of HT-29 cells with C. difficile Tox-S and culture-filtrate. Expression of BCL-2, SMAD3, NF-κB, TGF-β and TNF-α genes in stimulated HT-29 cells was measured using RT-qPCR.. C. difficile Tox-S significantly (P < 0.05) reduced the cell viability of HT-29 cells in comparison with untreated cells. Both CAP and CCM significantly (P < 0.05) downregulated the gene expression level of BCL-2, SMAD3, NF-κB and TNF-α in Tox-S treated HT-29 cells. Moreover, the gene expression of TGF-β decreased in Tox-S stimulated HT-29 cells by both CAP and CCM, although these reductions were not significantly different (P > 0.05).. The results of the present study highlighted that CCM and CAP can modulate the inflammatory response and apoptotic effects induced by Tox-S from different clinical C. difficile strains in vitro. Further studies are required to accurately explore the anti-toxin activity of natural components, and their probable adverse risks in clinical practice.

Topics: Anti-Inflammatory Agents; Apoptosis; Bacterial Toxins; Capsaicin; Clostridioides; Clostridioides difficile; Clostridium Infections; Curcumin; Humans; Inflammation; NF-kappa B; Proto-Oncogene Proteins c-bcl-2; Transforming Growth Factor beta; Tumor Necrosis Factor-alpha

The role of curcumin in multiple human diseases was widely reported, including arteriosclerosis (AS). We aimed to investigate the correlation between curcumin and AS-related microRNAs (miRNAs) to find out more underlying mechanism of curcumin used in AS.. Cell proliferation and apoptosis were determined using CCK-8 assay, EdU staining assay, flow cytometry, and western blot for the detection of PCNA and Bax protein expression in human umbilical vein endothelial cells (HUVECs). Inflammation response was evaluated using ELISA kits, and oxidative stress was evaluated by detecting SOD activity and MDA level using the matched commercial kits. RT-qPCR analysis was applied for miR-599 and MYD88 mRNA level measurement.. Curcumin treatment and miR-599 overexpression could promote cell proliferation, and inhibit cell apoptosis, inflammation response and oxidative stress, thereby alleviating ox-LDL-induced cell damage in HUVECs. Mir-599 was lowly expressed and MYD88 was highly expressed in AS patients and AS cell model. Curcumin could modulate miR-599 to exert the protective effect on ox-LDL-caused cell damage, and miR-599 directly targeted MYD88 to alleviate ox-LDL-caused cell damage in HUVECs. Curcumin targeted miR-599 to regulate MYD88 expression, thereby inactivating the NF-κB pathway in AS cell model.. Our findings illustrated that curcumin exhibited anti-AS effect through the miR-599/MYD88 axis and thereby inhibiting the NF-κB pathway.

Topics: Apoptosis; bcl-2-Associated X Protein; Curcumin; Human Umbilical Vein Endothelial Cells; Humans; Inflammation; Lipoproteins, LDL; MicroRNAs; Myeloid Differentiation Factor 88; NF-kappa B; Proliferating Cell Nuclear Antigen; RNA, Messenger; Superoxide Dismutase

Comorbidity of Opisthorchis viverrini (OV) infection and nonalcoholic fatty-liver disease (NAFLD) enhances NAFLD progression to nonalcoholic steatohepatitis (NASH) by promoting severe liver inflammation and fibrosis. Here, we investigated the effect of supplementation with curcumin-loaded nanocomplexes (CNCs) on the severity of NASH in hamsters.. Hamsters were placed in experimental groups as follows: fed standard chow diet (normal control, NC); fed only high-fat and high-fructose (HFF) diet; O. viverrini-infected and fed HFF diet (HFFOV); group fed with blank nanocomplexes (HFFOV+BNCs); groups fed different doses of CNCs (25, 50 and 100 mg/kg body weight: HFFOV+CNCs25; HFFOV+CNCs50; HFFOV+CNCs100, respectively) and a group given native curcumin (HFFOV+CUR). All treatment were for three months.. The HFF group revealed NAFLD as evidenced by hepatic fat accumulation, ballooning, mild inflammation and little or no fibrosis. These changes were more obvious in the HFFOV group, indicating development of NASH. In contrast, in the HFFOV+CNCs50 group, histopathological features indicated that hepatic fat accumulation, cell ballooning, cell inflammation and fibrosis were lower than in other treatment groups. Relevantly, the expression of lipid-uptake genes, including fatty-acid uptake (cluster of differentiation 36), was reduced, which was associated with the lowering of alanine aminotransferase, total cholesterol and triglyceride (TG) levels. Reduced expression of an inflammation marker (high-mobility group box protein 1) and a fibrosis marker (alpha smooth-muscle actin) were also observed in the HFFOV+CNCs50 group.. CNCs treatment attenuates the severity of NASH by decreasing hepatic steatosis, inflammation, and fibrosis as well as TG synthesis. CNCs mitigate the severity of NASH in this preclinical study, which indicates promise for future use in patients.

Topics: Actins; Alanine Transaminase; Animals; Cholesterol; Cricetinae; Curcumin; Diet, High-Fat; Disease Models, Animal; Fructose; Humans; Inflammation; Lipids; Liver; Non-alcoholic Fatty Liver Disease; Opisthorchiasis; Opisthorchis; Triglycerides

The pathogenesis of gastric cancer is a multistage process that involves glucose metabolism, inflammation, oxidative damage, angiogenesis, autophagy, and apoptosis. Moreover, microRNA-340 (miR340) also plays a vital role in tumorigenesis and the biology of gastric cancer as an epigenetic factor. It seems that the use of ketogenic diets (KDs) and plant extracts that have antitumor, anti-inflammatory, and antioxidant properties can be good treatment options to cure gastric cancer. The aim of this study was to investigate the role of miR-340 on pathways involved in the pathogenesis of gastric cancer and the improving effects of the KD, Oldenlandia diffusa extract (ODE), and curcumin in the animal model of gastric cancer. One hundred and ten male Wistar rats were divided into control and treatment groups. The expression of miR-340 along with genes involved in inflammation, oxidative damage, angiogenesis, and apoptosis were assessed. The results showed that the KD and different doses of curcumin and ODE in a dose-dependent behavior could induce apoptosis and the expression of the Akt/mTORC1 pathway and inhibit inflammation, oxidative damage, and angiogenesis in the gastric tissue of rats with cancer. In addition, there was no significant difference between cancer groups receiving ODE and curcumin. These results also showed that consumption of KD could significantly increase the efficacy of ODE and curcumin which may be due to increasing miR-340 expression. The results of this study suggested well that the KD along with conventional therapies in traditional medicine can be a useful solution for the prevention and treatment of gastric cancer. PRACTICAL APPLICATIONS: Gastric cancer is the third leading cause of cancer death, and genetic and epigenetic factors, including miR-340, are involved in its pathogenesis. However, the use of ketogenic diets (KDs) and plant products such as curcumin and Oldenlandia diffusa extract (ODE) can play an effective role in inhibiting tumorigenesis in some cancers. Our results showed that the KD and different doses of curcumin and ODE could induce apoptosis and the expression of the Akt/mTORC1 pathway and inhibit inflammation, oxidative damage, and angiogenesis in the gastric tissue. Moreover, the KD could significantly increase the efficacy of ODE and curcumin which may be due to an increase in miR-340 expression. These findings provide novel perceptions about the mechanisms of the KD, curcumin, and ODE to cure gastric cancer. It

Topics: Animals; Apoptosis; Autophagy; Carcinogenesis; Curcumin; Diet, Ketogenic; Inflammation; MicroRNAs; Oldenlandia; Oxidative Stress; Plant Extracts; Proto-Oncogene Proteins c-akt; Rats; Rats, Wistar; Stomach Neoplasms

The present study evaluated the anti-inflammatory and analgesic effects of conventional curcumin (cC) and curcumin nanoparticles (nC) associated with diclofenac sodium (D) in experimental acute inflammation (AI) induced by carrageenan administration. Seven groups of eight randomly selected Wistar-Bratislava white rats were evaluated. One group was the control (C), and AI was induced in the other six groups. The AI group was treated with saline solution, the AID group was treated with D, the AIcC200 and AInC200 groups were treated with cC and nC, respectively, while AIcC200D and AInC200D were treated with cC and nC, respectively, both associated with D. Conventional curcumin, nC, and D were administered in a single dose of 200 mg/kg b.w. for cC and nC and 5 mg/kg b.w. for D. Association of cC or nC to D resulted in significant antinociceptive activity, and improved mechanical pressure stimulation and heat thresholds at 3, 5, 7 and 24 h (p < 0.03). The association of cC and nC with D (AIcC200D and AInC200D groups) showed significantly lower plasma and tissue levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β) up to 2.5 times, with the best results in the group who received nC. Moreover, AInC200D presented the least severe histopathological changes with a reduced level of inflammation in the dermis and hypodermis. The combination of nC to D showed efficiency in reducing pain, inflammatory cytokines, and histological changes in acute inflammation.

Topics: Analgesics; Animals; Anti-Inflammatory Agents; Carrageenan; Curcumin; Cytokines; Diclofenac; Inflammation; Interleukin-1beta; Interleukin-6; Nanoparticles; Rats; Rats, Wistar; Saline Solution; Tumor Necrosis Factor-alpha

Infection, trauma, and autoimmunity trigger tissue inflammation, often leading to pain and loss of function. Therefore, approaches to control inflammation based on nanotechnology principles are being developed in addition to available methods. The metal-based nanoparticles are particularly attractive due to the ease of synthesis, control over physicochemical properties, and facile surface modification with different types of molecules. Here, we report curcumin conjugated silver (Cur-Ag) nanoparticles synthesis, followed by their surface functionalization with isoniazid, tyrosine, and quercetin, leading to Cur-AgINH, Cur-AgTyr, and Cur-AgQrc nanoparticles, respectively. These nanoparticles possess radical scavenging capacity, haemocompatibility, and minimal cytotoxicity to macrophages. Furthermore, the nanoparticles inhibited the secretion of pro-inflammatory cytokines such as interleukin-6, tumor necrosis factor-α, and interleukin-1β from macrophages stimulated by lipopolysaccharide (LPS). The findings reveal that the careful design of surface corona of nanoparticles could be critical to increasing their efficacy in biomedical applications.

Topics: Curcumin; Cytokines; Homeostasis; Humans; Inflammation; Interleukin-1beta; Interleukin-6; Isoniazid; Lipopolysaccharides; Metal Nanoparticles; Nanoparticles; Quercetin; Silver; Tumor Necrosis Factor-alpha; Tyrosine

Age-related decrements in the central nervous system (CNS) are thought to result from: (1) increased susceptibility to and accumulating effects of free radicals and inflammation; and (2) dysregulation in Ca2+ homeostasis, which affects numerous signaling pathways. Certain bioactive phytochemicals exhibit potent anti-inflammatory activities which may mitigate these age-related CNS decrements. This study investigated the individual and combination effects of green tea catechin (epigallocatechin gallate, EGCG), curcumin from turmeric, and broccoli sprouts which contain the isothiocyanate sulforaphane on inflammation and dysregulation in Ca2+ homeostasis to determine if the individual compounds were working synergistically and/or through independent mechanisms. Rat hippocampal neurons or highly aggressive proliferating immortalized (HAPI) microglial cells were pre-treated for a week with either the individual components or all in combination before inducing Ca2+ buffering deficits with dopamine (DA, 0.1 µM for 2 h) or inflammation using lipopolysaccharide (LPS, 100 ng/mL for 18 h), respectively. The EGCG (3 µM) and combination protected against DA-induced deficits in Ca2+ buffering (both % of cells that recovered and recovery time, p < 0.05). Additionally, the EGCG and combination reduced stress-mediated inflammation in HAPI rat microglial cells by attenuating LPS-induced nitrite release, inducible nitrous oxide synthase (iNOS) expression, and tumor necrosis factor-alpha (TNF-α) release (p < 0.05), but not cyclooxygenase-2 (COX-2) expression. Overall, broccoli sprouts (2 µM) and curcumin (1 µM) were not as effective as the EGCG or combination. Further research is needed to determine if dietary intervention with a variety of foods containing compounds such as those found in green tea, turmeric, or broccoli sprouts can play a role in reducing age-related CNS inflammation, microglial activation, and downstream signaling pathways that can lead to neuronal dysfunction.

Topics: Animals; Anti-Inflammatory Agents; Catechin; Curcumin; Cyclooxygenase 2; Dopamine; Hippocampus; Inflammation; Isothiocyanates; Lipopolysaccharides; Microglia; Neurons; Nitrites; Nitrous Oxide; Phytochemicals; Rats; Tea; Tumor Necrosis Factor-alpha

Curcumin has been employed as a photosensitizer agent during photodynamic therapy (PDT). Cutibacterium acnes (C. acnes) can cause an inflammatory response in human keratinocytes; however, no research has been conducted to determine whether curcumin and its photodynamic properties can prevent this inflammatory reaction.. We hypothesized that curcumin may control the C. acnes biofilm-induced inflammatory response in keratinocytes, either alone or in combination with blue light photodynamic therapy.. Following C. acnes biofilm stimulation, human primary keratinocytes were treated with 20 μM curcumin solution alone or 5 μM curcumin with combined blue light irradiation. The amount of secreted protein was measured using an ELISA kit. The expression levels of Toll-like receptor 2 (TLR2) and its downstream proteins were determined using western blot.. Treatment with 20 μM curcumin, but not 5 μM curcumin, reduced the inflammatory response to C. acnes biofilms in keratinocytes by blocking the TLR2/MAPK/NF-κB pathway. Interestingly, 5 μM curcumin combined with blue light also reduced the C. acnes biofilm-induced inflammation indicated above by blocking the TLR2/MAPK/NF-κB pathway.. Curcumin alone, in sufficient concentrations, or low-concentration curcumin with blue light had anti-inflammatory activity on keratinocytes stimulated by C. acnes biofilms through inhibition of MAPK and NF-κB signaling pathways by downregulating TLR2 expression.

Topics: Curcumin; Humans; Inflammation; Keratinocytes; NF-kappa B; Photochemotherapy; Propionibacterium acnes

(1) Background: Exhaustive exercise can induce muscle damage. The consumption of nutritional compounds with the ability to positively influence the oxidative balance and an exacerbated inflammatory process has been previously studied. However, little is known about the nutritional value of curcumin (CCM) when mixed with whey protein concentrate (WPC). This study was developed to evaluate the effect of CCM-added WPC on inflammatory and oxidative process control and histopathological consequences in muscle tissue submitted to an exhaustive swimming test (ET). (2) Methods: 48 animals were randomly allocated to six groups (

Topics: Animals; Curcumin; Inflammation; Muscle, Skeletal; Oxidative Stress; Whey Proteins

Endurance running places substantial physiological strain on the body, which can develop into chronic inflammation and overuse injuries, negatively affecting subsequent training and performance. A recent study found that dietary polyphenols and methlysulfonylmethane (MSM) can reduce systemic inflammation and oxidative stress without adverse side effects.. The purpose was to identify a set of candidate protein and RNA biomarkers that are associated with improved outcomes related to inflammation and muscle injury, when athletes used 3 proprietary supplements both prior to and during early recovery from a half-marathon race.. The study was an open-label pilot study.. The study was field based, with sample analysis conducted in the Applied Physiology Laboratory in the Department of Kinesiology, Health Promotion and Recreation at the University of North Texas in Denton, Texas.. Participants were 15 young, exercise-trained men and women.. The intervention group consumed 1000 mg/d of a proprietary 50-50 mix of optimized curcumin and pomegranate extract for 26 days. The group also consumed 500 mg/d of a proprietary MSM for the same period. Three days prior to and one day after a race, the daily dosage was doubled. The control group received no supplements.. Venous blood samples were collected at pre-race and at 4h and 24h after running a half-marathon race. The research team evaluated results for target proteins that have been associated with inflammation and muscle injury in the scientific literature. The team also performed an analysis of RNA biomarkers.. At the 4h and 24h time points, a significant treatment-response was observed that included increases in proteins: (1) osteonectin/SPARC-osteonectin/secreted protein acidic and rich in cysteine and (2) BDNF-brain-derived neurotrophic factor. At the same points, the study also found increased RNA: (1) PACER-P50-associated COX-2 extragenic RNA, (2) PTGES-prostaglandin E synthase, (3) MYD88-innate immune signal transduction adaptor MYD88, (4) TNFS14-tumor necrosis factor (TNF) superfamily member 14, (5) THRIL-TNF and heterogeneous nuclear ribonucleoprotein L (HNRNPL)-related immunoregulatory long noncoding RNA, (6) TRAF6-TNF receptor associated factor 6, (7) CX3CL1-C-X3-C motif chemokine ligand 1, (8) MALAT1-metastasis-associated lung adenocarcinoma transcript 1, and (9) LINC00305-long intergenic nonprotein coding RNA 305.. The combination of polyphenol and MSM supplementation resulted in a systemic response that may translate to an accelerated rate of muscle recovery, allowing participants return to exercise and normal activities more quickly. This pilot study is the foundation for a larger investigation in the research team's laboratory.

Topics: Biomarkers; Curcumin; Dietary Supplements; Dimethyl Sulfoxide; Female; Homosexuality, Male; Humans; Inflammation; Male; Marathon Running; Myeloid Differentiation Factor 88; Osteonectin; Pilot Projects; Plant Extracts; Polyphenols; Pomegranate; RNA; Sexual and Gender Minorities; Sulfones; Systemic Inflammatory Response Syndrome

This work aimed to evaluate the effects of whey protein concentrate (WPC) admixtured of curcumin on metabolic control, inflammation and oxidative stress in Wistar rats submitted to exhaustive exercise. A total of forty-eight male rats were divided into six experimental groups (n 8): standard diet group (AIN-93M), standard diet submitted to exhaustion test group (AIN-93M ET), WPC admixtured of curcumin group (WPC + CCM), WPC + CCM submitted to exhaustion test group (WPC + CCM ET), CCM group and CCM subjected to exhaustion test group (CCM ET). The swimming exhaustion test was performed after 4 weeks of experiment. The consumption of WPC + CCM as well as isolated CCM did not alter the biometric measurements, the animals' food consumption and the hepatic and kidney function, as well as the protein balance of the animals (P > 0·05), but reduced the glycaemia and the gene expression of TNF-α and IL-6 and increased the expression of IL-10 (P < 0·05). The animals that were submitted to the exhaustion test (AIN-93M ET) showed higher aspartate aminotransferase values when compared to the animals that did not perform the exercise (AIN-93 M) (P < 0·05). WPC + CCM reduced the concentration of nitric oxide, carbonylated protein and increased the concentration of catalase (P < 0·05). Both (WPC + CCM and CCM) were able to increase the concentrations of superoxide dismutase (P < 0·05). We concluded that the WPC admixtured of CCM represents a strategy capable of decreasing blood glucose and oxidative and inflammatory damage caused by exhaustive physical exercise in swimming.

Topics: Animals; Curcumin; Inflammation; Male; Oxidative Stress; Rats; Rats, Wistar; Whey Proteins

Ulcerative colitis (UC) is an inflammatory bowel disease (IBD) characterized by diffuse inflammation of the colonic mucosa and a relapsing and remitting course. The current therapeutics are only modestly effective and carry risks for unacceptable adverse events, and thus more effective approaches to treat UC is clinically needed.. For this purpose, turmeric-derived nanoparticles with a specific population (TDNPs 2) were characterized, and their targeting ability and therapeutic effects against colitis were investigated systematically. The hydrodynamic size of TDNPs 2 was around 178 nm, and the zeta potential was negative (- 21.7 mV). Mass spectrometry identified TDNPs 2 containing high levels of lipids and proteins. Notably, curcumin, the bioactive constituent of turmeric, was evidenced in TDNPs 2. In lipopolysaccharide (LPS)-induced acute inflammation, TDNPs 2 showed excellent anti-inflammatory and antioxidant properties. In mice colitis models, we demonstrated that orally administrated of TDNPs 2 could ameliorate mice colitis and accelerate colitis resolution via regulating the expression of the pro-inflammatory cytokines, including TNF-α, IL-6, and IL-1β, and antioxidant gene, HO-1. Results obtained from transgenic mice with NF-κB-RE-Luc indicated that TDNPs 2-mediated inactivation of the NF-κB pathway might partially contribute to the protective effect of these particles against colitis.. Our results suggest that TDNPs 2 from edible turmeric represent a novel, natural colon-targeting therapeutics that may prevent colitis and promote wound repair in colitis while outperforming artificial nanoparticles in terms of low toxicity and ease of large-scale production.

Topics: Administration, Oral; Animals; Anti-Inflammatory Agents; Antioxidants; Colitis; Colitis, Ulcerative; Curcuma; Disease Models, Animal; Exosomes; Inflammation; Mice; Mice, Transgenic; NF-kappa B

Inflammation is caused by a cascade of events, one of which is the metabolism of arachidonic acid, that begins with oxidation by the enzyme 5-lipoxygenase. 5-Lipoxygenase (5-LOX) plays an important role in the inflammation process by synthesizing leukotrienes and several lipid mediators and has emerged as a possible therapeutic target for treatment of inflammatory diseases such as asthma and rheumatoid arthritis. Most of the existing 5-LOX inhibitors are synthetic and exhibit adverse side effects. In view of this, there is need to search for an alternate source of 5-LOX inhibitor with minimal side effects. The essential oil of several species of Curcuma has received considerable attention in recent times in traditional system of medicine especially for treating various inflammatory disorders. Therefore, the present study was carried out to screen the most potential 5-LOX inhibitors from essential oil components of Curcuma species and elucidate their mechanisms of action through computational biology approaches. Twenty-three phytoconstituents derived from the essential oil of Curcuma species were docked and their predictive binding energies were calculated to select the best possible ligand for 5-LOX. The top 8 ranked compounds from docking was tested for drug-likeness properties, bioactivity score, and toxicity analysis. The phytoconstituents such as α-turmerone, β-turmerone, α-terpineol and dihydrocarveolshowed the best binding affinity with 5-LOX and displayed favorable physicochemical properties. Molecular dynamics simulation in POPC lipid bilayers was carried out to understand the intrinsic dynamics and flexibility of the 5-LOX (apo) and 5-LOX-complex (α-terpineol, α-turmerone, β-turmerone and dihydrocarveol) systems. The molecular dynamic results showed that these 4 phytoconstituents interacted stably with the 5-LOX active site residues and the important bonds that were observed in the initial ligand docked compounds did not alter during the course of simulation. In general, our integrative computational approach demonstrated that the natural compounds like α-turmerone, β-turmerone, α-terpineol, and dihydrocarveol could be considered for designing specific anti-inflammatory drugs using structure-based drug design.

Topics: Arachidonate 5-Lipoxygenase; Curcuma; Inflammation; Ligands; Lipoxygenase Inhibitors; Molecular Docking Simulation; Molecular Dynamics Simulation; Oils, Volatile

Topics: Animals; Anti-Inflammatory Agents; Colitis; Colitis, Ulcerative; Colon; Curcuma; Cytokines; Dextran Sulfate; Disease Models, Animal; Gastrointestinal Microbiome; Inflammation; Mice; Mice, Inbred C57BL; Nanoparticle Drug Delivery System

This study aims to explore the effects of Garcinia mangostana (mangosteen) and Curcuma longa independently and synergistically in modulating induced inflammation and impaired brain neurotransmitters commonly observed in high-fat diet-induced obesity in rodent models. Male albino Wistar rats were divided into four experimental groups. Group I, control, obese, fed on a high-fat diet (HFD), and Group II-IV, fed on HFD then given mangosteen extract (400 mg/kg/day) and/or Curcuma (80 mg/kg/day), or a mixture of both for 6 weeks. Plasma pro-inflammatory cytokines, leptin, and brain serotonin, dopamine, and glutamate were measured in the five studied groups. G. mangostana and Curcuma longa extracts demonstrate antioxidant and DPPH radical scavenging activities. Both induced a significant reduction in the weight gained, concomitant with a non-significant decrease in the BMI (from 0.86 to 0.81 g/cm2). Curcuma either alone or in combination with MPE was more effective. Both extracts demonstrated anti-inflammatory effects and induced a significant reduction in levels of both IL-6 and IL-12. The lowest leptin level was achieved in the synergistically treated group, compared to independent treatments. Brain dopamine was the most affected variable, with significantly lower levels recorded in the Curcuma and synergistically treated groups than in the control group. Glutamate and serotonin levels were not affected significantly. The present study demonstrated that mangosteen pericarp extract (MPE) and Curcuma were independently and in combination effective in treating obesity-induced inflammation and demonstrating neuroprotective properties.

Topics: Animals; Brain; Curcuma; Diet, High-Fat; Dopamine; Garcinia mangostana; Glutamates; Inflammation; Leptin; Male; Neurotransmitter Agents; Obesity; Plant Extracts; Rats; Rats, Wistar; Serotonin

Obesity prevalence continues to increase and contribute to metabolic diseases, potentially by driving systemic inflammation. Curcumin is an anti-inflammatory spice with claimed health benefits. However, mechanisms by which curcumin may reduce obesity-associated inflammation are poorly understood; thus, it is hypothesized that benefits of curcumin consumption may occur through reduced white adipose tissue (WAT) inflammation and/or beneficial changes in gut bacteria.. Male B6 mice are fed high-fat diets (HFD, 45% kcal fat) or HFD supplemented with 0.4% (w/w) curcumin (HFC) for 14 weeks. Curcumin supplementation significantly reduces adiposity and total macrophage infiltration in WAT, compared to HFD group, consistent with reduced mRNA levels of M1 (Cd80, Cd38, Cd11c) and M2 (Arginase-1) macrophage markers. Moreover, curcumin supplementation reduces expression of other key pro-inflammatory genes, such as NF-κB p65 subunit (p65), Stat1, Tlr4, and Il6, in WAT (p < 0.05). Using microbial 16S RNA sequencing, it is demonstrated that the relative abundance of the Lactococcus, Parasutterella, and Turicibacter genera are increased in the HFC group versus HFD.. Curcumin exerts protective metabolic effects in dietary obesity, in part through downregulation of adipose tissue inflammation, which may be mediated by alterations in composition of gut microbiota, and metabolism of curcumin into curcumin-O-glucuronide.

Topics: Adipose Tissue; Adipose Tissue, White; Animals; Curcumin; Diet, High-Fat; Gastrointestinal Microbiome; Inflammation; Male; Mice; Mice, Inbred C57BL; Mice, Obese; Obesity

To investigate the pharmacodynamic mechanism of curcumin against myocardial ischaemia-reperfusion injury by regulating the phosphatidylinositol-3 kinase (PI3K)/protein kinase B (AKT)/rapamycin target protein (mTOR) signalling pathway.. The left anterior descending coronary artery was ligated for 30 min and reperfused for 3 h to establish an ischaemia-reperfusion injury model. The electrocardiogram (ECG) detection of rats was performed, and the degree of myocardial infarction was determined by 2,3,5-triphenyltetrazolium chloride staining. The expression levels of serum creatine kinase isoenzyme (CK), lactate dehydrogenase (LDH), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), malondialdehyde (MDA), nitric oxide (NO) and other related indicators were detected. The protein expressions of mTOR, phosphorylated (p)-mTOR, AKT and p-AKT were detected by Western blotting, whereas the expressions of Bcl-2 and Bax were detected by real-time polymerase chain reaction.. The results showed that compared with the model group, curcumin could improve the ECG findings, reduce the scope of myocardial infarction, reduce the expression levels of CK-MB, LDH, AST, MDA, NO and increase those of SOD and GSH. Curcumin can also down-regulate the expression of Bax and up-regulate the protein levels of Bcl2, p-mTOR and p-AKT (p < 0.05 or p < 0.01).. This study shows that curcumin has a significant protective effect on myocardial ischaemia-reperfusion, and its mechanism may be related to the activation of PI3K/AKT/mTOR signalling pathway and inhibition of inflammation, apoptosis and oxidative stress.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Apoptosis; Cell Line; Curcumin; Electrocardiography; Inflammation; Male; Myocardial Infarction; Myocardial Reperfusion Injury; Oxidative Stress; Phosphatidylinositol 3-Kinase; Proto-Oncogene Proteins c-akt; Rats; Rats, Sprague-Dawley; Signal Transduction; TOR Serine-Threonine Kinases

The present study was carried out to investigate the therapeutic effect of synthesized naturally compounds, curcumin nanoparticles (CurNPs) and metal oxide, zinc oxide nanoparticles (ZnONPs) on a high-fat diet (HFD)/streptozotocin (STZ)-induced hepatic and pancreatic pathophysiology in type 2 diabetes mellitus (T2DM) via measuring AKT pathway and MAPK pathway. T2DM rats were intraperitoneally injected with a low dose of 35 mg/kg STZ after being fed by HFD for 8 weeks. Then the rats have orally received treatments for 6 weeks. HFD/STZ-induced hepatic inflammation, reflected by increased phosphorylation of p38-MAPK pathway's molecules, was significantly decreased after nanoparticle supplementation. In addition, both nanoparticles significantly alleviated the decreased phosphorylation of AKT pathway. Further, administration of ZnONPs, CurNPs, conventional curcumin, and ZnSO

Topics: Animals; Antioxidants; Blood Glucose; Curcumin; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Diet, High-Fat; Hypoglycemic Agents; Inflammation; Insulin; Insulin Resistance; Liver; Male; Metformin; Nanoparticles; Obesity; Oxidative Stress; Rats; Streptozocin; Zinc Oxide

Sepsis is the leading condition associated with acute kidney injury (AKI) in the hospital and intensive care unit (ICU), sepsis-induced AKI (S-AKI) is strongly associated with poor clinical outcomes. Curcumin possesses an ability to ameliorate renal injury from ischemia-reperfusion, but it is still unknown whether they have the ability to reduce S-AKI. The aim of this study was to investigate the protective effects of curcumin on S-AKI and to assess its therapeutic potential on renal function, inflammatory response, and microcirculatory perfusion.. Male Sprague-Dawley (SD) rats underwent cecal ligation and puncture (CLP) to induce S-AKI and immediately received vehicle (CLP group) or curcumin (CLP+Cur group) after surgery. At 12 and 24h after surgery, serum indexes, inflammatory factors, cardiac output (CO), renal blood flow and microcirculatory flow were measured.. Serum levels of creatinine (Scr), cystatin C (CysC), IL-6 and TNF-α were significantly lower in the CLP+Cur group than those in the CLP group (P < 0.05). Treatment with curcumin improved renal microcirculation at 24h by measurement of contrast enhanced ultrasound (CEUS) quantitative parameters [peak intensity (PI); half of descending time (DT/2); area under curve (AUC); P < 0.05]. In histopathological analysis, treatment with curcumin reduced damage caused by CLP.. Curcumin can alleviate S-AKI in rats by improving renal microcirculatory perfusion and reducing inflammatory response. Curcumin may be a potential novel therapeutic agent for the prevention or reduction of S-AKI.

Topics: Acute Kidney Injury; Animals; Creatinine; Curcumin; Disease Models, Animal; Inflammation; Male; Microcirculation; Rats; Rats, Sprague-Dawley; Renal Circulation; Sepsis; Time Factors

Cell membrane vesicles (CMVs) are composed of natural cell membranes which makes them effective drug delivery systems with low immunogenicity and prolonged circulation time. However, targeting delivery of CMVs in vivo for clinical applications is still a major challenge. In this study, CXCR4 recombinant lentivirus is transfected into MC-3T3 cells and membrane CXCR4-enriched MC-3T3 cells are obtained. CMVs with enriched membrane CXCR4 display (CXCR4-CMVs) are obtained from the transfected MC-3T3 cells. Curcumin, an effective natural anti-inflammatory compound, is encapsulated into CXCR4-CMVs through physical entrapment (CXCR4/Cur-CMVs), with the membrane integrity of CXCR4/Cur-CMVs being well-preserved. CXCR4/Cur-CMVs induce enhanced M2 macrophage polarization, exhibit anti-inflammatory effects, and significantly improve homing via the CXCR4/CXCL12 axis in vitro. Utilizing ulcerative colitis and apical periodontitis as inflammatory disease models, it is found that CXCR4/Cur-CMVs are obviously aggregated within inflammatory areas after intravenous administration, which results in significant amelioration of ulcerative colitis and apical periodontitis. Therefore, this research may provide a feasible and innovative approach for fabricating an inflammatory site-targeting delivery system, by engineering CMVs to increase membrane-presenting CXCR4 receptor.

Topics: Animals; Cell Membrane; Curcumin; Disease Models, Animal; Drug Carriers; Inflammation; Male; Mice; Mice, Inbred BALB C; Receptors, CXCR4; Signal Transduction

Dietary polyphenols are potential anti-inflammatory agents, and their combinations with enhanced biological activities may lower toxicity and side effects. The objective of this work was to investigate the potential synergistic anti-inflammatory activities of apigenin and curcumin co-nanoencapsulated in sodium caseinate, with comparison to unencapsulated polyphenol combinations. Non-toxic concentrations of apigenin, curcumin, and their combinations in the free and co-encapsulated forms were studied in lipopolysaccharide-stimulated RAW 264.7 macrophage cells. Combinations of free polyphenols produced stronger inhibition of nitric oxide (NO) production, more significant at a higher proportion of curcumin, which was further enhanced after co-encapsulation. The enhanced reduction of NO was concomitant with the decreased expression of iNOS, the enhanced inhibition of pro-inflammatory cytokines of IL-6 and TNF-α, and the reduced production of intracellular reactive oxygen species. The potential multi-target effects and the enhanced solubility, proximity, and bioavailability of AP and CUR after co-encapsulation contributed to the synergistic activities. These results demonstrated that co-nanoencapsulation of apigenin and curcumin may enable the practical application utilizing the synergistic anti-inflammation effects to improve health.

Topics: Animals; Anti-Inflammatory Agents; Apigenin; Biological Availability; Caseins; Cell Survival; Curcumin; Cytokines; Inflammation; Interleukin-6; Lipopolysaccharides; Macrophages; Mice; Nitric Oxide; Particle Size; Polyphenols; RAW 264.7 Cells; Tumor Necrosis Factor-alpha

To fetch pathways involved in targetting Hsp90 through Curcumin and Epigallocatechin through Network pharmacological approach.. Hsp90 is a molecular chaperone involved in stabilizing inflammatory protein which may lead to chronic diseases. The herbal compounds Curcumin and Epigallocatechin processing antiinflammatory properties are known to follow a common pathway and control the expression of Hsp90.. To collect the gene targets of Hsp90, Curcumin and Epigallocatechin in order to understand protein-protein interactions of gene targets by constructing the interactome to identify the hub proteins. Hub proteins docking was performed with curcumin and epigallocatechin. Finally, hub proteins involvement with various human diseases were identified.. The gene targets of Hsp90, Curcumin and Epigallocatechin were obtained from there respective databases. Protein-protein interactions of Pkcδ-Nrf2 and Tlr4 pathway gene targets were collected from String database. Protein interaction network was constructed and merged to get intercession network in cytoscape and Cluego was used to predict the disease related target genes. Docking of ligands to target proteins was carried out using Autodock vina tool.. The main key regulators of Curcumin and Epigallocatechin were identified particularly from Pkcδ-Nrf2 and Tlr4 pathway.. The combined action of Curcumin and Epigallocatechin can reduce the expression of Hsp90 eventually controlling the inflammation.

Topics: Anti-Inflammatory Agents; Catechin; Curcumin; Drug Synergism; Flavonoids; HSP90 Heat-Shock Proteins; Humans; Inflammation; Molecular Chaperones; Molecular Docking Simulation; Network Pharmacology; NF-E2-Related Factor 2; Protein Interaction Mapping; Protein Kinase C-delta; Signal Transduction; Toll-Like Receptor 4

Endurance running training can lead to gradual accumulation of inflammation and soreness ultimately resulting in overuse injuries. Management of soreness and inflammation with pharmaceuticals (i.e. non-prescription pain relievers) during long-term training is not a suitable solution due to known side effects (e.g. gastrointestinal complications, etc.). Dietary polyphenols (i.e. curcumin, pomegranate, etc.) have been purported to reduce inflammation and muscle soreness, without these negative side effects making them ideal for use in an exercise model. The purpose of the present feasibility study was to explore the combined effect of optimized curcumin and pomegranate extract supplementation prior to (PRE) and after (4H and 24H) an organized half-marathon race on blood inflammatory proteins and inflammation-associated RNA. Daily supplementation (1000 mg/d) started 26 days before a half-marathon which doubled on days 27-31. Data were analyzed with R software and Welch t-test, significance set at

Topics: Antigens, CD; Curcumin; Dietary Supplements; Feasibility Studies; Humans; Inflammation; Mannose-Binding Lectin; Marathon Running; Muscle, Skeletal; Pomegranate; Receptors, Immunologic; Sports Nutritional Physiological Phenomena

Curcumin exhibits anti-inflammatory and antioxidant activities. We investigated the protective effects of curcumin in a renal injury rat model under dry-heat conditions. We divided Sprague-Dawley rats into four groups: dry-heat 0- (normal temperature control group), 50-, 100-, and 150-minute groups. Each group was divided into five subgroups (n = 10): normal saline (NS), sodium carboxymethylcellulose (CMCNa), and curcumin pretreated low, medium, and high-dose (50, 100, and 200 mg/kg, respectively) groups. Compared to the normal temperature group, serum creatinine, blood urea nitrogen, urinary kidney injury molecule-1, and neutrophil gelatinase-associated load changes in lipoprotein (NGAL) levels were significantly increased in the dry-heat environment group (P < .05); inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression and malondialdehyde (MDA) and related inflammatory factor levels were increased in the kidney tissue. Superoxide dismutase (SOD) and catalase (CAT) levels were decreased. However, following all curcumin pretreatment, the serum levels of kidney injury indicators and NGAL were decreased in the urine compared to those in the NS and CMCNa groups (P < .05), whereas renal SOD and CAT activities were increased and MDA was decreased (P < .05). Renal tissues of the 150-minute group showed obvious pathological changes. Compared to the NS group, pathological changes in the renal tissues of the 100- and 200-mg/kg curcumin groups were significantly reduced. Furthermore, iNOS and COX-2 expression and inflammatory factor levels were decreased after curcumin treatment. Curcumin exerted renoprotective effects that were likely mediated by its antioxidant and anti-inflammatory effects in a dry-heat environment rat model.

Topics: Acute Kidney Injury; Animals; Curcumin; Disease Models, Animal; Inflammation; Male; Oxidative Stress; Rats; Rats, Sprague-Dawley

Gingivitis can trigger gingival diseases such as periodontitis. Since the complete removal of microbial plaques by mechanical procedures is not conceivable in some conditions and also chemical mouthwashes have a lot of side effects, finding a new treatment strategy would be useful. In the present study, for the first time, the effects of oral nano-curcumin on gingival inflammation in patients with gingivitis and mild periodontitis were assessed. Forty eight patients with gingivitis and mild periodontitis participated in this clinical trial. In one group the patients were treated with Sina curcumin capsules 80 mg and the other group received a placebo. Clinical parameters, including modified gingival index, papillary bleeding index, and plaque index were determined on days 0, 7, 14, and 28. There were no significant differences in age, sex, papillary bleeding index (PBI), and modified gingival index (MGI) between the two groups at baseline. There was a dropout of two patients (both from the placebo group). The MGI and PBI have a significantly decreasing trend in both case and control groups and the decreases were severe in the case group. The differences between PBI and MGI in the two groups were significant at 14 and 28 days. The plaque index did not significantly change in either group over the study period. The trend of changes in plaque index was not different between the two groups of the study. In the current study, no side effect was found in the patients. Oral nano-curcumin has positive effects on the decrease of inflammation and gingival bleeding in patients with gingivitis and mild periodontitis. Nano-curcumin capsules have a systemic target site with more bioavailability than topical forms.

Topics: Capsules; Curcumin; Gingivitis; Humans; Inflammation; Periodontitis

The aim of the study was to evaluate the effect of systemically administrated curcumin on the prevention of peridural fibrotic tissue and adhesion formation in a rat laminectomy model.. Thirty-two Wistar albino rats were randomly selected and equally divided into 4 groups as follows: negative control group (group I) did not undergo operation; positive control group (group II) underwent laminectomy without treatment; group III (low-dose curcumin; 100 mg/kg); and group IV (high-dose curcumin; 200 mg/kg). Curcumin was administered intraperitoneally per day for 7 days after surgery starting from day 0. Twenty-eight days after surgery, T12 and L4 vertebral columns, paraspinal tissues, and epidural scar tissue were dissected en bloc and prepared for histopathologic examinations. All specimens were examined for inflammation, epidural fibrosis (EF), foreign body reaction, medulla spinalis retraction, granulation tissue, and arachnoid involvement. A Kruskal-Wallis test followed by a Dunn multiple comparison test were used for statistical analysis, and a P value <0.05 was considered as statistically significant.. Curcumin treatment significantly reduced inflammation, foreign body reaction, granulation tissue formation, medulla spinalis retraction, and EF formation compared with positive control group (P < 0.05); however, no significant differences were found between the 2 groups that received different doses of curcumin.. The results of the present study showed that systemic administration of curcumin was effective in reducing EF formation, inflammation, granulation tissue formation, medulla spinalis retraction, and foreign body reaction in the laminectomy area. Our results suggest that antiinflammatory activities of curcumin are beneficial for attenuation of EF formation.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Curcumin; Disease Models, Animal; Epidural Space; Female; Fibrosis; Foreign-Body Reaction; Inflammation; Laminectomy; Meninges; Rats; Rats, Wistar; Tissue Adhesions

Paclitaxel (PTX) is an antineoplastic agent commonly used in the treatment of solid tumors and is known to cause dose-limiting peripheral neurotoxicity. This study was performed to evaluate the protective effect of curcumin (CUR) against PTX-induced spinal cord and sciatic nerve injuries in rats. The rats were administered PTX (2 mg/kg, BW) intraperitoneally for the first 5 consecutive days followed by administration of CUR (100 and 200 mg/kg, BW daily in corn oil) orally for 10 days. Our results showed that CUR significantly reduced mRNA expression levels of NF-κB, TNF-α, IL-6, iNOS and GFAP whereas caused an increase in levels of Nrf2, HO-1 and NQO1 in the spinal cord and sciatic nerve of PTX-induced rats. In addition, CUR suppressed the activation of apoptotic and autophagic pathways by increasing Bcl-2 and Bcl-xL, and decreasing p53, caspase-3, Apaf-1, LC3A, LC3B and beclin-1 mRNA expression levels. The results showed that CUR also maintained the spinal cord and sciatic nerve histological architecture and integrity by both LFB staining and H&E staining. Immunohistochemical expressions of 8-OHdG, caspase-3 and LC3B in the PTX-induced spinal cord tissue were decreased after administration of CUR. Taken together, our findings demonstrated that CUR has protective effects on PTX-induced spinal cord and sciatic nerve injuries in rats.

Topics: Animals; Apoptosis; Autophagy; Curcumin; Inflammation; Male; Neuroprotective Agents; Paclitaxel; Rats, Sprague-Dawley; Sciatic Nerve; Sciatic Neuropathy; Spinal Cord; Spinal Cord Injuries

Topics: Catechin; COVID-19; Curcumin; Cytokines; Diet; Humans; Inflammation; Linoleic Acid; Nutritional Physiological Phenomena

The increase in drug-resistant strains of Staphylococcus aureus, especially methicillin-resistant S. aureus (MRSA), has led to an increased rate of infection-related mortality. The emergence of drug resistance has rendered many antibiotics ineffective. The poor penetration and retention of antibiotics in mammalian cells lead to recurrent latent infections. Thus, there is an increasing need for biodegradable, non-toxic anti-infectives that are effective in treating MRSA infections. Phytochemicals such as berberine (BBR) and curcumin (CCR) have long been explored for their antibacterial activities, but their efficacy is often limited due to low bioavailability, water solubility, and poor cell penetration. When used in combination these antimicrobials did not show any synergistic effect against MRSA. Here, both of them were co-encapsulated in liposomes (BCL) and evaluated for biocompatibility, synergistic antimicrobial activity, intracellular infections, associated inflammation, and on biofilms formed by MRSA. Co-encapsulation of BBR and CCR in liposomes decreased their MICs by 87% and 96%, respectively, as compared to their free forms with a FICI of 0.13, indicating synergy between them. BCL inhibited the growth of MRSA and prevented biofilm formation better than free drugs. Co-culture studies showed that intracellular infection was reduced to 77% post BCL treatment. It also reduced the production of pro-inflammatory cytokines by macrophages following infection. The liposomes were found to be five times more efficient than clindamycin and can be used as a potential antimicrobial carrier against intracellular infections.

Topics: Animals; Anti-Bacterial Agents; Berberine; Biofilms; Cells, Cultured; Curcumin; Humans; Inflammation; Liposomes; Methicillin-Resistant Staphylococcus aureus; Mice; Microbial Sensitivity Tests; Particle Size; Staphylococcal Infections; Surface Properties; THP-1 Cells

Aflatoxin B1 (AFB1) is a potent hepatotoxic and carcinogenic agent. Curcumin possesses potential anti-inflammatory, anti-oxidative and hepatoprotective effects. However, the role of LncRNAs in the protective mechanisms of curcumin against AFB1-induced liver damage is still elusive. Experimental broilers were randomly divided into 1) control group, 2) AFB1 group (1 mg/kg feed), 3) cur + AFB1 group (1 mg/kg AFB1 plus 300 mg/kg curcumin diet) and 4) curcumin group (300 mg/kg curcumin diet). Liver transcriptome analyses and qPCR were performed to identify shifts in genes expression. In addition, histopathological assessment and oxidant status were determined. Dietary AFB1 caused hepatic morphological injury, significantly increased the production of ROS, decreased liver antioxidant enzymes activities and induced inflammation and apoptosis. However, dietary curcumin partially attenuated the abnormal morphological changes, oxidative stress, and apoptosis in liver tissues. Transcriptional profiling results showed that 34 LncRNAs and 717 mRNAs were differentially expressed with AFB1 and curcumin co-treatment in livers of broilers. Analysis of the LncRNA-mRNA network, GO and KEGG enrichment data suggested that oxidative stress, inflammation and apoptosis pathway were crucial in curcumin's alleviating AFB1-induced liver damage. In conclusion, curcumin prevented AFB1-induced oxidative stress, inflammation and apoptosis through LncRNAs. These results provide new insights for unveiling the protective mechanisms of curcumin against AFB1-induced liver damage.

Topics: Aflatoxin B1; Animals; Antioxidants; Apoptosis; Chemical and Drug Induced Liver Injury, Chronic; Chickens; Curcumin; Diet; Inflammation; Liver; Oxidation-Reduction; Oxidative Stress; Protective Agents; RNA, Long Noncoding

Doxorubicin (DOX) chemotherapy is associated with the release of inflammatory cytokines from macrophages. This has been suggested to be, in part, due to DOX-mediated leakage of endotoxins from gut microflora, which activate Toll-like receptor 4 (TLR4) signaling in macrophages, causing severe inflammation. However, the direct function of DOX on macrophages is still unknown. In the present study, we tested the hypothesis that DOX alone is incapable of stimulating inflammatory response in macrophages. Then, we compared the anti-inflammatory effects of curcumin (CUR), resveratrol (RES) and sulforaphane (SFN) against lipopolysaccharide/interferon-gamma (LPS/IFN-γ)-mediated inflammation in the absence or presence of DOX. For this purpose, RAW 264.7 cells were stimulated with LPS/IFN-γ (10 ng/mL/10 U/mL) in the absence or presence of DOX (0.1 µM). Our results showed that DOX alone is incapable of stimulating an inflammatory response in RAW 264.7 macrophages. Furthermore, after 24 h of incubation with LPS/IFN-γ, a significant increase in tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and inducible nitric oxide synthase (iNOS) mRNA levels was observed. Similarly, nitric oxide (NO) production and TNF-α and IL-6 protein levels were significantly upregulated. Moreover, in LPS/IFN-γ-treated macrophages, the microRNAs (miRNAs) miR-146a, miR-155, and miR-21 were significantly overexpressed. Interestingly, upon testing CUR, RES, and SFN against LPS/IFN-γ-mediated inflammation, only SFN was able to significantly reverse the LPS/IFN-γ-mediated induction of iNOS, TNF-α and IL-6 and attenuate miR-146a and miR-155 levels. In conclusion, SFN, at the transcriptional and posttranscriptional levels, exhibits potent immunomodulatory action against LPS/IFN-γ-stimulated macrophages, which may indicate SFN as a potential treatment for DOX-associated inflammation.

Topics: Animals; Antibiotics, Antineoplastic; Curcumin; Doxorubicin; Immunologic Factors; Inflammation; Inflammation Mediators; Interferon-gamma; Interleukin-6; Isothiocyanates; Lipopolysaccharides; Macrophages; Mice; Molecular Targeted Therapy; Nitric Oxide Synthase Type II; RAW 264.7 Cells; Resveratrol; RNA, Messenger; Sulfoxides; Tumor Necrosis Factor-alpha

Trienones are curcuminoid analogues and are minor constituents in the rhizomes of numerous

Topics: Animals; Curcumin; Inflammation; Lipopolysaccharides; Lymphocyte Antigen 96; Macrophages; Mice; RAW 264.7 Cells; Transcription Factor RelA

Fine particulate matter (PM

Topics: Antioxidant Response Elements; Antioxidants; Apoptosis; Curcumin; Environmental Exposure; Humans; Inflammation; Interleukin-13; Interleukin-5; Lung Injury; NF-E2-Related Factor 2; Oxidative Stress; Particulate Matter; Reactive Oxygen Species

This study was intended to investigate the effect of Curcumin on acute pulmonary embolism (APE) via microRNA-21 (miR-21)/PTEN/NF-κB axis. APE model was induced on rats and administrated with Curcumin. Western blot analysis and RT-qPCR manifested the downregulation of Sp1, miR-21 and NF-κB, but the upregulation of PTEN in Curcumin-treated APE rats. Blood gas analysis, ELISA, and weighing of wet weight/dry weight (W/D) ratio indicated that Curcumin diminished mPAP and RVSP levels, W/D ratio, thrombus volume, and inflammatory factors in the lungs of APE rats. Further mechanical analysis was conducted by dual-luciferase reporter assays and ChIP assay, which showed that Sp1 increased miR-21 expression by binding to the miR-21 promoter, and that PTEN was targeted by miR-21. The APE rats were injected with adenovirus to evaluate the effect of Sp1, miR-21, or PTEN on lung injury and inflammation. It was observed that downregulation of miR-21 or Sp1, or upregulation of PTEN diminished mPAP and RVSP levels, W/D ratio, thrombus volume, and inflammatory factors in the lungs of APE rats. In summary, Curcumin decreased miR-21 expression by downregulating Sp1 to upregulate PTEN and to impair the NF-κB signaling pathway, thus suppressing lung injury and inflammation in APE rats.

Topics: Acute Lung Injury; Animals; Curcumin; Inflammation; MicroRNAs; NF-kappa B; PTEN Phosphohydrolase; Pulmonary Embolism; Rats; Rats, Sprague-Dawley; Signal Transduction

Topics: Animals; Curcumin; Gastrointestinal Motility; Humans; Inflammation; Interleukin-1beta; Intestinal Mucosa; Muscle, Smooth; Myosin-Light-Chain Kinase; NF-kappa B; Phosphorylation; Rats; Rats, Sprague-Dawley; Receptor, Cholecystokinin B; rhoA GTP-Binding Protein; Tumor Necrosis Factor-alpha

Inflammation plays a major role in the pathogenesis of acute lung injury (ALI), but the mechanism remains unclear. Current anti-inflammatory therapy has poor efficacy on ALI. The aim of this study was to investigate the protective mechanism of curcumin against ALI. In in vivo experiments, curcumin significantly alleviated lung inflammation, histopathological injury and MPO activity, serum concentrations of CCL7, IL-6 and TNF-α, and mortality in mice compared to the model group. RAW264.7 cells cultured in the presence of lipopolysaccharide and adenosine triphosphate showed significantly lower viability, higher pyroptotic percentage and inflammation, but supplement of curcumin increased the cell viability, reduced pyroptosis and inflammation. Additionally, the expressions of NF-κB and pyroptosis related proteins were notably increased, while Sirtuin 1 (SIRT1) was decreased in both in vivo and in vitro ALI models. The results suggested that curcumin remarkably inhibited the expression of NF-κB and pyroptosis related proteins and increased the expression of SIRT1. However, EX527, a SIRT1 inhibitor, blocked the protective effect of curcumin against ALI. In conclusion, curcumin has protective effect against ALI. It may inhibit inflammatory process by inhibiting the activation of NLRP3 inflammasome-dependent pyroptosis through the up-regulation of SIRT1.

Topics: Acute Lung Injury; Adenosine Triphosphate; Animals; Anti-Inflammatory Agents; Carbazoles; Curcumin; Disease Models, Animal; Inflammasomes; Inflammation; Lipopolysaccharides; Male; Mice; Mice, Inbred C57BL; NF-kappa B; NLR Family, Pyrin Domain-Containing 3 Protein; Pyroptosis; RAW 264.7 Cells; Sirtuin 1

Mesenchymal stem cells have an important potential in the treatment of age-related diseases. In the last years, small extracellular vesicles derived from these stem cells have been proposed as cell-free therapies. Cellular senescence and proinflammatory activation are involved in the loss of therapeutic capacity and in the phenomenon called inflamm-aging. The regulators of these two biological processes in mesenchymal stem cells are not well-known. In this study, we found that p65 is activated during cellular senescence and inflammatory activation in human umbilical cord-derived mesenchymal stem cell. To demonstrate the central role of p65 in these two processes, we used small-molecular inhibitors of p65, such as JSH-23, MG-132 and curcumin. We found that the inhibition of p65 prevents the cellular senescence phenotype in human umbilical cord-derived mesenchymal stem cells. Besides, p65 inhibition produced the inactivation of proinflammatory molecules as components of a senescence-associated secretory phenotype (SASP) (interleukin-6 and interleukin-8 (IL-6 and IL-8)). Additionally, we found that the inhibition of p65 prevents the transmission of paracrine senescence between mesenchymal stem cells and the proinflammatory message through small extracellular vesicles. Our work highlights the important role of p65 and its inhibition to restore the loss of functionality of small extracellular vesicles from senescent mesenchymal stem cells and their inflamm-aging signature.

Topics: Adolescent; Adult; Cell Proliferation; Cells, Cultured; Cellular Senescence; Curcumin; DNA Damage; Female; Humans; Inflammation; Leupeptins; Mesenchymal Stem Cells; Nanoparticles; Paracrine Communication; Phenotype; Phenylenediamines; Transcription Factor RelA; Umbilical Cord

Curcumin is a natural compound that has been widely used as a food additive and medicine in Asian countries. Over several decades, diverse biological effects of curcumin have been elucidated, such as anti-inflammatory and anti-oxidative activities. Monocyte chemoattractant protein-1 (MCP-1) is a key inflammatory marker during the development of atherosclerosis, and curcumin blocks MCP-1 expression stimulated by various ligands. Hence, we studied the action of curcumin on lysophosphatidic acid (LPA) mediated MCP-1 expression and explored the specific underlying mechanisms. In human vascular smooth muscle cells, LPA induces Rho-associated protein kinase (ROCK) dependent transforming growth factor receptor (TGFBR1) transactivation, leading to glycosaminoglycan chain elongation. We found that LPA also signals via the TGFBR1 transactivation pathway to regulate MCP-1 expression. Curcumin blocks LPA mediated TGFBR1 transactivation and subsequent MCP-1 expression by blocking the ROCK signalling. In the vasculature, ROCK signalling regulates smooth muscle cell contraction, inflammatory cell recruitment, endothelial dysfunction and vascular remodelling. Therefore, curcumin as a ROCK signalling inhibitor has the potential to prevent atherogenesis via multiple ways.

Topics: Animals; Blotting, Western; Cell Line; Cell Survival; Chemokine CCL2; Curcumin; Humans; Inflammation; Lysophospholipids; Muscle, Smooth, Vascular; Receptors, Transforming Growth Factor beta; rho-Associated Kinases; Signal Transduction

Cerebral ischemic injury is one of the debilitating diseases showing that inflammation plays an important role in worsening ischemic damage. Therefore, studying the effects of some potential anti-inflammatory compounds can be very important in the treatment of cerebral ischemic injury.. This study investigated anti-inflammatory effects of triblock copolymer nanomicelles loaded with curcumin (abbreviated as NC) in the brain of rats following transient cerebral ischemia/reperfusion (I/R) injury in stroke. After preparation of NC, their protective effects against bilateral common carotid artery occlusion (BCCAO) were explored by different techniques. Concentrations of free curcumin (C) and NC in liver, kidney, brain, and heart organs, as well as in plasma, were measured using a spectrofluorometer. Western blot analysis was then used to measure NF-κB-p65 protein expression levels. Also, ELISA assay was used to examine the level of cytokines IL-1β, IL-6, and TNF-α. Lipid peroxidation levels were assessed using MDA assay and H&E staining was used for histopathological examination of the hippocampus tissue sections.. The results showed a higher level of NC compared to C in plasma and organs including the brain, heart, and kidneys. Significant upregulation of NF-κB, IL-1β, IL-6, and TNF-α expressions compared to control was observed in rats after induction of I/R, which leads to an increase in inflammation. However, NC was able to downregulate significantly the level of these inflammatory cytokines compared to C. Also, the level of lipid peroxidation in pre-treated rats with 80mg/kg NC was significantly reduced.. Our findings in the current study demonstrate a therapeutic effect of NC in an animal model of cerebral ischemia/reperfusion (I/R) injury in stroke through the downregulation of NF-κB-p65 protein and inflammatory cytokines.

Topics: Animals; Anti-Inflammatory Agents; Brain; Brain Ischemia; Curcumin; Cytokines; Disease Models, Animal; Down-Regulation; Inflammation; Lactates; Lipid Peroxidation; Male; Malondialdehyde; Micelles; Nanoparticles; NF-kappa B; Phosphorylation; Polyethylene Glycols; Polymers; Rats, Wistar; Signal Transduction; Tissue Distribution; Transcription Factor RelA

Alzheimer's disease (AD) is one of the most common neurodegenerative diseases leading to dementia. Despite research efforts, currently there are no effective pharmacotherapeutic options for the prevention and treatment of AD. Recently, numerous studies highlighted the beneficial effects of curcumin (CUR), a natural polyphenol, in the neuroprotection. Especially, its dual antioxidant and anti-inflammatory properties attracted the interest of researchers. In fact, besides its antioxidant and anti-inflammatory properties, this biomolecule is not degraded in the intestinal tract. Additionally, CUR is able to cross the blood-brain barrier and could therefore to be used to treat neurodegenerative pathologies associated with oxidative stress, inflammation and apoptosis. The present study aimed to assess the ability of CUR to induce neuronal protective and/or recovery effects on a rat model of neurotoxicity induced by aluminum chloride (AlCl

Topics: Acetylcholinesterase; Aluminum Chloride; Alzheimer Disease; Animals; Anxiety; Apoptosis; Body Weight; Cell Survival; Cognitive Dysfunction; Curcumin; Cytokines; Disease Models, Animal; Hippocampus; Inflammation; Inflammation Mediators; Male; Nerve Degeneration; Neuroprotective Agents; Neurotoxicity Syndromes; Organ Size; Oxidative Stress; Rats, Wistar

The purpose of this pilot study was to evaluate and determine the concentration of prostaglandin GF2α (PGF2α) and isoprostane 8-iso-PGF2α in plasma and intestine of specific pathogen-free (SPF) Leghorn chickens challenged with Eimeria maxima, with or without dietary supplementation of curcumin using solid-phase microextraction and ultra-performance liquid chromatography/tandem mass spectrometry. Eighty 1-day-old male SPF chickens were randomly allocated to one of four groups with four replicates (n = 5 chickens/replicate). Groups consisted of: (1) Control (no challenge), (2) Curcumin (no challenge), (3) Eimeria maxima (challenge), and (4) Eimeria maxima (challenge) + curcumin. At day 28 of age, all chickens in the challenge groups were orally gavaged with 40,000 sporulated E. maxima oocysts. No significant differences (P > 0.05) were observed in the groups regardless of the treatment or challenge with E. maxima. Enteric levels of both isoprostane 8-iso-PGF2α and PGF2α at 7 days and 9 days post-challenge were significantly increased (P < 0.01) compared to the non-challenge control chickens. Interestingly, the enteric levels of both isoprostane 8-iso-PGF2α and PGF2α at 7 days post-challenge were significantly reduced in chickens fed curcumin, compared to control chickens challenge with E. maxima. At 9 days post-challenge, only levels of isoprostane 8-iso-PGF2α in the enteric samples were significantly reduced in chickens challenged with E. maxima supplemented with curcumin, compared with E. maxima challenge chickens. No differences of isoprostane 8-iso-PGF2α or PGF2α were observed in plasma at both days of evaluation. Similarly, no significant differences were observed between the challenge control or chickens challenge with E. maxima and supplemented with curcumin at both times of evaluation. The results of this pilot study suggests that the antioxidant anti-inflammatory properties of curcumin reduced the oxidative damage and subsequent intestinal mucosal over-production of lipid oxidation products. Further studies to confirm and extend these results in broiler chickens are required.

Topics: Animal Feed; Animals; Animals, Newborn; Anti-Inflammatory Agents; Chickens; Coccidiosis; Curcumin; Dietary Supplements; Dinoprost; Eimeria; Inflammation; Intestinal Mucosa; Male; Oocysts; Oxidative Stress; Poultry Diseases; Specific Pathogen-Free Organisms

Dietary factors can reshape the gut microbiota and consequently affect disease progression. We previously reported that tetrahydrocurcumin (THC), the major active metabolite of curcumin (Cur), could ameliorate allergic inflammation in asthmatic mice. Herein, we aimed to investigate whether THC or Cur exerts anti-inflammatory effects on allergic asthma via modulating gut microbiota. Ovalbumin (OVA)-induced asthmatic mice were treated with Cur or THC, and the gut microbiota profiles were analyzed by 16S rRNA sequencing. Fecal microbiota transplantation (FMT) from Cur- or THC-fed donor mice was administered to OVA-induced asthmatic mice. Nasal symptoms and inflammation patterns of lungs and colons were evaluated in control, OVA-induced and Cur-or THC-treated mice. Both Cur and THC treatment could alter the compositions of the gut microbiota in asthmatic mice, characterized by a significant decrease in the ratio of Firmicutes to Bacteroidetes; Cur or THC supplementation also reduced the relative abundances of pro-inflammatory bacteria, e.g., Proteobacteria, Intestinimonas, Unidentified-Ruminococcaceae, and Lachnospiraceae, in OVA-induced mice. The relative abundances of Unidentified-Ruminococcaceae, Romboutsia, Intestinimonas, Akkermansia, and Mucispirillum were positively associated with the levels of Th2-related factors in asthmatic mice upon Cur or THC treatment. Moreover, THC-FMT showed better preventive effects than Cur-FMT on the development of allergic inflammation in OVA-induced mice, resulting in a reduction in symptoms and Th2-mediated inflammation in both lung and colon tissues. The results reveal that Cur- or THC-mediated alleviation of airway allergic inflammation is dependent on gut microbiota modulation. THC-induced gut microbiota may have therapeutic potential for asthma treatment.

Topics: Animals; Asthma; Curcumin; Female; Gastrointestinal Microbiome; Inflammation; Lung; Mice; Mice, Inbred BALB C

Ammonia is one of the most major pollutant and stress factors of aquaculture systems, and has seriously endangered fish health. However, few studies have been performed on mechanisms of the detrimental impact of ammonia stress and mitigation in fish. A study was carried out to investigate the response of genes involved in inflammation, antioxidation, polarization and apoptosis in head kidney macrophages to acute ammonia toxicity, and the alleviation effect of curcumin. The cells were divided into six groups, as follows: The control group composed of untreated macrophages (CON), the experimental groups, consisting of macrophages treated with 0.23 mg L

Topics: Ammonia; Animals; Anti-Inflammatory Agents, Non-Steroidal; Apoptosis; Catfishes; Curcumin; Gene Expression Regulation; Head Kidney; Humans; Inflammation; Macrophages; Oxidative Stress; RNA, Messenger

Topics: Acute Kidney Injury; Animals; Apoptosis; Blood Urea Nitrogen; Curcumin; Cytokines; Inflammation; Kidney; Male; Mice; Mice, Inbred C57BL; Oxidative Stress; Protective Agents; Sepsis; Signal Transduction; Sirtuin 1

Obesity can induce chronic low-grade inflammation via oxidative stress. Tetrahydrocurcumin (THC) is a major curcumin metabolite with anti-inflammatory and antioxidant effects, but little is known about its effects on the skin of obese individuals. Thus, the aim of this study was to investigate the effects of THC on inflammatory cytokine production, oxidative stress, and autophagy in the skin of mice with high-fat diet- (HFD-) induced obesity. Eight-week-old C57BL/6J mice were fed a regular diet, HFD (60% of total calories from fat), or HFD supplemented with THC (100 mg/kg/day orally) for 12 weeks. We measured their body weights during the experimental period. After 12-week treatments, we performed western blotting and real-time polymerase chain reaction analyses on skin samples to evaluate the expression of inflammatory cytokines, oxidative stress markers, and autophagy markers. We observed higher tumor necrosis factor-

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Autophagy; Body Weight; Curcumin; Cytokines; Diet, High-Fat; Inflammation; Male; Mice; Mice, Inbred C57BL; Mice, Obese; Obesity; Oxidative Stress; Signal Transduction; Skin; Skin Diseases; Temperature

Human dental pulp stem cells (hDPSCs) have significant potential of immunomodulatory for therapeutic and regenerative biomedical applications compared to other mesenchymal stem cells (MSCs). Nowadays, alteration of gene expression is an important way to improve the performance of MSCs in the clinic. MicroRNAs (miRs) and CD200 are known to modulate the immune system in MSCs. Curcumin is famous for its anti-inflammatory impacts. Phytosomal curcumin (PC) is a nanoparticle synthesized from curcumin that removes the drawbacks of curcumin. The purpose of this research was to assess the effects of PC on the expression of the CD200 and four key miRNAs in immune system. PC (30 μM) treatment of hDPSCs could ameliorate their immunoregulatory property, presented by reduced expressions of miR-21, miR-155 and miR-126, as well as enhanced expressions of miR-23 and CD200. The PC was also able to reduce PI3K\\AKT1\\NF-κB expressions that were target genes for these miRs and involved in inflammatory pathways. Moreover, PC was more effective than curcumin in improving the immune modulation of hDPSCs. Evidence in this study suggested that PC mediates immunoregulatory activities in hDPSC via miRs and CD200 to regulate PI3K\\AKT1\\NF-κB signalling pathways, which may provide a theoretical basis for PC in the treatment of many diseases. SIGNIFICANCE OF THE STUDY: Autoimmune diseases or tooth caries are partly attributed to global health problems and their common drug treatments have several side effects. The goal of this study is dentin regeneration and autoimmune diseases treatment via stem cell-based approaches with phytosomal curcumin (PC), for the first time. Because dental pulp stem cells have unique advantages (including higher immunomodulatory capacity) over other mesenchymal stem cells, we considered them the best option for treating these diseases. Using PC, we try to increase the immunomodulatory properties of these cells.

Topics: Antigens, CD; Cells, Cultured; Curcumin; Dental Pulp; Humans; Inflammation; MicroRNAs; Nanoparticles; Stem Cells

Topics: Anti-Inflammatory Agents, Non-Steroidal; Cell Differentiation; Curcumin; Endothelium, Vascular; Humans; Inflammation; Lipopolysaccharides; Liposomes; Neural Crest; Periodontal Ligament; Porphyromonas gingivalis; Reactive Oxygen Species; Stem Cells

Topics: Apoptosis; Cartilage; Cells, Cultured; Chondrocytes; Curcuma; Curcumin; Cyclooxygenase 2; Humans; I-kappa B Kinase; Imidazoles; Inflammation; Interleukin-1beta; NF-kappa B; Osteoarthritis; Primary Cell Culture; Quinoxalines; Signal Transduction; SOX9 Transcription Factor; Tumor Necrosis Factor-alpha

Topics: Animals; Apolipoproteins E; Atherosclerosis; Chronic Disease; Curcumin; Immunomodulating Agents; Inflammation; Interleukin-10; Lipids; Mice; Mice, Inbred C57BL; Neuroprotection

Sodium alginate products have been extensively used for wound-dressing. In present study, a series of thermo-sensitive cross-linked poly(N-isopropylacrylamide) grafted sodium alginate (Alg-g-pNIPAM) copolymers were synthesized for delivery of curcumin to wound. FTIR,

Topics: Acrylic Resins; Alginates; Animals; Anti-Inflammatory Agents; Bandages; Curcumin; Drug Carriers; Drug Liberation; Female; Hydrogels; Inflammation; Rats; Skin; Soft Tissue Injuries; Viscosity; Wound Healing

Telocytes (TCs) are a distinct type of interstitial cells that play a vital role in the pathogenesis of ulcerative colitis and colonic tissue hemostasis. The aim of this study was to examine the effect of nanocurcumin (NC) on the morphometric and immunohistochemical characterization of TCs in the ulcerative colitis (UC) rat model.. Forty rats were randomly divided into control, NC, UC, and UC+NC groups. At the end of the experiment, the colon was dissected and prepared for histopathological and immunohistochemical assessment. Tissue homogenates were prepared for real-time PCR assessment of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-. NC successfully targeted the colonic tissue, improved the mucosal lesion, preserve TCs distribution, and count through its anti-inflammatory and fibrinolytic properties.

Topics: Animals; Colitis; Colitis, Ulcerative; Colon; Curcumin; Disease Models, Animal; Fibrinolysis; Gene Expression Regulation; Immunohistochemistry; Inflammation; Interleukin-6; Intestinal Mucosa; Male; Nanoparticles; Rats; Rats, Wistar; Spectroscopy, Fourier Transform Infrared; Telocytes; Transforming Growth Factor beta1; Tumor Necrosis Factor-alpha; Vimentin

Reusing deep-fried vegetable oils multiple times is a common practice to save costs, and their chronic consumption may cause hepatic dysfunction. In this investigation, we assessed the modulatory effects of ginger and turmeric lipid-solubles that may migrate to oils during heating on the hepatic inflammatory response in rats.. Male Wistar rats were fed with; 1) control {native canola (N-CNO) or native sunflower (N-SFO)} oil, 2) heated (heated canola {(H-CNO) or heated sunflower (H-SFO)} oil, and 3) heated oil with ginger or turmeric {heated canola with ginger (H-CNO + GI) or heated canola oil with turmeric (H-CNO + TU), heated sunflower oil with ginger (H-SFO + GI) or heated sunflower oil with turmeric (H-SFO + TU)} for 120 days. Hepatic inflammatory response comprising eicosanoids, cytokines, and NF-kB were assessed.. Compared to respective controls, feeding heated oils significantly (p < 0.05); 1) increased eicosanoids (PGE. Consumption of repeatedly heated oil may cause hepatic dysfunction by inducing inflammatory stress through NF-kB upregulation. Lipid-solubles from ginger and turmeric that may migrate to oil during heating prevent the hepatic inflammatory response triggered by heated oils in rats.

Topics: Animals; Curcuma; Cytokines; Down-Regulation; Eicosanoids; Hot Temperature; Inflammation; Lipids; Liver Diseases; Male; NF-kappa B; Rapeseed Oil; Rats; Rats, Wistar; Sunflower Oil; Zingiber officinale

Curcuma longa L is traditionally used as an anti-inflammatory remedy in Chinese traditional medicine. Curcuma oil (CO), a lipophilic fraction from Curcuma longa L. has been reported to have anti-proliferative, anti-inflammatory and anti-oxidant activities. However, CO has never been investigated for its possible therapeutic effects on benign prostatic hyperplasia (BPH).. The study is thus to determine the therapeutic effects of curcuma oil on BPH and also the possible mechanism (s) of action.. A BPH-1 cell line and Sprague Dawley (SD) rats were used to establish BPH models in vitro and in vivo, respectively. Rats were treated by CO (2.4, 7.2 mg/kg/i.g.) and finasteride (5 mg/kg/i.g.), respectively. Histological changes were examined by hematoxylin and eosin (H&E) staining. Protein expression was analyzed for 5α-reductase (5AR), dihydrotestosterone (DHT), interleukin (IL)-1β, IL-6 and tumor necrosis factor (TNF)-α by ELISA. Ki-67, Caspase-8,-9 and -3 expressions were evaluated via immunohistochemistry (IHC).. CO effectively induced apoptosis in BPH-1 cells. BPH was successfully established by administration of testosterone propionate (TP) in rats, which upregulated both 5α-reductase expression and DHT production. Importantly, TP establishment significantly stimulated the phosphorylation of p65, one subunit of NF-κB, thus led to activation of the NF-κB signaling pathway in prostatic tissues of rats. In turn, the activation of NF-κB pathway induced concomitant upregulation of proinflammatory factors IL-1β, IL-6, TNF-α, and COX-2 and significant increase of the Bcl2/Bax expression ratio for enhanced cell survival, contributing to the initiation and progression of BPH in rats. Notably, CO therapy significantly decreased prostate weight and hyperplasia in BPH-induced animals. Also CO was found to suppress the expression of 5α-reductase and thus the production of DHT, which is essential for the amelioration of BPH. More importantly, CO was shown to suppress the activation of NF-κB pathway through decreasing the expression of phosphorylated p65 and consequently reduced the inflammatory responses and cell survival in prostatic tissues, leading to the inhibition of BPH development in rats.. Curcuma oil is very effective for ameliorating BPH in rats. The underlying mechanisms involve in reduced inflammatory responses and cell survival through suppression of the NF-κB signaling pathway by CO in prostatic tissues.

Topics: Animals; Cell Line; Cell Survival; Curcuma; Disease Models, Animal; Disease Progression; Humans; Inflammation; Male; NF-kappa B; Plant Oils; Prostatic Hyperplasia; Rats; Rats, Sprague-Dawley; Signal Transduction

Eight new flavonoids, including two β-hydroxy/methoxychalcones, velutones A and B (

Topics: Animals; Caspase 1; Flavonoids; Humans; Inflammasomes; Inflammation; Lipopolysaccharides; Macrophages; Mice; Millettia; Molecular Structure; NLR Family, Pyrin Domain-Containing 3 Protein; THP-1 Cells

Diclofenac (DCL), an anti-inflammatory drug used to reduce pain and inflammation, ranks in the top causes of drug-induced liver injury. The inflammatory stress induced by inflammagens is implicated in DCL-induced liver injury. Curcumin (CUR) and selenium (Se) possess anti-inflammatory effects; therefore, this study evaluated their protective potential against lipopolysaccharide (LPS)/DCL-induced liver injury. Rats received CUR and/or Se for 7 days followed by a single intravenous administration of LPS 2 h before a single injection of DCL and two other doses of CUR and/or Se 2 and 8 h after DCL. Administration of nontoxic doses of LPS and DCL resulted in liver damage evidenced by the significantly elevated liver function markers in serum. LPS/DCL-induced liver injury was confirmed by histological alterations, increased lipid peroxidation and nitric oxide, and diminished glutathione and superoxide dismutase. CUR and/or Se prevented liver injury, histological alterations, and oxidative stress and boosted antioxidant defenses in LPS/DCL-induced rats. In addition, CUR and/or Se reduced serum C-reactive protein, liver pro-inflammatory cytokines, and the expression of TLR4, NF-κB, JNK, and p38, and upregulated heme oxygenase-1 (HO-1). In conclusion, CUR and/or Se mitigated LPS/DCL-induced liver injury in rats by suppressing TLR4 signaling, inflammation, and oxidative stress and boosting HO-1 and other antioxidants. Therefore, CUR and Se can hinder the progression and severity of liver injury during acute inflammatory episodes.

Topics: Animals; Biomarkers; Chemical and Drug Induced Liver Injury, Chronic; Curcumin; Diclofenac; Inflammation; Injections, Intravenous; Lipopolysaccharides; Male; Oxidative Stress; Rats; Rats, Wistar; Selenium

Oxaliplatin is a first-line clinical drug in cancer treatment and its side effects of peripheral neuropathic pain have also attracted much attention. Neuroinflammation induced by oxidative stress-mediated activation of nuclear factor-kappa B (NF-κB) plays an important role in the course. Current studies have shown that curcumin has various biological activities like antioxidant, anti-inflammatory, antitumor and so on, while few studies were conducted about its role in oxaliplatin-induced peripheral neuropathic pain. The aim of this study is to verify the mechanism of curcumin alleviating oxaliplatin-induced peripheral neuropathic pain. Intraperitoneal injection with oxaliplatin (4 mg/kg body weight) was given to the rats twice a week and last for four weeks to establish the model rats. Gavage administration of curcumin (12.5, 25, and 50 mg/kg body weight, respectively) was conducted for consecutive 28 d to explore the effects and potential mechanism. Our results showed that curcumin administration could increase mechanical withdrawal threshold and decrease the paw-withdrawal times of cold allodynia significantly; meanwhile, motor nerve conduction velocity (MNCV) and sense nerve conduction velocity (SNCV) were both increased and the injured neurons of the spinal cord were repaired. In addition, curcumin administration increased superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT) and reduced malondialdehyde (MDA). Moreover, the curcumin operation inhibited the activated of NF-κB and level of inflammatory factors like tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6). In conclusion, these findings suggested that curcumin could alleviate oxaliplatin-induced peripheral neuropathic pain; the mechanism might be inhibiting oxidative stress-mediated activation of NF-κB and mitigating neuroinflammation.

Topics: Animals; Antioxidants; Catalase; Curcumin; Glutathione Peroxidase; Hyperalgesia; Inflammation; Interleukin-1beta; Interleukin-6; Male; Malondialdehyde; Neural Conduction; Neuralgia; NF-kappa B; Oxaliplatin; Oxidative Stress; Rats; Rats, Sprague-Dawley; Spinal Cord; Superoxide Dismutase; Tumor Necrosis Factor-alpha

Topics: A549 Cells; Alveolar Epithelial Cells; Animals; Anti-Inflammatory Agents, Non-Steroidal; Bronchoalveolar Lavage Fluid; Curcumin; Humans; Hypoxia; Hypoxia-Inducible Factor 1, alpha Subunit; Inflammation; Male; NF-kappa B; Pulmonary Alveoli; Rats; Rats, Sprague-Dawley; Signal Transduction; Tight Junction Proteins

The development of obesity-associated complications is related to various pathogenic events including chronic inflammation, oxidative stress and generation of advanced glycation end products (AGEs). Due to their antioxidant, anti-inflammatory and antiglycation properties, trigonelline and curcumin are interesting candidates to counteract complications of obesity and diabetes mellitus. The current study aimed to investigate the effects of treatment with curcumin or trigonelline mixed into yoghurt, alone or in combination, on mice fed high-fat diet (HFD); the focus was mainly on the potential of these phytochemicals to counteract oxidative and glycative stress. Yoghurt alone improved glucose tolerance and reduced proinflammatory cytokine levels in HFD mice; however, it did not affect the antioxidant status. Trigonelline-enriched yoghurt prevented fat accumulation in adipose tissue, improved both insulin sensitivity and glucose tolerance and exerted anti-inflammatory and antiglycation activities (reduced AGEs and AGE receptor levels and increased the levels of components related to AGE detoxification) in liver and kidney of HFD mice. Curcumin-enriched yoghurt exerted anti-inflammatory and potent antioxidant properties (increased antioxidant enzyme activities and decreased lipid peroxidation) in liver and kidney of HFD mice. However, several beneficial effects were nullified when trigonelline and curcumin were administered in combination. Trigonelline and curcumin have emerged as promising complementary therapy candidates for liver and kidney complications associated with obesity. However, the administration of these phytochemicals in combination, at least in HFD mice, was not effective; inhibition of biotransformation processes and/or the reaching of toxic doses during combined treatment may be prevailing over the individual pharmacodynamic actions of these phytochemicals.

Topics: Alkaloids; Animals; Antioxidants; Biomarkers; Blood Glucose; Body Weight; Curcumin; Diet, High-Fat; Disease Models, Animal; Drug Therapy, Combination; Glucose; Glucose Tolerance Test; Glycosylation; Homeostasis; Inflammation; Kidney; Lipid Peroxidation; Liver; Male; Mice; Mice, Inbred C57BL; Obesity; Oxidative Stress

Herpes Simplex Virus Type 2 (HSV-2) is one of the most prevalent sexually transmitted viruses and is a known risk factor for HIV acquisition in the Female Genital Tract (FGT). Previously, we found that curcumin can block HSV-2 infection and abrogate the production of inflammatory cytokines and chemokines by genital epithelial cells in vitro. In this study, we investigated whether curcumin, encapsulated in nanoparticles and delivered by various in vivo routes, could minimize inflammation and prevent or reduce HSV-2 infection in the FGT. Female mice were pre-treated with curcumin nanoparticles through oral, intraperitoneal and intravaginal routes, and then exposed intravaginally to the tissue inflammation stimulant CpG-oligodeoxynucleotide (ODN). Local intravaginal delivery of curcumin nanoparticles, but not intraperitoneal or oral delivery, reduced CpG-mediated inflammatory histopathology and decreased production of pro-inflammatory cytokines Interleukin (IL)-6, Tumor Necrosis Factor Alpha (TNF-α) and Monocyte Chemoattractant Protein-1 (MCP-1) in the FGT. However, curcumin nanoparticles did not demonstrate anti-viral activity nor reduce tissue pathology when administered prior to intravaginal HSV-2 infection. In an alternative approach, intravaginal pre-treatment with crude curcumin or solid dispersion formulations of curcumin demonstrated increased survival and delayed pathology following HSV-2 infection. Our results suggest that curcumin nanoparticle delivery in the vaginal tract could reduce local tissue inflammation. The anti-inflammatory properties of curcumin delivered to the vaginal tract could potentially reduce the severity of HSV-2 infection and decrease the risk of HIV acquisition in the FGT of women.

Topics: Administration, Intravaginal; Animals; Chemokine CCL2; Curcumin; Drug Carriers; Epithelial Cells; Female; Genitalia, Female; Herpes Simplex; Herpesvirus 2, Human; Humans; Inflammation; Interleukin-6; Mice; Mice, Inbred C57BL; Nanoparticles; Oligodeoxyribonucleotides; Severity of Illness Index; Tumor Necrosis Factor-alpha; Vagina

Colorectal cancer (CRC) is the second leading cause of cancer death worldwide. Therefore, it is important to establish useful methods for preventing CRC. One prevention strategy involves the use of cancer chemopreventive agents, including functional foods. We focused on the well-known cancer chemopreventive agent curcumin, which is derived from turmeric. However, curcumin has the disadvantage of being poorly soluble in water due to its high hydrophobicity. To overcome this problem, the formation of submicron particles with surface controlled technology has been applied to curcumin to give it remarkably improved water solubility, and this derived compound is named Theracurmin. To date, the preventive effects of Theracurmin on hereditary intestinal carcinogenesis have not been elucidated. Thus, we used Apc-mutant mice, a model of familial adenomatous polyposis, to evaluate the effects of Theracurmin. First, we showed that treatment with 10-20 µM Theracurmin for 24 hours reduced nuclear factor-κB (NF-κB) transcriptional activity in human colon cancer DLD-1 and HCT116 cells. However, treatment with curcumin mixed in water did not change the NF-κB promoter transcriptional activity. As NF-κB is a regulator of inflammation-related factors, we next investigated the downstream targets of NF-κB: monocyte chemoattractant protein-1 (MCP-1) and interleukin (IL)-6. We found that treatment with 500 ppm Theracurmin for 8 weeks inhibited intestinal polyp development and suppressed MCP-1 and IL-6 mRNA expression levels in the parts of the intestine with polyps. This report provides a proof of concept for the ongoing Theracurmin human trial (J-CAP-C study).

Topics: Adenomatous Polyposis Coli; Adenomatous Polyposis Coli Protein; Animals; Carcinogenesis; Chemokine CCL2; Colorectal Neoplasms; Curcumin; Disease Models, Animal; Gene Expression Regulation, Neoplastic; HCT116 Cells; Humans; Inflammation; Interleukin-6; Intestinal Polyps; Intestines; Mice; NF-kappa B

Acute lung injury/acute respiratory distress syndrome (ALI/ARDS) is one type of respiratory failure characterized by rapid onset of widespread inflammation in the lungs. Curcumin has been reported to be an anti-inflammatory factor through enhancing the function of regulatory T cells (Tregs). This study aimed to explore the effect of curcumin on the differentiation of Tregs and the role of curcumin in ALI/ARDS.. A cecal ligation and puncture (CLP)-induced acute lung injury mouse model was used to explore the effect of curcumin in ALI/ARDS. The severity of lung injury was evaluated. Immunohistochemistry of IL-17A and MPO in lung tissue was examined. Treg-related cytokine levels in serum and bronchoalveolar lavage fluid (BALF) were tested. The expression of nuclear factor-kappa B (NF-κB) in lung tissue was detected. Macrophages in lung tissue were detected by immunofluorescence. Splenic CD4+CD25+FOXP3+ Tregs were quantified, and the differentiation of Tregs from naïve CD4 + T cell and STAT5 was evaluated. The expression of IL-10 during naïve CD4 + T cell differentiation in vitro was tested.. Curcumin alleviated lung injury in the induced CLP mouse model and suppressed inflammation. IL-17A, MPO-producing neutrophils, and NF-κB p65 expression in lungs of CLP mice decreased significantly after pretreatment with curcumin. We found curcumin could regulate M1/M2 macrophage levels in lungs of CLP mice. This may have been through regulating the differentiation of Tregs and the production of Treg-derived IL-10. Treg-derived IL-10 is the main factor that could affect macrophage polarization. We found curcumin could increase Treg proportions in vivo and up-regulate IL-10 expression in serum and BALF of CLP mice. In our in vitro experiments, we found curcumin could promote Treg differentiation and increase the production of IL-10.. Curcumin can reduce the degree of severity of ALI and uncontrolled inflammation through promoting the differentiation of naïve CD4 + T cells to CD4+ CD25+ FOXP3+ Tregs. Curcumin promotes the conversion of macrophages from M1 to M2. The differentiation of Tregs induced by curcumin may be one source of IL-10 immune modulation.

Topics: Acute Lung Injury; Animals; Anti-Inflammatory Agents; Bronchoalveolar Lavage Fluid; CD4-Positive T-Lymphocytes; Cell Differentiation; Curcumin; Cytokines; Disease Models, Animal; Female; Inflammation; Interleukin-10; Macrophages; Male; Mice; Mice, Inbred C57BL; Respiratory Distress Syndrome; T-Lymphocytes, Regulatory

Oxaliplatin (OXA)-induced liver injury is one of the main limiting factors affecting the efficacy of OXA-based chemotherapy in patients with colorectal liver metastases. In addition, oxidative stress is an important pathophysiological mechanism of OXA-induced liver injury. Therefore, dietary antioxidants may decrease or prevent hepatic toxicity in vivo and be beneficial to OXA-based chemotherapy.. An experimental OXA-induced liver injury animal model was established, and the protective effects of curcumin (CUR) against OXA-induced liver injury were investigated. ELISA was used to determine the levels of MDA, SOD, CAT, and GSH in liver tissue. The effect of CUR treatment on the expression of cytokines and the Nrf2 pathway was determined by real-time PCR and Western blotting.. CUR treatment alleviated OXA-induced hepatic pathological damage and splenomegaly. The protective effect of CUR was demonstrated to be correlated with inhibition of oxidative stress, inflammation, and the coagulation system. Furthermore, Western blotting revealed that CUR treatment reverses the suppression of Nrf2 nuclear translocation and increases the expression of HO-1 and NOQ1 in mice with OXA-induced liver injury. Moreover, the Nrf2 activation and hepatoprotective effect of CUR were abolished by brusatol.. Curcumin attenuates oxaliplatin-induced liver injury and oxidative stress by activating the Nrf2 pathway, which suggests that CUR may be potentially used in the prevention and treatment of OXA-induced liver injury.

Topics: Animals; Antineoplastic Agents; Chemical and Drug Induced Liver Injury; Curcumin; Disease Models, Animal; Dose-Response Relationship, Drug; Inflammation; Injections, Intraperitoneal; Mice; Mice, Inbred BALB C; NF-E2-Related Factor 2; Oxaliplatin; Oxidative Stress; Protective Agents; Structure-Activity Relationship

Diabetic wound characterizes with a delayed repair as a result of the lack of neoangiogenesis and the excess of inflammation. Natural products such as curcumin have shown great promises in their regulatory potentials on inflammation and angiogenesis. However, natural agents have several shortages in their bioavailability and stability when used in vivo. In this study, we have evaluated the efficacy of a topical formulation of curcumin in the enhancement of diabetic wound repair. Streptozocin-induced diabetic mice were wounded, and cream of curcumin (1%) was applied topically to wounds twice daily for different treatment periods. Inflammation, neoangiogenesis, and re-epithelialization were evaluated in each experimental group. Wounds of animals treated with curcumin showed an enhanced neoangiogenesis. Application of topical curcumin also increased the expression level of RelA as the main subunit of the nuclear factor-κB (NF-κB) signalling pathway. However, no significant effects on macrophage polarization and re-epithelialization were observed in the curcumin-treated animals. Our study using a higher concentration of curcumin in the form of a topical cream further confirmed the efficacy of curcumin as an angiogenesis-promoting agent; however, it also conveyed uncertainty over the claimed regulatory effects of curcumin on inflammation. SIGNIFICANCE OF THE STUDY: Diabetes results in several complications such as impaired cutaneous wound repair. Excess of inflammation and lack of angiogenesis are among the main causes of delayed healing in diabetes. Curcumin is famous for its anti-inflammatory properties. However, when in the body curcumin has shown to have a limited benefit unless in high-dosage consumes. This is because of its poor absorption from digestive system and its bioavailability. In this study, we have used a topical formulation of curcumin at a relatively high concentration to enhance the healing of a diabetic wound in an animal model of diabetes. We also have studied different cellular and molecular mechanisms by which curcumin may help the wound repair. Our results re-emphasize the proangiogenic potential of curcumin in diabetic wound environment.

Topics: Administration, Topical; Animals; Anti-Inflammatory Agents; Curcuma; Curcumin; Diabetes Mellitus, Experimental; Disease Models, Animal; Dose-Response Relationship, Drug; Inflammation; Male; Mice; Mice, Inbred C57BL; Neovascularization, Pathologic; Skin; Streptozocin; Wound Healing

Benzo(a)pyrene (BaP) is a well-known carcinogen and enhances oxidative stress and apoptosis and also alters several molecular pathways. Curcumin is an active ingredient of

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Apoptosis; Benzo(a)pyrene; C-Reactive Protein; Curcuma; Curcumin; Inflammation; Inflammation Mediators; Interleukin-6; Lung; Lung Injury; Male; Oxidative Stress; Plant Extracts; Rats; Rats, Sprague-Dawley; Spices; Tumor Necrosis Factor-alpha

BACKGROUND Cerebral ischemia/reperfusion (I/R) injury contributes to mortality and morbidity in preterm infants. Curcumin has been shown to exert neuro-protective effects in the central nervous system (CNS). The aim of this study was to investigate the neuro-protective activity of curcumin and the possible underlying molecular mechanisms. MATERIAL AND METHODS A hypoxia/reoxygenation (H/R) protocol was used to simulate I/R injury in vitro. Isolated neonatal neurons were pre-treated with curcumin at serially diluted concentrations and exposed to H/R injury. Cell viability and apoptosis were assessed by MTT and flow cytometry, respectively. Contents of TNFa and IL6 in supernatant of cell culture medium were detected by ELISA. Protein expression, phosphorylation, and nuclear translocation levels were studied by Western blotting. RESULTS H/R reduced cell viability and increased apoptosis of neurons. H/R significantly increased Wnt5a expression, JNK1 phosphorylation, and NF-kappaB nuclear translocation. Moreover, expression levels of cleaved caspase3, TNFalpha, and IL6 were elevated in H/R-exposed neurons. Curcumin pre-treatment significantly increased cell viability and inhibited apoptosis of neurons exposed to H/R, in a concentration-dependent manner. Moreover, curcumin pre-treatment significantly decreased expression levels of Wnt5a, IL6, TNFalpha, and phosphorylation level of JNK1, as well as the nuclear translocation level of NF-kappaB in H/R-exposed neurons, in a concentration-dependent manner. CONCLUSIONS Curcumin exerted neuro-protective effects against H/R-induced neuron apoptosis and inflammation by inhibiting activation of the Wnt/JNK1 signaling pathway.

Topics: Animals; Apoptosis; Cell Line; Cell Survival; Curcumin; Female; Fetus; Hypoxia; Inflammation; Neurons; Neuroprotective Agents; Pregnancy; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species; Reperfusion Injury; Signal Transduction; Wnt Signaling Pathway

Curcumin exhibits anti-inflammatory properties and has been used for centuries in traditional medicine and as dietary supplement. Data from clinical trials has strengthened the notion that curcumin may exert an anti-inflammatory and immunosuppressive role in patients with psoriatic disease, but its mode of action has remained elusive. We hypothesized that curcumin could inhibit interferon (IFN)-γ and interleukin (IL)-17 production in peripheral blood mononuclear cells from patients with psoriasis and psoriatic arthritis (PsA). To this end, we assessed the in vitro effect of curcumin on IFN-γ production by cluster differentiation (CD)4(+), CD8(+) T cells, natural killer (NK) and NKT cells and on IL-17 production by CD4(+) T cells from 34 patients with psoriatic disease (22 with psoriasis and 12 with PsA); 15 normal subjects were included as healthy controls. We also assessed the effect of curcumin on signal transducer and activator of transcription (STAT)3 activation. Curcumin significantly decreased, in a dose dependent manner, IFNγ-production by CD4(+) and CD8(+) T cells, and NK and NKT cells in patients with psoriatic disease and healthy controls. It also decreased IL-17 production by CD4(+) T cells (Th17). At the molecular level, curcumin increased STAT3 serine 727 phosphorylation intensity and p-STAT3(+) CD4(+) T cells in patients with PsA and psoriasis. In conclusion, curcumin in vitro inhibits pro-inflammatory IFN-γ and IL-17 production in psoriatic disease, and this may strengthen its role as a dietary immunosuppressant in patients with this disease.

Topics: Adult; Aged; Anti-Inflammatory Agents; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Curcumin; Diet; Female; Humans; Immunosuppressive Agents; Inflammation; Interferon-gamma; Interleukin-17; Killer Cells, Natural; Male; Middle Aged; Psoriasis; STAT3 Transcription Factor

Temporomandibular joint osteoarthritis (TMJ OA) is a complex multifactorial disease that can be induced by inflammation and oxidative stress. Curcumin has been reported to have anti-inflammatory and antioxidant properties. Herein, the anti-inflammatory and antioxidant mechanisms of curcumin in TMJ OA were investigated. Curcumin treatment inhibited the expression of the inflammation mediators IL-6, iNOS, and COX-2 and of the matrix-degrading proteinases MMP-1, MMP-3, MMP-9, MMP-13, ADAMTS-4, and ADAMTS-5 and upregulated the mRNA levels of the cartilage anabolic factors COL2A1 and ACAN after IL-1β treatment. Curcumin treatment also decreased oxidative stress injury following IL-1β stimulation. Pathway analysis demonstrated that the ROS/Nrf2/HO-1-SOD2-NQO-1-GCLC signaling axis is a key axis through which curcumin activates the Nrf2/ARE pathway in TMJ inflammatory chondrocytes. Curcumin-induced anti-inflammatory and cartilage protective effects were significantly abrogated by specific Nrf2 siRNA. In vivo results demonstrated that curcumin treatment protected TMJ articular cartilage from progressive degradation. Our experimental results indicate that curcumin inhibits inflammation, oxidative stress, and the matrix degradation of TMJ inflammatory chondrocytes through the Nrf2/ARE signaling pathway, thereby exerting cartilage protective effects. This study provides insight into potential therapeutic approaches for TMJ OA.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Antioxidants; Arthritis, Experimental; Cartilage; Cell Survival; Cells, Cultured; Chondrocytes; Curcumin; Extracellular Matrix; Gene Silencing; Humans; Inflammation; Inflammation Mediators; Interleukin-1beta; Male; Mice; NF-E2-Related Factor 2; Oxidative Stress; Rats, Sprague-Dawley; Response Elements; Signal Transduction; Temporomandibular Joint

The present study aimed to assess the effect of curcumin (Cur) on carotid artery restenosis following carotid endarterectomy (CEA) and its associated mechanism in vivo and in vitro.. Ang II was used to induce excessive proliferation of rabbit aortic smooth muscle cells (CCC-SMC-1) in order to establish a hemadostenosis cell model. Similarly, the animal model of carotid artery restenosis was established by carotid artery gas drying injury combined with high-fat feed prior to CEA. CCC-SMC-1 cells and animals were treated by Cur and its effects on neointimal hyperplasia, inflammation and oxidative stress were detected and observed. The proteins that were associated with the Raf/MEK/ERK pathway were detected in cells and rabbit carotid artery tissues.. Cur inhibited the proliferation of smooth muscle cells and neointimal formation and reduced the inflammation and oxidative stress indices. Concomitantly, Cur reduced the phosphorylation of the Raf/MEK/ERK pathway proteins.. Cur could inhibit carotid restenosis following CEA by inhibiting the activation of the Raf/MEK/ERK pathway.

Topics: Animals; Apoptosis; Carotid Artery Injuries; Cell Cycle; Cell Survival; Cells, Cultured; Curcumin; Dose-Response Relationship, Drug; Endarterectomy, Carotid; Inflammation; Male; Oxidative Stress; Rabbits; Structure-Activity Relationship

An environmentally friendly octenylsuccinic anhydride modified pH-sensitive chitosan-octenylsuccinic anhydride (OSA-CS) was synthesized. The critical micelle concentration (CMC) of the modified chitosan was 27 μg/mL, the graft polymers can form solubilized curcumin (CUR) and quercetin (QUE) nanoparticles. The drug-loaded nanoparticles had high encapsulation efficiency and drug loading content, the self-assembly of graft polymers formed spherical uniform nanoparticles with an approximate diameter of 150-180 nm. The nanoparticles were stable under storage conditions and in serum. The results revealed that OSA-CS exhibited excellent biocompatibility, no cytotoxicity. Additionally, the results of pH sensitivity and drug release experiments showed that the nanoparticles were highly sensitive to weakly acidic conditions (pH 6.0) and showed a faster release rate, while they were reasonably stable at physiological conditions (pH 7.4). The drug-loaded nanoparticles exhibited higher cellular uptake in vitro, and exhibited stronger anti-inflammatory and antioxidant efficacy. Therefore, OSA-CS-based nanoparticles are a promising hydrophobic drug delivery system for pH-response targeting therapy.

Topics: Anhydrides; Animals; Anti-Inflammatory Agents, Non-Steroidal; Antioxidants; Cell Proliferation; Chitosan; Curcumin; Drug Carriers; Drug Liberation; Hydrogen-Ion Concentration; Inflammation; Lipopolysaccharides; Macrophages; Male; Mice; Nanoparticles; Oxidative Stress; Quercetin; Reactive Oxygen Species

Toll-like receptor 4 (TLR4) pathway is one of the major pathways that mediate the inflammation in human body. There are different anti-inflammatory drugs available in the market which specifically act on different signaling proteins of TLR4 pathway but they do have few side effects and other limitations for intended use in human body. In this study, Curcumin and its different analogs have been analyzed as the inhibitors of signaling proteins, i.e. Cycloxygenase-2 (COX-2), inhibitor of kappaβ kinase (IKK) and TANK binding kinase-1 (TBK-1) of TLR4 pathway using different computational tools. Initially, three compounds were selected for respective target based on free binding energy among which different compounds were reported to have better binding affinity than commercially available drug (control). Upon continuous computational exploration with induced fit docking (IFD), 6-Gingerol, Yakuchinone A and Yakuchinone B were identified as the best inhibitors of COX-2, IKK, and TBK-1 respectively. Then their drug-like potentialities were analyzed in different experiments where they were also predicted to perform well. Hopefully, this study will uphold the efforts of researchers to identify anti-inflammatory drugs from natural sources.

Topics: Catechols; Computational Chemistry; Curcumin; Cyclooxygenase 2; Diarylheptanoids; Fatty Alcohols; Guaiacol; Humans; I-kappa B Kinase; Inflammation; Lipopolysaccharides; NF-kappa B; Pharmaceutical Preparations; Protein Serine-Threonine Kinases; Signal Transduction; Toll-Like Receptor 4

Ulcerative colitis (UC) is a chronic inflammatory bowel disease that affects the mucosa and submucosa of colon. The pathogenesis of ulcerative colitis (UC) is related to reduced antioxidant capacity and increased inflammatory processes. Reactive oxygen metabolites are the potent inflammatory mediators that may be involved in tissue injury in inflammatory bowel disease. Conventional drug therapies for UC come with a myriad of side effects which further raise the need for natural bioactive agents. Curcumin has proven to be beneficial in the prevention and treatment of a number of inflammatory diseases, but due its poor bioavailability, the therapeutic applications are limited. Thus, to enhance its bioavailability, a new formulation - curcumin-galactomannoside (CGM)- was made by complexing curcumin with galactomannans derived from fenugreek. The present study aims to evaluate the effects of CGM on experimental UC model. Adult male Wistar rats were divided into 5 groups: normal control rats (NC); ulcerative colitis control rats (UC); UC + sulfasalazine (SS) treated; UC + curcumin (CM) treated; and UC + CGM supplemented for 21 days. The colonic mucosal injury was assessed by macroscopic and histological examination, along with evaluation of antioxidant status, inflammatory mediators, and gene expressions. Administration of CGM significantly enhanced antioxidant activities and decreased the level of inflammatory mediators and also suppressed the expression of inflammatory markers as compared with other groups. In conclusion, findings from these results reveal that CGM exerts marked curative effects on acute experimental colitis, possibly by regulating the antioxidant status and modulating inflammatory cascade.

Topics: Acetic Acid; Animals; Anti-Ulcer Agents; Colitis, Ulcerative; Curcumin; Drug Combinations; Galactose; Inflammation; Intestinal Mucosa; Male; Mannosides; Oxidative Stress; Plant Extracts; Rats; Rats, Wistar; Trigonella

In a previous article, we reported on the physico-chemical properties of cellulose-based scaffolds derived from sugar-cane bagasse and their preliminary in vitro assessment. In view of skin tissue regeneration, we here present our findings of an extensive in vitro testing of these scaffolds using key cells involved in the wound healing cascade namely fibroblasts, keratinocytes, endothelial cells and macrophages either singly or in various combinations to mimic in vivo conditions. Inflammation was quantified using TNF-α. In vivo biocompatibility as well as wound healing potential of the scaffolds was demonstrated using Wistar rats. Finally, we discuss the effect of curcumin-loaded scaffolds on inflammation and angiogenesis in vitro and in vivo. Nanosilica extracted from sugar-cane bagasse ash was also loaded in the scaffolds and its effect on biological response was assessed.

Topics: Animals; Biocompatible Materials; Cell Communication; Cell Survival; Cellulose; Curcumin; Endothelial Cells; Female; Fibroblasts; HaCaT Cells; Humans; Inflammation; Keratinocytes; Macrophages; Male; Mice; Neovascularization, Physiologic; Rats; Rats, Wistar; RAW 264.7 Cells; Regeneration; Saccharum; Skin; Skin Physiological Phenomena; Tissue Engineering; Tissue Scaffolds; Wound Healing

Novel coronaviruses (CoV) have emerged periodically around the world in recent years. The recurrent spreading of CoVs imposes an ongoing threat to global health and the economy. Since no specific therapy for these CoVs is available, any beneficial approach (including nutritional and dietary approach) is worth investigation. Based on recent advances in nutrients and phytonutrients research, a novel combination of vitamin C, curcumin and glycyrrhizic acid (VCG Plus) was developed that has potential against CoV infection. System biology tools were applied to explore the potential of VCG Plus in modulating targets and pathways relevant to immune and inflammation responses. Gene target acquisition, gene ontology and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment were conducted consecutively along with network analysis. The results show that VCG Plus can act on 88 hub targets which are closely connected and associated with immune and inflammatory responses. Specifically, VCG Plus has the potential to regulate innate immune response by acting on NOD-like and Toll-like signaling pathways to promote interferons production, activate and balance T-cells, and regulate the inflammatory response by inhibiting PI3K/AKT, NF-κB and MAPK signaling pathways. All these biological processes and pathways have been well documented in CoV infections studies. Therefore, our findings suggest that VCG Plus may be helpful in regulating immune response to combat CoV infections and inhibit excessive inflammatory responses to prevent the onset of cytokine storm. However, further in vitro and in vivo experiments are warranted to validate the current findings with system biology tools. Our current approach provides a new strategy in predicting formulation rationale when developing new dietary supplements.

Topics: Anti-Inflammatory Agents; Ascorbic Acid; Coronavirus; Coronavirus Infections; Curcuma; Curcumin; Cytokines; Drug Combinations; Drug Delivery Systems; Gene Ontology; Glycyrrhiza; Glycyrrhizic Acid; Humans; Immunity, Innate; Inflammation; Interferons; Plant Extracts; Signal Transduction; Systems Biology; T-Lymphocytes; Vitamins

Curcumin presents some therapeutic effects including anti-cancer and anti-inflammation. Herein, we centred on the functional role of curcumin in cerebral ischaemia injury and its potential molecular mechanisms.. Microarray analysis was used for excavating crucial genes in cerebral ischaemia. PC12 cells were subjected to oxygen-glucose deprivation and reoxygenation (OGD/R) to imitate cerebral ischaemia/reperfusion (I/R) injury in vitro. Cell viability and apoptosis abilities were evaluated by Cell Counting Kit-8 and flow cytometry assays. qRT-PCR, Western blot and enzyme-linked immunosorbent assays were performed to assess the concentrations of related genes.. By enquiring GEO dataset, C-C motif chemokine ligand 3 (CCL3) was profoundly upregulated in cerebral I/R injury model. And CCL3 was found to be highly expressed in PC12 cells suffered from OGD/R. Moreover, we found that CCL3 was a potential target of curcumin in cerebral I/R injury. More importantly, the following experiments illustrated that curcumin inhibited the expression of CCL3 in OGD/R model and reduced cell apoptosis and inflammation. Moreover, high expression levels of TLR4, MyD88, p-NF-κB P65, p-P38 MAPK and p-IκBα in OGD/R model were inhibited by curcumin.. Our study manifested that curcumin might be a meritorious drug for the treatment of cerebral ischaemia by acting on CCL3.

Topics: Animals; Apoptosis; Brain Ischemia; Chemokine CCL3; Curcumin; Gene Expression Regulation; Glucose; Inflammation; Myeloid Differentiation Factor 88; Oxygen; p38 Mitogen-Activated Protein Kinases; PC12 Cells; Rats; Reperfusion Injury; Toll-Like Receptor 4; Transcription Factor RelA

Curcumin was demonstrated to be an active ingredient with anti-inflammatory effects. This research was to investigate the effects of curcumin. We found that curcumin promoted cell viability and suppressed cell apoptosis. Meanwhile, curcumin decreased the level of cleaved caspase-3 and the release of TNF-α, IL-1β, IL-6, but increased IL-10 release in LPS-treated BV2 cells. miR-362-3p expression was upregulated by curcumin, while TLR4 expression was downregulated. Besides, we observed that the cytoprotective effects of curcumin were lost when miR-362-3p was silenced. TLR4 was a direct target gene of miR-362-3p. Moreover, miR-362-3p deletion attenuated the cytoprotective effects of curcumin by regulating TLR4 expression in LPS-induced BV2 cells. Furthermore, curcumin suppressed p-p65 expression via regulating miR-362-3p/TLR4 axis. We discovered that curcumin exhibited protective effects against LPS-triggered cell injury via modulating miR-362-3p/TLR4 axis through NF-κB pathway.

Topics: Animals; Cell Line; Cell Survival; Curcumin; Cytokines; Inflammation; Lipopolysaccharides; Microglia; MicroRNAs; NF-kappa B; Rats; Signal Transduction; Toll-Like Receptor 4; Tumor Necrosis Factor-alpha

Interleukin (IL)-35, which has an anti-inflammatory role in acute respiratory distress syndrome (ARDS)/acute lung injury (ALI), is relatively promising as a drug target. Studies have shown that curcumin may play a therapeutic role in ALI and enhance the suppressive function of regulatory T cells (Tregs). To illustrate the effect of curcumin on the regulation of Treg cell differentiation and expression of IL-35, we built a cecal ligation and puncture (CLP)-induced acute lung injury mouse mode with curcumin pretreatment. The expression of IL-35 in serum, severity of lung injury, IL-17A in lung tissue, survival rate, Treg-related cytokines levels in serum, nuclear factor-kappa B (NF-κB)'s nuclear translocation in lung tissue, and splenic CD4+CD25+FOXP3+ Tregs were assessed. Furthermore, the proportion of Tregs, STAT5, and IL-35 expression during naïve CD4+ T cell differentiation in vitro was measured. Compared with the CLP group, the increased IL-35 expression in CLP with the curcumin pretreatment (CLP + Cur) group was consistent with the decreased severity of lung injury, IL-17A protein levels in lung tissue, and Treg-related cytokines levels. Pretreatment with curcumin, the survival rate climbed to 50%, while the mortality rate was 100% in the CLP group. In addition, splenic CD4+CD25+FOXP3+ Treg cells increased in the CLP + Cur group. In vitro, CD4+CD25+FOXP3+ Treg cells from naïve CD4+ T cells, STAT5 proportion, and IL-35 expression increased after curcumin treatment. These findings showed that curcumin might regulate IL-35 by activating the differentiation of Treg cells to control the inflammation in acute lung injury.

Topics: Acute Lung Injury; Animals; Anti-Inflammatory Agents, Non-Steroidal; Cecum; Cell Differentiation; Curcumin; Gene Expression; Inflammation; Interleukins; Male; Mice; Mice, Inbred C57BL; T-Lymphocytes, Regulatory

The polyphenolic spice and food coloring ingredient curcumin has beneficial effects in a broad variety of inflammatory diseases. Amongst them, curcumin has been shown to attenuate microglia reaction and prevent from glial scar formation in spinal cord and brain injuries.. We developed a protocol for the efficient encapsulation of curcumin as a model for anti-inflammatory drugs yielding long-term stable, non-toxic liposomes with favorable physicochemical properties. Subsequently, we evaluate the effects of liposomal curcumin in experimental models for neuroinflammation and reactive astrogliosis.. We could show that liposomal curcumin can efficiently reduce the reactivity of human microglia and astrocytes and preserve tissue integrity of murine organotypic cortex slices.. In perspective, we want to administer this curcumin formulation in brain implant coatings to prevent neuroinflammation and glial scar formation as foreign body responses of the brain towards implanted materials.

Topics: Animals; Anti-Inflammatory Agents; Astrocytes; Brain; Cell Line; Cell Survival; Curcumin; Gliosis; Humans; Inflammation; Lipopolysaccharides; Liposomes; Mice; Microglia; Neuroglia

Acute lung injury (ALI) is a pathologic condition responsible for incurable human chronic respiratory diseases. Recent studies have shown the involvement of the glycoprotein, IL17A secreted by IL-17 producing cells in chronic inflammation. The current investigation was carried out to study the IL-17A mediated activation of SMAD and non- SMAD signaling in alveolar epithelial cells and to assess the putative modulatory role of curcumin. C57BL/6 mice were exposed to IL-17A and curcumin was administered as an intervention to modulate the IL-17A-induced alveolar damage. Techniques like Immunofluorescence and real-time PCR were used. We found elevated expression of IL-17A and IL-17A-associated signaling pathways to be activated in mice lung tissues. Curcumin intervention in vivo promoted the resolution of IL-17A-induced ALI and attenuated pulmonary damage. Increase phosphorylation of non- SMAD proteins like P-EGFR, P-STAT-1, STAT-3, P-JAK-1/2, P-JNK, and also SMAD proteins like P- SMAD 2/3 and TGF-β1 was encountered upon IL-17A exposure, while curcumin intervention reversed the protein expression levels. Curcumin was found to block mRNA expressions of non- SMAD genes EGFR, JNK-1, JAK1, JAK2, STAT-1, STAT-3, MAPK14, also of TGF-β1 and SMAD genes like SMAD 2, SMAD 3. However, mRNA expressions of SMAD 6 and SMAD 7 were increased upon curcumin intervention. Our study indicates that IL-17A participates in the development of ALI in both SMAD dependent and independent manner and the IL-17A signaling components were effectively controlled by curcumin, suggesting probable anti-inflammatory use of curcumin during ALI.

Topics: Acute Lung Injury; Alveolar Epithelial Cells; Animals; Curcumin; Inflammation; Interleukin-17; Lung; Male; Mice; Mice, Inbred C57BL; Signal Transduction; Smad Proteins; Transforming Growth Factor beta1

Neuroinflammation has a key role in seizure generation and perpetuation in the neonatal period, and toll-like receptor 4 (TLR4) pathway has a prominent role in neuroinflammatory diseases. Administration of antioxidants and targeting TLR4 in the embryonic period may protect rat offspring against the next incidence of febrile seizure and its harmful effects. Curcumin and hesperidin are natural compounds with anti-inflammatory and antioxidant properties and have an inhibitory action on TLR4 receptors. We evaluated the effect of maternal administration of curcumin and hesperidin on infantile febrile seizure and subsequent memory dysfunction in adulthood. Hyperthermia febrile seizure was induced on postnatal days 9-11 on male rat pups with 24 h intervals, in a Plexiglas box that was heated to ~45 °C by a heat lamp. We used enzyme-linked immunosorbent assay, Western blotting, malondialdehyde (MDA), and glutathione (GSH) assessment for evaluation of inflammatory cytokine levels, TLR4 protein expression, and oxidative responses in the hippocampal tissues. For assessing working memory and long-term potentiation, the double Y-maze test and Schaffer collateral-CA1 in vivo electrophysiological recording were performed, respectively Our results showed that curcumin and hesperidin decreased TNF-α, IL-10, and TLR4 protein expression and reversed memory dysfunction. However, they did not provoke a significant effect on GSH content or amplitude and slope of recorded fEPSPs in the hippocampus. In addition, curcumin, but not hesperidin, decreased interleukin-1β (IL-1β) and MDA levels. These findings imply that curcumin and hesperidin induced significant protective effects on febrile seizures, possibly via their anti-inflammatory and antioxidant properties and downregulation of TLR4.

Topics: Animals; Animals, Newborn; Anti-Inflammatory Agents; Antioxidants; Curcumin; Cytokines; Electrophysiological Phenomena; Female; Glutathione; Hesperidin; Hippocampus; Hyperthermia; Inflammation; Male; Malondialdehyde; Maze Learning; Memory, Short-Term; Mothers; Oxidative Stress; Rats, Wistar; Seizures, Febrile; Toll-Like Receptor 4

Ischemia/reperfusion (I/R) is one of the most important causes of acute kidney injury (AKI), a clinical syndrome with kidney dysfunction and high mortality rates. New diagnostic biomarkers need to be defined to better illuminate the pathophysiology of AKI. For the first time, we aim to investigate the protective effects of Curcumin which is known for its antioxidant and anti-inflammatory properties and 12/15 lipoxygenase inhibitor LOXblock-1 on I/R induced AKI by modulating inflammatory processes, oxidative stress, apoptosis and semaphorin-plexin pathway.. The rats were divided into five groups, with eight animals per group: Sham, I/R, I/R + DMSO (1%, i.p.), I/R + Curcumin (100 mg/kg, i.p.), I/R + LOXblock-1 (2 μg/kg, i.p.).. The renal function biomarkers (BUN, CREA and UA) in serum were significantly increased in the I/R group. The inflammatory (TNF-α, IL-6 and MCP-1), apoptotic (CYCS and CASP3) and oxidative stress parameters (MDA, MPO, TAS and TOS) measured by ELISA were significantly increased in the I/R group. In histopathological analysis, it was observed that I/R caused serious damage to kidney tissue. SEMA3A was found to increase both serum level and mRNA expression in I/R group. It was observed that curcumin and LOXblock-1 reduce inflammatory processes, oxidative stress and apoptosis via the semaphorin-plexin pathway by both measurements and histopathological analysis. Curcumin was proved more effective than LOXblock-1 with its antioxidant feature in I/R injury.. The current study reveals the protective effects of Curcumin and LOXblock-1 on acute kidney injury by suppressing SEMA3A as a new biomarker.

Topics: Acute Kidney Injury; Animals; Anti-Inflammatory Agents, Non-Steroidal; Apoptosis; Benzene Derivatives; Cell Adhesion Molecules; Curcumin; Inflammation; Lipoxygenase Inhibitors; Nerve Tissue Proteins; Oxidative Stress; Rats; Rats, Wistar; Reperfusion Injury; Semaphorin-3A; Semaphorins

Curcumin alleviates septic acute kidney injury (SAKI); however, the underlying mechanism remained unclear. To explore this, SAKI cell model and mice model were conducted by using LPS and cecal ligation and puncture (CLP), respectively. Cell counting kit-8 (CCK-8) and enzyme-linked immunosorbent assay (ELISA) assays indicated that LPS reduced the viability, but upregulated the levels of tumor necrosis factor (TNF)-α and interleukin (IL)-6, whereas Curcumin pretreatment had no effect on viability, but reduced the levels of TNF-α and IL-6. Further assays showed that Curcumin partly attenuated the LPS-induced injury as the viability was enhanced, TNF-α and IL-6 expressions and cell apoptosis rates were reduced. Western blot analysis indicated that Janus kinase (JAK) 2/signal transducer and activator of transcription (STAT) 3, p-65-NF-κB and cell apoptosis pathways were activated by LPS but suppressed by Curcumin. Mice SAKI model further indicated that the serum Cystatin C (Cys-C), creatinine (Cr) and blood urea nitrogen (BUN) were increased within 24 h of model construction while those indicators were decreased at 48 h. Pretreated with Curcumin, NF-κB inhibitor (PDTC) or JAK2 inhibitor (AG-490) could weaken the renal histological injury and the increased serum Cys-C, Cr and BUN, IL-6 and TNF-α induced by CLP. Moreover, PDTC, AG-490 and Curcumin all significantly reversed the previously increased expressions of p-JAK2/STAT3, p-p65 and proapoptotic proteins in the mice with AKI. The present study revealed that Curcumin attenuated SAKI through inhibiting NF-κB and JAK2/STAT3 signaling pathways, and proposed that Curcumin could be a potential therapeutic agent for treating SAKI.

Topics: Acute Kidney Injury; Animals; Apoptosis; Cecum; Cell Line; Cell Survival; Curcumin; Humans; Inflammation; Janus Kinase 2; Ligation; Lipopolysaccharides; Male; Mice, Inbred C57BL; NF-kappa B; Punctures; Sepsis; Signal Transduction; STAT3 Transcription Factor

Bleomycin (BLM)-induced pulmonary fibrosis is characterized by inflammation in the alveoli, subsequent deposition of extracellular matrix (ECM) and myofibroblasts, and an impaired fibrinolytic system. Here, we describe major hematological changes, the IL-17A-mediated p53-fibrinolytic pathway, and the high throughput hits of liquid chromatography-mass spectrometry (LC-MS) analysis during the progression of pulmonary fibrosis and the therapeutic potential of curcumin against disease progression. C57BL/6 mice were exposed to BLM, followed by curcumin intervention after 24 and 48 h. Mice were sacrificed after 7 days to validate the hematological parameters, molecular pathways, and proteomics. Various techniques such as western blotting, immunofluorescence, reverse transcriptase polymerase chain reaction (RT-PCR), hematoxylin and eosin staining, Masson's trichrome staining, and immunohistochemistry were used to validate the proposed theory. LC-MS analysis was performed using a Q-Orbitrap mass spectrometer. The Schrödinger approach was used to perform the

Topics: Animals; Bleomycin; Curcumin; Inflammation; Lung; Mice; Mice, Inbred C57BL; Molecular Docking Simulation; Proteomics; Pulmonary Fibrosis

In this study, we developed oral core-shell nanoparticles composed of curcumin nanocrystals in the core and chitosan/alginate multilayers in the shell for inflammation-targeted alleviation of ulcerative colitis (UC). The release rate of curcumin from the core-shell nanoparticles was low at a pH mimicking the stomach and small intestine, whereas it was higher at a pH mimicking the colon. Further, biodistribution studies in the gastrointestinal tract of mice showed that distribution of nanoparticles was significantly higher in the colon than that in the stomach and small intestine. Quantitative analysis of drugs in colonic tissues and confocal imaging of colons revealed preferential accumulation of nanoparticles in inflamed tissues than that in healthy tissues.

Topics: Animals; Colitis, Ulcerative; Curcumin; Drug Carriers; Drug Delivery Systems; Hydrogen-Ion Concentration; Inflammation; Mice; Nanoparticles; Polyelectrolytes; Tissue Distribution

Drugs for the treatment of Alzheimer's disease (AD) are in urgent demand due to the unmet need and the social burden associated with the disease. Curcumin has been historically considered as a beneficial product for anti-aging and AD. However, many efforts to develop curcumin for clinical use are hindered mainly due to its poor bioavailability. Recent development in drug delivery and structural design has resolved these issues. In this study, we identified a small molecule, TML-6, as a potential drug candidate for AD through screening a panel of curcumin derivatives using six biomarker platforms related to aging biology and AD pathogenesis. The structural modification of TML-6 is designed to improve the stability and metabolism of curcumin. Cell biological studies demonstrated that TML-6 could inhibit the synthesis of the β-amyloid precursor protein and β-amyloid (Aβ), upregulate Apo E, suppress NF-κB and mTOR, and increase the activity of the anti-oxidative

Topics: Alzheimer Disease; Amyloid beta-Peptides; Amyloid beta-Protein Precursor; Animals; Behavior, Animal; Brain; Curcumin; Disease Models, Animal; Gene Expression Regulation; Humans; Inflammation; Mice; Microglia; Neuroprotective Agents; NF-E2-Related Factor 2; Plaque, Amyloid

Bisphenol A (BPA) has been shown to induce liver fibrosis in rodents. Therefore, this study examined the protective effect of a triple combination of curcumin (Cur), N-acetyl cysteine (NAC) and propolis (Prp) extract against BPA-induced hepatic fibrosis.. 100 Wistar male rats were equally assigned into 10 groups; one group was designated as control. 10 rats were gavaged with BPA (50 mg/kg/day) for 8 wk and left un-treated (BPA group). The remaining 80 rats were divided into 8 groups, distributed in 2 models. Protective model: rats were daily co-treated with BPA and Cur (100 mg/kg, p.o) or NAC (150 mg/kg, p.o) or Prp (200 mg/kg, p.o) or their combination for 8 wk. Preventive model: rats were daily treated with Cur or NAC or Prp or their combination for 4 wk before BPA administration and then in the same manner as protective model.. Current treatment interventions significantly alleviated BPA-induced hepatic damage and fibrosis. They also restored pro-oxidant/antioxidant balance, shifted cytokine balance towards the anti-inflammatory side, decreasing interleukin-1β/interleukin-10 ratio. Moreover, these compounds seem to exert anti-apoptotic effects by increasing the immunoexpression of B-cell lymphoma 2 in hepatocytes and decreasing hepatic caspase-3 content. Finally, they ameliorated extracellular matrix turn over through down-regulation of matrix metalloproteinase-9 and up-regulation of tissue inhibitor of matrix metalloproteinase-2 genetic expression.. Current treatments guarded against BPA-induced hepatic fibrosis due to their antioxidant, anti-inflammatory and anti-apoptotic properties, decreasing extracellular matrix turnover. Interestingly, the triple therapy provided hepatoprotection superior to monotherapy. Besides, prophylactic and concurrent treatments seem to be more effective than concurrent treatments.

Topics: Acetylcysteine; Animals; Apoptosis; Benzhydryl Compounds; Chemical and Drug Induced Liver Injury; Curcumin; Drug Therapy, Combination; Inflammation; Interleukins; Liver; Liver Cirrhosis; Male; Phenols; Propolis; Rats; Rats, Wistar

The anti-inflammatory effects of curcumin are well documented. However, the bioavailability of curcumin is a major barrier to its biological efficacy. Low-dose combination of complimentary bioactives appears to be an attractive strategy for limiting barriers to efficacy of bioactive compounds. In this study, the anti-inflammatory potential of curcumin in combination with chlorogenic acid (CGA), was investigated using human THP-1 macrophages stimulated with lipopolysaccharide (LPS). Curcumin alone suppressed TNF-α production in a dose-dependent manner with a decrease in cell viability at higher doses. Although treatment with CGA alone had no effect on TNF-α production, it however enhanced cell viability and co-administration with curcumin at a 1:1 ratio caused a synergistic reduction in TNF-α production with no impact on cell viability. Furthermore, an qRT-PCR analysis of NF-κB pathway components and inflammatory biomarkers indicated that CGA alone was not effective in reducing the mRNA expression of any of the tested inflammatory marker genes, except TLR-4. However, co-administration of CGA with curcumin, potentiated the anti-inflammatory effects of curcumin. Curcumin and CGA together reduced the mRNA expression of pro-inflammatory cytokines [TNF-α (~88%) and IL-6 (~99%)], and COX-2 (~92%), possibly by suppression of NF-κB (~78%), IκB-β-kinase (~60%) and TLR-4 receptor (~72%) at the mRNA level. Overall, co-administration with CGA improved the inflammation-lowering effects of curcumin in THP-1 cells.

Topics: Anti-Inflammatory Agents; Biological Availability; Cell Survival; Chlorogenic Acid; Curcumin; Cyclooxygenase 2; Drug Therapy, Combination; Humans; I-kappa B Kinase; Inflammation; Lipopolysaccharides; Macrophages; NF-kappa B; RNA, Messenger; Signal Transduction; THP-1 Cells; Toll-Like Receptor 4; Tumor Necrosis Factor-alpha

Neuroinflammation plays an important role in the pathophysiological process of various neurodegenerative diseases. It is well known that curcumin has obvious anti-inflammatory effects in various neuroinflammation models. However, its effect on the modulation of microglial polarization is largely unknown.. This study aimed to investigate whether curcumin changed microglia to an anti-inflammatory M2-phenotype by activating the AMP-activated protein kinase (AMPK) signaling pathway.. LPS treatment was used to establish BV2 cells and primary microglia neuroinflammation models. The neuroinflammation mouse model was established by an intracerebroventricular (ICV) injection of lipopolysaccharide (LPS) in the lateral septal complex region of the brain. TNF-α was measured by ELISA, and cell viability was measured by Cell Counting Kit-8 (CCK-8). The expression of proinflammatory and anti-inflammatory cytokines was examined by Q-PCR and Western blot analysis. Phenotypic polarization of BV2 microglia was detected by immunofluorescence.. Curcumin enhanced AMPK activation in BV2 microglial cells in the presence and absence of LPS. Upon LPS stimulation, the addition of curcumin promoted M2 polarization of BV2 cells, as evidenced by suppressed M1 and the elevated M2 signature protein and gene expression. The effects of curcumin were inhibited by an AMPK inhibitor or AMPK knockdown. Calmodulin-dependent protein kinase kinase β (CaMKKβ) and liver kinase B1 (LKB1) are upstream kinases that activate AMPK. Curcumin can activate AMPK in Hela cells, which do not express LKB1. However, both the CaMKKβ inhibitor and siRNA blocked curcumin activation of AMPK in LPS-stimulated BV2 cells. Moreover, the CaMKKβ inhibitor and siRNA weaken the effect of curcumin suppression on M1 and enhancement of M2 protein and gene expression in LPS-stimulated BV2 cells. Finally, curcumin enhanced AMPK activation in the brain area where microglia were over-activated upon LPS stimulation in an in vivo neuroinflammation model. Moreover, curcumin also suppressed M1 and promoted M2 signature protein and gene expression in this in vivo model.. Curcumin enhances microglia M2 polarization via the CaMKKβ-dependent AMPK signaling pathway. Additionally, curcumin treatment was found to be neuroprotective and thus might be considered as a novel therapeutic agent to treat the neurodegenerative disease such as Alzheimer's disease, Parkinson's disease, etc.

Topics: AMP-Activated Protein Kinases; Animals; Blotting, Western; Calcium-Calmodulin-Dependent Protein Kinase Kinase; Cell Differentiation; Curcumin; Disease Models, Animal; Inflammation; Mice; Microglia; Polymerase Chain Reaction; Signal Transduction

Although inflammation is a host defense mechanism, chronic inflammation mediates several diseases, including cancer, allergy, asthma, and autoimmune diseases, and reportedly, it is associated with a 60% mortality rate. There are several reports on the anti-inflammatory effects of Curcuma longa and Allium hookeri. However, although they can be used as culinary materials and have biological effects, they are not effective anti-inflammatory agents. In this study, we evaluated the synergic effect of C. longa and A. hookeri in order to confirm the possibility of a new anti-inflammatory agent. Based on cell viability and cytokine analyses, the appropriate ratio of C. longa and A. hookeri was confirmed using an air pouch animal model. Then, the anti-inflammatory effect of C. longa and A. hookeri co-treatment was evaluated by measuring the immune cell count and cytokines in the exudate and by comparing the morphological changes and cytokines in inflamed skin samples. Additionally, we evaluated the NF-κB/COX-2 pathway and iNOS levels. The active constituents detected in C. longa were demethoxycurcumin and bisdemethoxycurcumin, and that detected in A. hookeri was methylsulfonylmethane. An in vitro assessment determined the appropriate drug ratio as 3:7. In a carrageenan-induced inflammatory model, co-treatment effectively suppressed inflammatory cytokines, including IFN-γ, IL-1β, IL-6, IL-13, and IL-17, and recovered inflammation-related morphological changes in the skin. The anti-inflammatory effect of the co-treatment was mediated through the NF-κB/COX-2 pathway and iNOS inhibition. We concluded that co-treatment with C. longa and A. hookeri synergistically inhibited inflammation via the NF-κB/COX-2/iNOS pathway.

Topics: Allium; Animals; Anti-Inflammatory Agents; Cell Proliferation; Curcuma; Cyclooxygenase 2; Inflammation; Inflammation Mediators; Male; Mice; Mice, Inbred ICR; NF-kappa B; Plant Extracts; RAW 264.7 Cells; Skin

"Curcumae Radix", the dried rhizomes of Curcuma kwangsiensis documented in Chinese pharmacopoeia, has been traditionally used for the treatment of inflammatory and pain diseases, such as jaundice and red urine, cleaning the heart-fire and depression, arthralgia, and dysmenorrhea. However, according to literature surveys, anti-inflammatory and antinociceptive studies of C. kwangsiensis have been seldom reported so far.. The current study focuses on the anti-inflammatory and antinociceptive effects of C. kwangsiensis and discovering the bioactive compounds for its traditional usages both in vivo and in vitro, which could provide scientific justification about its traditional use.. The anti-inflammatory and antinociceptive assays of various layers (ME, EA, AQS) from C. kwangsiensis were achieved by carrageenan-induced paw edema and acetic acid-induced writhing animal models, respectively. The most bioactive part, EA layer was further phytochemically investigated by multiple step chromatography techniques. The structures of these isolates were unambiguously elucidated by means of extensive spectroscopic and chemical methods, and comparison with corresponding data of the reported literature. Four major sesquiterpenoids (4, 6, 14, and 15) were achieved for their anti-inflammatory and antinociceptive assays by the two aforementioned animal models in vivo. All the isolated compounds were evaluated for their anti-inflammatory effects via detecting inflammatory mediator releases (COX-2, IL-1β, and TNF-α) in RAW 264.7 macrophage cells induced by LPS.. The ME and EA layers significantly alleviated the paw edema caused by carrageenan and decreased the number of writhes induced by acetic acid at the dose of 200 and/or 100 mg/kg in comparison to the control group (p < 0.01/0.05), and the EA layer exhibited better activity than that of ME layer. Subsequent phytochemical investigation on EA layer of C. kwangsiensis exhibited that three new terpenoid compounds (1-3), identified as (12Z,14R)-7β-hydroxylabda-8(17),12-diene-14,15,16-triol (1), (12Z,14S)- 7β-hydroxlabda-8(17),12-diene-14,15,16-triol (2), and (4S)-hydroxy-(8)-methoxy-(5S)-(H)-guaia1(10),7(11)-dien-12,8-olide (3), together with twenty-two known analogs were isolated. Furthermore, four major sesquiterpenoids (4, 6, 14, and 15) significantly relieved the paw edema and number of writhes at 100 and/or 50 mg/kg (p < 0.05/0.01). Likewise, the majority of sesqui- and diterpenoids isolated could remarkably inhibited the secretion of inflammatory mediators (COX-2, IL-1β, and TNF-α) in LPS-stimulated RAW 264.7 macrophages cells at the concentration of 20 μg/mL, comparable to DXM used as the positive control. All the results suggested that EA layer from C. kwangsiensis possessed the anti-inflammatory and antinociceptive activities, and these sesqui- and diterpenoids could be the effective constituents responsible for relieving inflammation.. The present studies undoubtedly determined the anti-inflammatory and antinociceptive material basis of C. kwangsiensis, including the EA layer and its precise components, which presented equivalent or better anti-inflammatory effects than that of positive control (ASP/DXM) in vivo and in vitro. These results not only would account for scientific knowledge for traditional use of C. kwangsiensis, but also provide credible theoretical foundation for the further development of anti-inflammatory and antinociceptive agents.

Topics: Analgesics; Animals; Anti-Inflammatory Agents; Behavior, Animal; Curcuma; Disease Models, Animal; Inflammation; Inflammation Mediators; Macrophages; Male; Mice; Mice, Inbred ICR; Nociceptive Pain; Pain Perception; Pain Threshold; Plant Extracts; RAW 264.7 Cells; Terpenes

Osteoarthritis (OA) is a joint disease characterized by degeneration of cartilage, intra-articular inflammation, remodeling of subchondral bone and joint pain. The present study was designed to assess the therapeutic effects and the possible underlying mechanism of action of Manjarix, a herbal combination composed of ginger and turmeric powder extracts, on chemically induced osteoarthritis in rats. An OA model was generated by intra-articular injection of 50 μL (40 mg mL-1) of monosodium iodoacetate (MIA) into the right knee joint of rats. After one week of osteoarthritis induction, a comparison of the anti-inflammatory efficacy of indomethacin at an oral dose of 2 mg kg-1 daily for 4 successive weeks versus five decremental dose levels of Manjarix (1000, 500, 250, 125, and 62.5 mg kg-1) was performed. Serum inflammatory cytokines, interleukin 6, interleukin 8, and tumor necrosis factor alpha; C-telopeptide of type II collagen (CTX-II) and hyaluronic acid (HA) were measured, along with weekly assessment of the knee joint swelling. Pain-like behavior was assessed and knee radiographic and histological examination were performed to understand the extent of pain due to cartilage degradation. Manjarix significantly reduced the knee joint swelling, decreased the serum levels of IL6, TNF-α, CTX-II and HA, and reduced the pathological injury in joints, with no evidence of osteo-reactivity in the radiographic examination. Manjarix also significantly prevented MIA-induced pain behavior. These results demonstrate that Manjarix exhibits chondroprotective effects and can inhibit the OA pain induced by MIA, and thus it can be used as a potential therapeutic product for OA.

Topics: Animals; Anti-Inflammatory Agents; Arthralgia; Arthritis, Experimental; Cartilage, Articular; Collagen Type II; Curcuma; Cytokines; Disease Models, Animal; Edema; Female; Indomethacin; Inflammation; Iodoacetates; Joint Diseases; Knee Joint; Osteoarthritis; Pain; Plant Extracts; Rats; Rats, Wistar; Zingiber officinale

to evaluate the efficacy of oral administration of a novel composition composed of quercetin, curcumin, acetylcysteine in reducing pain in women affected by endometriosis, through the reduction of the inflammatory-hyperproliferative component of the ectopic endometrial tissue.. Thirty-three women with clinical diagnosis of endometriosis from at least 3 months have been enrolled. Patients have been treated daily with 200 mg of quercetin, 210 mg of dry extract of Curcuma longa (titrated at 95% in curcuminoids) and 150 mg of acetylcysteine (1 tablet of ALLIENDO. Overall, the results collected at the end of the treatment according to the parameters evaluated and above mentioned on the 33 patients enrolled, show a significative improvement in the reduction of pain symptoms associated to endometriosis (P<0.001 for dysmenorrhea, pelvic pain and dyspareunia). The use of NSAIDs together with an overall reduction of their dosage and time of assumption has been reduced as well. No significative side effects have been observed.. The aforementioned results suggest that administration of the composition described can represent a valuable adjuvant treatment in the reduction of pain symptomatology associated to endometriosis, triggered by inflammatory cascade and hyperproliferation of ectopic tissue.

Topics: Acetylcysteine; Curcuma; Dysmenorrhea; Dyspareunia; Endometriosis; Humans; Inflammation; Quercetin

Due to the complexity of the pathogenesis of Parkinson's disease (PD), multimodal treatment may achieve better results. In this study, a series of coumarin Mannich base derivatives were designed and synthesized as multifunctional agents for PD treatment. Among the derivatives, 3-(3-(dimethylamino)propanoyl)-7-hydroxy-5-methyl- 2H-chromen-2-one hydrochloride (24) exhibited the most potent and selective hMAO-B inhibitory activity, and anti-inflammatory and neuroprotective effects in the in vitro studies. It significantly attenuated PD-associated behavioural deficits in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model of PD. Furthermore, preliminary mechanistic studies indicated that 24 could selectively inhibit MAO-B activity, decrease the neuroinflammatory process, and protect tyrosine hydroxylase-immunopositive dopaminergic neurons. These results suggest that 24 is a promising multifunctional agent for effective therapy for PD.

Topics: Animals; Coumarins; Dose-Response Relationship, Drug; Drug Discovery; Humans; Inflammation; Male; Mannich Bases; Mice; Mice, Inbred C57BL; Molecular Docking Simulation; Molecular Structure; Monoamine Oxidase; Monoamine Oxidase Inhibitors; Neuroprotective Agents; Parkinson Disease; Structure-Activity Relationship; Tumor Cells, Cultured

Poly-l-lactic acid (PLLA) is widely used in clinic, for example, as biodegradable coronary artery stents. However, inflammatory responses in endothelial cells associated with PLLA degradation are relatively undefined. We previously reported inflammation in human aortic endothelial cells (HAEC) in vitro and in vivo. Here, we further assessed inflammatory injury, including cell migration, cell function, and inflammatory cytokines expressed in HAEC treated with PLLA and curcumin by CCK-8, wound healing assay, ELISA, and Western blot. Significant inhibition of cell migration, remarkable dysfunction, and inflammatory responses were found in HAEC treated with PLLA degradation extract, and these effects were alleviated by Cur treatment. These findings indicated that cautious evaluation of biodegradable polymers should be performed, and Cur represents a promising anti-inflammatory agent for alleviating endothelial dysfunction and inflammation caused by PLLA degradation. In addition, Cur should be further studied experimentally in in vivo experiments on animal models as a potential therapeutic to reduce thrombosis of biodegradable polymer stents.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Aorta; Biocompatible Materials; Cell Line; Cell Survival; Curcumin; Cytokines; Endothelial Cells; Humans; Inflammation; Polyesters

Rheumatoid arthritis (RA) is a chronic articular synovial inflammatory disease. The precise etiology underlying the pathogenesis of RA remains unknown. We aimed to investigate the inhibitory effect of curcumin analog FM0807 (curcumin salicylate monoester, 2-hydroxy-, 4-[(1E,6E)-7-(4-hydroxy-3-methoxyphenyl)-3,5-dioxo-1,6-heptadien-1-yl]-2-methoxyphenyl ester) on experimental RA and investigate its possible mechanisms of action.. Rats with Freund's complete adjuvant (FCA)-induced arthritis (AIA) were administered aspirin (0.1 mmol.kg. Compared with AIA group, FM0807 reduced the AI and swelling of the injected hind paw in a dose-dependent manner, and inhibited increases in inflammatory cell infiltration, pannus formation and cartilage destruction. FM0807 also potently attenuated the increase in the expression of inflammatory factors TNF-α, IL-6 and IL-1β in synovial fluid, while IL-10 levels were also elevated. FM0807 significantly suppressed phosphorylation of extracellular-signal-regulated kinase (ERK) 1/2 (ERK1/2), c-Jun-N-terminal kinase (JNK) 1/2 (JNK1/2), p38MAPK, inhibitor of NF-κB kinase (IKK), IκB and NF-κB p65 protein, (all. FM0807 exerts its therapeutic effects on RA by inhibiting cartilage degeneration. FM0807 treatment might be an effective therapeutic approach for RA.

Topics: Animals; Anti-Inflammatory Agents; Arthritis, Experimental; Aspirin; Curcumin; Disease Progression; Edema; Freund's Adjuvant; Gene Expression Regulation; Hindlimb; Inflammation; Interleukin-10; Interleukin-1beta; Interleukin-6; Male; MAP Kinase Signaling System; Mitogen-Activated Protein Kinase 1; Mitogen-Activated Protein Kinase 3; NF-kappa B; Rats; Rats, Sprague-Dawley; Tarsus, Animal; Tumor Necrosis Factor-alpha

Microglia mediate multiple facets of neuroinflammation, which plays a double-edged role in various brain diseases via distinct microglial phenotypes (deleterious M1 and neuroprotective M2). Therefore, the inhibition of overactivated inflammatory M1 microglia by switching to the protective M2 phenotype appears to be a potential therapeutic strategy in neuroinflammatory disorders. Curcumin has been shown to exhibit anti-inflammatory and neuroprotective activities. The present study investigated the potential effects of curcumin on microglial M1/M2 polarization and elucidated the possible molecular mechanisms of action in vitro. In this study, the BV2 microglial cell line was pretreated with different curcumin concentrations in the presence or absence of lipopolysaccharide (LPS) to assess the anti-inflammatory efficacy of curcumin based on the morphological and inflammatory changes. The cytotoxicity of curcumin for BV2 cells was evaluated using the CCK-8 assay. Further, the effect of curcumin concentrations on LPS-induced BV2 cells was studied. The morphological changes were observed using an optical microscope and immunofluorescent staining. Nitric oxide (NO) expression was determined using the Griess reagent. The expression of cytokines and inflammatory mediators was also measured by ELISA, qRT-PCR, flow cytometry, and immunofluorescence. Western blot analysis was used to determine the levels of triggering receptor expressed on myeloid cells 2 (TREM2), toll-like receptor 4 (TLR4), nuclear factor-kappa B (NF-κB) p65, p-NF-κB p65, IκB, and p-IκB expression. Results showed that curcumin concentrations less than 10 μM did not induce any detectable cytotoxicity but decreased BV2 cell viability up to 20 μM. Curcumin inhibited LPS-induced microglial activation. Curcumin treatment switched the M1 pro-inflammatory phenotype to the M2 anti-inflammatory phenotype by decreasing the expression of M1 markers (i.e., iNOS, IL-1β, IL-6, and CD16/32) and elevating the expression of M2 markers (i.e., arginase 1, IL-4, IL-10, and CD206). Interestingly, curcumin attenuated the activation of TLR4/NF-κB pathways and the downregulation of TREM2 expression in LPS-activated BV2 cells. Collectively, these results suggest that curcumin significantly alleviates LPS-induced inflammation by regulating microglial (M1/M2) polarization by reducing the imbalance of TREM2 and TLR4 and balancing the downstream NF-κB activation.

Topics: Animals; Biomarkers; Cell Line; Cell Polarity; Curcumin; Down-Regulation; Inflammation; Lipopolysaccharides; Membrane Glycoproteins; Mice; Microglia; NF-kappa B; Phenotype; Receptors, Immunologic; Signal Transduction; Toll-Like Receptor 4

Immunosuppression therapy is ineffective at preventing chronic rejection of lung allografts (bronchiolitis obliterans syndrome [BOS]) and proinflammatory cytokines by steroid-resistant lymphocytes. The class III NAD-sirtuin 1 (SIRT1) is an important negative regulator of inflammation; however, SIRT1 activity following lung transplant has not been studied. We hypothesized that SIRT1 expression is decreased in proinflammatory lymphocytes following lung transplant and that treatment with SIRT1 activators (resveratrol, curcumin) and agents that prevent NAD depletion (theophylline) upregulate SIRT1 and reduce proinflammatory cytokine expression in these cells.. Intracellular proinflammatory cytokines and SIRT1 were measured in blood T, natural killer T-like cell (NKT-like), and natural killer (NK) cells from patients with BOS (n = 10), stable lung transplant patients (n = 11), and healthy aged-matched controls (n = 10). Blood was cultured in the presence of ±25 µM resveratrol, ±1 µM curcumin, ±5 mg/L theophylline, ±1µM prednisolone and cytokines, and SIRT1 assessed using flow cytometry.. There was a loss of SIRT1 in T, NK-like, and NK cells in BOS patients compared with stable patients and controls (%CD8 SIRT1 T cells: 17 ± 10; 37 ± 10; 30 ± 10) (mean ± SEM BOS, stable, control, respectively) (P < 0.05 for all). Loss of SIRT1 was associated with increased T, NKT-like, and NK cells expressing interferon (IFN)γ and tumor necrosis factor (TNF)α. SIRT1 expression by T cells significantly associated with FEV1 (R = 0.655, P = 0.006) and with time posttransplant (R = -0.552, P = 0.041). All treatments upregulated SIRT1 and inhibited IFNγ and TNFα production by T, NK, and NKT-like cells additively.. BOS is associated with decreased SIRT1 in peripheral blood proinflammatory T, NK, and NKT-like lymphocytes following lung transplant. Treatment options that increase SIRT1 may improve graft survival.

Topics: Adult; Age Factors; Bronchiolitis Obliterans; Carbazoles; Case-Control Studies; Curcumin; Cytokines; Female; Graft Survival; Heterocyclic Compounds, 4 or More Rings; Humans; Immunosuppressive Agents; Inflammation; Interferon-gamma; Killer Cells, Natural; Lung Transplantation; Lymphocytes; Male; Middle Aged; Postoperative Complications; Prednisolone; Resveratrol; Sirtuin 1; T-Lymphocytes; Theophylline; Treatment Outcome

Topics: Administration, Oral; Animals; Apoptosis; Azoxymethane; Cell Cycle Checkpoints; Cell Line, Tumor; Cell Proliferation; Colitis; Colorectal Neoplasms; Curcumin; Cytokines; Dextran Sulfate; Disease Models, Animal; Disease Progression; Drug Synergism; Female; Inflammation; Inflammation Mediators; Intestines; Irinotecan; Macrophages; Mice; Mice, Inbred C57BL; Nanoparticles; RAW 264.7 Cells

Topics: Alzheimer Disease; Amyloid beta-Peptides; Animals; Antidepressive Agents; Antioxidants; Behavior Rating Scale; Catalase; Curcumin; Depression; Disease Models, Animal; Hippocampus; Inflammation; Male; Mice; Nanocapsules; Oxidative Stress; Peptide Fragments; Prefrontal Cortex; Superoxide Dismutase

VEGFR1 (Flt-1), is a high-affinity tyrosine kinase receptor of VEGF found primarily on vascular endothelial cells. Recently, Flt-1 has shown to be expressed in human monocytes. However, the key intracellular signaling pathway mediated by Flt-1 receptor has been yet to be identified in monocytes. In this regard, using a robust systems biology approach, the key druggable target(s) involved in inflammatory angiogenesis mediated through VEGFR1 signaling was identified. Furthermore, experimental validation of key drug targets is conducted using PMA- and VEGF- stimulated human monocyte THP-1 cell lines. The key network pathways and corresponding disease modules were analyzed to identify the important biological processes perturbed in diseases. Using topological analysis, ICAM1 was identified as putative regulator of monocytes migration into tumor-micro environment. And these targets were examined by treating with curcumin and capsaicin molecules. Our results showed that these two molecules inhibited the over expression of targets such as ICAM1, Flt-1, and NF-κB in the VEGFR1 signalling pathway by reducing THP-1 chemotaxis. Besides, Curcumin and Capsaicin down-regulated expression of pro-inflammatory cytokines TNF-α, IL-6, and CXCL8/IL-8 and up regulated the expression of IL-10, a sign of lowered M1/M2 ratio relating to abrogation of inflammation.

Topics: Capsaicin; Cell Movement; Curcumin; Cytokines; Down-Regulation; Humans; Inflammation; Monocytes; Systems Biology; THP-1 Cells

Anti-inflammatory proprieties of curcumin were proved to be useful in various diseases, including diabetes mellitus. The aim of this study was to assess the anti-inflammatory comparative effect of curcumin solution with liposomal curcumin formula, regarding the improvement of serum levels of TNF-α (tumor necrosis factor-alpha), IL-6 (interleukin), IL-1α, IL-1β, MCP-1 (monocyte chemoattractant protein-1) and RANTES in experimental diabetes, induced by streptozotocin (STZ), in rats.. Six groups of 7 rats were investigated regarding the effect of i.p. (intraperitoneal) administration of two concentrations of curcumin solution (CC1 and CC2) and two concentrations of liposomal curcumin (LCC1 and LCC2): group 1 - control group with i.p. administration of 1 mL saline solution, group 2 - i.p. STZ administration (60mg/kg bw, bw=body weight), group 3 - STZ+CC1 administration, group 4 - STZ+CC2 administration, group 5 - STZ+ LCC1 administration and group 6 - STZ+ LCC2 administration. The concentrations of curcumin formulas were 1 mg/0.1 kg bw for CC1 and LCC1 and 2 mg/0.1 kg bw for CC2 and LCC2, respectively. Serum levels of C-peptide (as an indicator of pancreatic function) and TNF-α, IL-6, IL-1α, IL-1β, MCP-1, and RANTES (as biomarkers for systemic inflammation) were assessed for each group.. The plasma level of C-peptide showed significant improvements when LCC was administrated, with better results for LCC2 when compared to LCC1 (P<0.003). LCC2 pretreatment proved to be more efficient in reducing the level of TNF-α (P<0.003) and RANTES (P<0.003) than CC2 pretreatment. Upon comparing LCC2 with LCC1 formulas, the differences were significant for TNF-α (P=0.004), IL-1β (P=0.022), and RANTES (P=0.003) levels.. Liposomal curcumin in a dose of 2 mg/0.1 kg bw proved to have an optimum therapeutic effect as a pretreatment in DM induced by STZ. This result can constitute a base for clinical studies for curcumin efficiency as adjuvant therapy in type 1 DM.

Topics: Animals; Anti-Inflammatory Agents; Biomarkers; Chemokine CCL2; Chemokine CCL5; Curcumin; Cytokines; Diabetes Mellitus, Experimental; Inflammation; Inflammation Mediators; Liposomes; Male; Rats; Streptozocin

Acute lung injury (ALI) is characterized by high prevalence and high mortality. Thus far, no effective pharmacological treatment has been made for ALI in clinics. Inflammation is critical to the development of ALI. Curcumin analog C66, having reported as an inhibitor of c-Jun N-terminal kinase (JNK), exhibits anti-inflammatory property both in vitro and in vivo. However, whether C66 is capable of reducing lipopolysaccharide (LPS)-induced ALI through the inhibition of inflammation by targeting JNK remains unknown.. Intratracheal injection of LPS was employed to build a mouse ALI model. H&E staining, wet/dry ratio, immunofluorescence staining, inflammatory cell detection, and inflammatory gene expression were used to evaluate lung injury and lung inflammation. In vitro, LPS was used to induce the expression of inflammatory cytokines both in protein and gene levels.. The results of our studies showed that the pretreatment with C66 and JNK inhibitor SP600125 was capable of attenuating the LPS-induced ALI by detecting pulmonary edema, pathological changes, total protein concentration, and inflammatory cell number in bronchoalveolar lavage fluid (BALF). Besides, C66 and SP600125 also suppressed LPS-induced inflammatory cytokine expression in BALF, serum, and lung tissue. In vitro, LPS-induced production of TNF-α and IL-6 and gene expression of TNF-α, IL-6, IL-1β, and COX-2 could be inhibited by the pretreatment with C66 and SP600125. It was found that C66 and SP600125 could inhibit LPS-induced phosphorylation of JNK both in vitro and in vivo.. In brief, our results suggested that C66 protects LPS-induced ALI through the inhibition of inflammation by targeting the JNK pathway. These findings further confirmed the pivotal role of JNK in ALI and implied that C66 is likely to serve as a potential therapeutic agent for ALI.

Topics: Acute Lung Injury; Animals; Anthracenes; Cells, Cultured; Curcumin; Disease Models, Animal; Dose-Response Relationship, Drug; Inflammation; Injections, Intravenous; JNK Mitogen-Activated Protein Kinases; Lipopolysaccharides; Male; Mice; Mice, Inbred C57BL; Molecular Structure; Phosphorylation; Structure-Activity Relationship

BACKGROUND Microglia reside in the spinal cord plays a key role in the onset, progression of post-spinal cord injury (SCI) neuroinflammation. Curcumin has been shown to exhibit diverse anti-inflammatory and anti-tumor activities. The aim of this study was to explore the effect of curcumin on the inflammatory response in lipopolysaccharide (LPS)-activated microglia and its mechanism. MATERIAL AND METHODS The expression levels of phosphorylated-p65 (p-p65), tumor necrosis factor (TNF)-alpha, interleukin (IL)-1ß, and IkappaB kinase ß (IKKß) were examined by western blot assay. MiR-199b-5p expression was detected by quantitative real-time polymerase chain reaction assay. The putative binding sites of miR-199b-5p in IKKß 3'UTR were predicted by bioinformatics, and direct interaction between miR-199b-5p and IKKß was verified by dual-luciferase reporter assay and RNA-immunoprecipitation assay. RESULTS Curcumin significantly suppressed inflammatory response induced by LPS by inactivation of nuclear factor kappa B (NF-kappaB) in microglial cells, as reflected by the decreased levels of p-p65, as well as the pro-inflammatory mediators, including inducible nitric oxide synthase (iNOS), TNF-alpha, and IL-1ß. Moreover, curcumin increased the level of miR-199b-5p and decreased IKKß expression in activated microglial cells. Knockdown of miR-199b-5p or overexpression of IKKß reversed the inhibitory effect of curcumin on inflammatory response and NF-kappaB activation. MiR-199b-5p directly targeted IKKß and suppressed its expression. Silencing of IKKß abolished miR-199b-5p-stimulated inflammatory cytokines production and NF-kappaB activation. CONCLUSIONS Curcumin attenuated neuroinflammation induced by LPS through regulating miR-199b-5p/IKKß/NF-kappaB axis in microglia.

Topics: Animals; Anti-Inflammatory Agents; Curcumin; I-kappa B Kinase; I-kappa B Proteins; Inflammation; Interleukin-1beta; Lipopolysaccharides; Mice; Microglia; MicroRNAs; Neuroimmunomodulation; NF-kappa B; NF-kappaB-Inducing Kinase; Nitric Oxide Synthase Type II; Protein Serine-Threonine Kinases; Signal Transduction; Spinal Cord Injuries; Transcription Factor RelA; Tumor Necrosis Factor-alpha

Topics: Curcumin; Humans; Inflammation; Mefenamic Acid; Molar; Molar, Third; Pain; Tooth Extraction; Tooth, Impacted

Endometriosis is a chronic gynecological inflammatory disorder in which immune system dysregulation is thought to play a role in its initiation and progression. Due to altered sex steroid receptor concentrations and other signaling defects, eutopic endometriotic tissues have an attenuated response to progesterone. This progesterone-resistance contributes to lesion survival, proliferation, pain, and infertility. The current agency-approved hormonal therapies, including synthetic progestins, GnRH agonists, and danazol are often of limited efficacy and counterproductive to fertility and cause systemic side effects due to suppression of endogenous steroid hormone levels. In the current study, we examined the effects of curcumin (CUR, diferuloylmethane), which has long been used as an anti-inflammatory folk medicine in Asian countries for this condition. The basal levels of proinflammatory and proangiogenic chemokines and cytokines expression were higher in primary cultures of stromal cells derived from eutopic endometrium of endometriosis (EESC) subjects compared with normal endometrial stromal cells (NESC). The treatment of EESC and NESC with CUR significantly and dose-dependently reduced chemokine and cytokine secretion over the time course. Notably, CUR treatment significantly decreased phosphorylation of the IKKα/β, NF-κB, STAT3, and JNK signaling pathways under these experimental conditions. Taken together, our findings suggest that CUR has therapeutic potential to abrogate aberrant activation of chemokines and cytokines, and IKKα/β, NF-κB, STAT3, and JNK signaling pathways to reduce inflammation associated with endometriosis.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Curcumin; Cytokines; Endometriosis; Endometrium; Female; Humans; Inflammation; NF-kappa B; Signal Transduction; Stromal Cells

Oral administrations of microparticles (MPs) and nanoparticles (NPs) have been widely employed as therapeutic approaches for the treatment of ulcerative colitis (UC). However, no previous study has comparatively investigated the therapeutic efficacies of MPs and NPs.. In this study, curcumin (CUR)-loaded MPs (CUR-MPs) and CUR-loaded NPs (CUR-NPs) were prepared using a single water-in-oil emulsion solvent evaporation technique. Their therapeutic outcomes against UC were further comparatively studied.. The resultant spherical MPs and NPs exhibited slightly negative zeta-potential with average particle diameters of approximately 1.7 µm and 270 nm, respectively. It was found that NPs exhibited a much higher CUR release rate than MPs within the same period of investigation. In vivo experiments demonstrated that oral administration of CUR-MPs and CUR-NPs reduced the symptoms of inflammation in a UC mouse model induced by dextran sulfate sodium. Importantly, CUR-NPs showed much better therapeutic outcomes in alleviating UC compared with CUR-MPs.. NPs can improve the anti-inflammatory activity of CUR by enhancing the drug release and cellular uptake efficiency, in comparison with MPs. Thus, they could be exploited as a promising oral drug delivery system for effective UC treatment.

Topics: Administration, Oral; Animals; Anti-Inflammatory Agents, Non-Steroidal; Cell-Derived Microparticles; Colitis, Ulcerative; Curcumin; Dextran Sulfate; Drug Carriers; Drug Delivery Systems; Female; Humans; Inflammation; Macrophages; Mice; Nanoparticles

CMC2.24, a novel tri-ketonic chemically modified compound based on natural di-ketonic curcumin, has been shown to reduce bone loss and inflammatory mediators in experimental periodontitis, however, a potential dose-response relationship was not determined. The purpose of this study was to assess the effects of different doses of CMC2.24 on inflammation and bone resorption in vivo and also to describe on the effects of CMC2.24 on macrophage response.. CMC2.24 was administered daily to animals for 28 days by oral gavage, at the following doses: 0 (control), 1, 3, 10, and 30 mg/kg of body weight. Experimental periodontitis was induced by injections of lipopolysaccharide (LPS) into the gingival tissues. Outcomes assessed were bone resorption, detection of tartrate-resistant acid phosphatase, and determination of gene expression. In vitro, macrophages (RAW264.7) were treated with different concentrations of CMC2.24: 1, 3, 10, and 30 μM and then subjected to different activation stimuli. Gene expression, phagocytic activity, production of reactive oxygen species (ROS) and cytokine production were evaluated.. CMC2.24 inhibited bone resorption, osteoclastogenesis, and tumor necrosis factor (TNF)-α expression in vivo. These beneficial responses reached maximum levels at a dose of 1 mg/kg, i.e. no dose-dependent effect. In vitro, CMC2.24 reduced the production of TNF-α and interleukin-10, inhibited phagocytic activity and stimulated production of ROS. A dose-dependent effect was observed only for ROS production.. Low doses of CMC2.24 (1 mg/kg/day) administered orally were sufficient to significantly inhibit alveolar bone resorption associated with the experimental periodontal disease; whereas in vitro macrophage inflammatory gene expression and phagocytosis were reduced, whereas production of ROS was stimulated.

Topics: Alveolar Bone Loss; Animals; Curcumin; Gingiva; Inflammation; Lipopolysaccharides; Osteoclasts; Periodontitis; Tumor Necrosis Factor-alpha

Bacterial infections can exacerbate asthmatic inflammation depending on lipopolysaccharide (LPS) composition, the outermost component of cell wall, its exposure timings as well as host's immune status. In present study, Balb/c mice were exposed to antigen (ovalbumin) and LPS simultaneously to establish an asthmatic model. Curcumin (diferuloylmethane), well known for its anti-inflammatory potential, was administered through intranasal route 1 h before LPS and OVA (ovalbumin) exposure to evaluate its efficacy against airway structural changes.. Inflammatory cell infiltration in lungs was measured by flow cytometry and further eosinophils were especially measured by immunofluorescence detection of major basic protein (MBP) as marker of eosinophilc granule protein. We also measured reactive oxygen species (ROS) in BALF by spectrofluorometry. MMP-9 activity was evaluated by gelatin zymography and mRNA expressions of MMP-9, TIMP-1, TGF-β1, IL-13, Collagen-1 and TLR-4 were measured in lungs. Protein expression of MAP kinases (P-ERK, P-JNK, P-p38), TLR-4, Cox-2, Lox-5 and Eotaxin was measured by western blotting. Hydroxyproline level and masson's trichrome staining were used to evaluate collagen deposition in lung.. Exposure to LPS (0.1 µg) exacerbates airway inflammation and induces structural changes in lungs by enhanced ROS production, collagen deposition, expression of genes involved in airway remodeling and activation of MAP kinases pathway enzymes. Intranasal curcumin pretreatment had significantly suppressed inflammatory mediators and airway remodeling proteins.. Our results strongly suggest that intranasal curcumin effectively protects LPS-induced airway inflammation and structural changes by modulating genes involved in airway remodeling in safer way; hence, it can be considered as supplementary alternative towards asthma treatments.

Topics: Administration, Intranasal; Airway Remodeling; Animals; Anti-Inflammatory Agents; Collagen; Curcumin; Disease Models, Animal; Inflammation; Lipopolysaccharides; Lung; Matrix Metalloproteinase 9; Mice; Mice, Inbred BALB C; Mitogen-Activated Protein Kinases; Ovalbumin; Protective Agents; Toll-Like Receptor 4

The ubiquitous use of diazinon (DZN, an organophosphorus insecticide) has increased the probability of occupational, public, and the ecosystem exposure; these exposures are linked to negative health outcomes. The flavonoids curcumin (CUR) and quercetin (QUE) exert significant anti-inflammatory and antioxidant activities against toxicants, including insecticides. However, it is unclear whether their combination enhances these activities. Therefore, 40 albino rat were divided randomly into the CTR, DZN, CUR + DZN, QUE + DZN, and CUR + QUE + DZN groups, which are treated daily via gavage for 28 days. DZN induced neurohepatic inflammation and oxidative damage, which was confirmed by significant (P < 0.05) induction of aspartate and alanine aminotransferases, alkaline phosphatase, lactate dehydrogenase, γ-glutamyl transferase, and tumor necrosis factor-α and inhibition of acetylcholinesterase activity. Furthermore, the liver and brain of DZN-exposed rats exhibited a notable elevation in MDA level paralleled with reduction in antioxidant molecules, i.e., glutathione, superoxide dismutase, glutathione peroxidase, and catalase. The pretreatment of DZN-intoxicated rats with CUR or QUE substantially mitigated neurohepatic dysfunction and inflammation and improved liver and brain antioxidant status with reducing oxidative stress levels. Furthermore, pretreatment with CUR + QUE synergistically restored the neurohepatic dysfunction and oxidative levels to approximately normal levels. The overall results suggested that CUR or QUE inhibits DZN-mediated neurohepatic toxicity via their favorable anti-inflammatory, antioxidant, and free radical-scavenging activities. Moreover, both QUE and CUR may be mutual adjuvant agents against oxidative stress neurohepatic damages.

Topics: Acetylcholinesterase; Animals; Antioxidants; Brain; Cholinesterase Inhibitors; Curcumin; Diazinon; Drug Synergism; Enzymes; Glutathione; Inflammation; Insecticides; Liver; Male; Oxidative Stress; Quercetin; Rats

Monosodium urate (MSU) crystals-induced inflammation is a key initiator in gouty arthritis. Curcumin is an active ingredient possessing anti-inflammatory efficacy. But the underlying mechanism is not fully understood and its effect on gouty arthritis remains elusive.. We evaluated the effects of curcumin on cell viability in primary rat abdominal macrophages with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT). Then supernatants of MSU crystals-stimulated cells were collected and subjected to enzyme-linked immunosorbent assay for checking the modulation of curcumin on interleukin (IL)-1β and tumor necrosis factor (TNF)-α. Meanwhile, cells were analyzed by using Western blot analysis and quantitative polymerase chain reaction (QPCR) to investigate the effects of curcumin on Nod-like receptor 3 (NLRP3) inflammasome/nuclear factor-kappa B (NF-κB) signaling. We also investigated the in vivo efficacy of curcumin with MSU-induced gouty arthritis rat models.. Curcumin could reduce MSU crystals-induced IL-1β and TNF-α in vitro. Western blot analysis and QPCR results revealed that curcumin regulated the production of these cytokines by suppressing the expression of inflammasome key components, including NLRP3, caspase-1. Further studies showed that the suppressive efficacy of curcumin on inflammasome was mediated by inhibiting MSU-induced NF-κB signaling activation. Intraperitoneal administration of curcumin could ameliorate symptoms of MSU-induced gouty arthritis, including the joint circumference, infiltration of neutrophils in knee joints, and production of IL-1β, TNF-α, and elastase. Western blot analysis revealed that the levels of NLRP3, procaspase-1, caspase-1, pro-IL-1β, and IL-1β were downregulated by curcumin in vivo.. These results indicated that curcumin could effectively ameliorate MSU crystal-induced gouty arthritis through NLRP3 inflammasome mediation via inhibiting NF-κB signaling both in vitro and in vivo, suggesting a promising active ingredient for the prevention and treatment of gouty arthritis.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Antioxidants; Arthritis, Gouty; Cell Proliferation; Curcumin; Cytokines; Female; Inflammasomes; Inflammation; Macrophages; Male; NF-kappa B; NLR Family, Pyrin Domain-Containing 3 Protein; Rats; Rats, Wistar; Signal Transduction; Uric Acid

BACKGROUND Periprosthetic osteolysis, induced by wear particles and inflammation, is a common reason for failure of primary arthroplasty. Curcumin, a nature phenol from plants, has been reported to reduce the inflammation in macrophages. This study aimed to investigate the potential effect of curcumin on macrophage involved, wear particle-induced osteolysis and its mechanism. MATERIAL AND METHODS RAW264.7 macrophages were used to test the effects of polyethylene (PE) particles and curcumin on macrophage cholesterol efflux and phenotypic changes. A mouse model of PE particle-induced calvarial osteolysis was established to test the effects of curcumin in vivo. After 14 days of treatment, the bone quality of the affected areas was analyzed by micro-computed tomography (micro-CT) and histology, and the bone surrounding soft tissues were analyzed at the cellular and molecular levels. RESULTS We found that PE particles can stimulate osteoclastogenesis and produce an M1-like phenotype in macrophages in vitro. Curcumin enhanced the cholesterol efflux in macrophages, and maintained the M0-like phenotype under the influence of PE particles in vitro. Additionally, the cholesterol transmembrane regulators ABCA1, ABCG1, and CAV1 were enhanced by curcumin in vivo. We also found enhanced bone density, reduced osteoclastogenesis, and fewer inflammatory responses in the curcumin treated groups in our mouse osteolysis model. CONCLUSIONS Our study findings indicated that curcumin can inhibit macrophage involved osteolysis and inflammation via promoting cholesterol efflux. Maintaining the cholesterol efflux might be a potential strategy to prevent periprosthetic osteolysis after total joint arthroplasty surgery.

Topics: Animals; Curcumin; Disease Models, Animal; Inflammation; Joint Prosthesis; Macrophages; Male; Mice; Mice, Inbred BALB C; Osteoclasts; Osteolysis; Polyethylene; Prosthesis Failure; RAW 264.7 Cells; Skull; X-Ray Microtomography

Hyperlipidemia is associated with endothelial dysfunction and inflammatory disorders. Adenosine and adenosine deaminase (ADA) modulate immune responses and lipid metabolism. Curcumin and rutin are polyphenols with antioxidant, anti-inflammatory, and hypolipidemic effects. We evaluated the action of rutin and curcumin in the lipid levels and inflammation, as well as their effect on ADA activity in serum, lymphocytes, platelets, and neutrophils of hyperlipidemic rats. Adult male Wistar rats pretreated with curcumin and/or rutin for 30 days were submitted to Poloxamer-407- induced hyperlipidemia. Biochemical, hematological, and oxidative stress parameters, as well as serum and extracellular ADA activity, were performed 36h post-induction. Hyperlipidemia was confirmed by the increase in total cholesterol (TC) and triglycerides (TG). Hematological alterations, elevated reactive oxygen species (ROS) levels, and increased myeloperoxidase (MPO) and ADA activities were observed in hyperlipidemic rats. Curcumin and the curcumin/rutin association decreased TG and increased high-density lipids (HDL) levels. The pretreatments prevented changes in the hematological parameters, decreased the activities of MPO in plasma and ADA in serum and cells. Cholesterol and ROS levels were not altered by the pretreatments. Our results show that pretreatments with rutin and/or curcumin prevent the hyperlipidemia-induced inflammation. Pretreatments with curcumin and/or rutin are potential complementary therapies in the prevention of hypertriglyceridemia and inflammation.

Topics: Adenosine Deaminase; Animals; Curcumin; Hyperlipidemias; Hypertriglyceridemia; Inflammation; Male; Oxidative Stress; Poloxamer; Rats; Rats, Wistar; Rutin; Triglycerides

Atherosclerosis is a major cardiovascular disease that causes ischemia of the heart, brain, or extremities, and can lead to infarction. The hypolipidemic agent atorvastatin calcium (Ato) alleviates atherosclerosis by reducing plasma lipid and inflammatory factors. However, the low bioavailability of Ato limits its widespread use and clinical effectiveness. Curcumin (Cur), a natural polyphenol with antioxidation and anti-inflammation bioactivities, has potential anti-atherosclerosis activity and may reduce Ato-induced cytotoxicity.. Liposomes modified using a targeting ligand (E-selectin-binding peptide) were prepared to co-deliver Ato and Cur to dysfunctional endothelial cells (ECs) overexpressing E-selectin. Molecules involved in the inhibition of adhesion (E-selectin and intercellular cell adhesion molecule-1 [ICAM-1]) and inflammation (IL-6 and monocyte chemotactic protein 1 [MCP-1]) in human aortic endothelial cells were evaluated using real-time quantitative PCR, flow cytometry, and immunofluorescence staining. The antiatherosclerosis effects of liposomes co-loaded with Ato and Cur in vivo were evaluated using ApoE knockout (ApoE. Targeted liposomes delivered Ato and Cur to dysfunctional ECs, resulting in synergistic suppression of adhesion molecules (E-selectin and ICAM-1) and plasma lipid levels. Moreover, this treatment reduced foam cell formation and the secretion of inflammatory factors (IL-6 and MCP-1) by blocking monocyte migration into the intima. In addition, Cur successfully reduced Ato-inducible cytotoxicity.. Both in vitro and in vivo experiments demonstrated that cell-targeted co-delivery of Ato and Cur to dysfunctional ECs drastically reduces atherosclerotic lesions with fewer side effects than either Ato or Cur alone.

Topics: Animals; Apolipoproteins E; Atherosclerosis; Atorvastatin; Cell Death; Cell Survival; Chemokine CCL2; Curcumin; Drug Synergism; E-Selectin; Endothelial Cells; Humans; Inflammation; Intercellular Adhesion Molecule-1; Interleukin-6; Ligands; Lipids; Liposomes; Mice, Knockout; Particle Size; Static Electricity

The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that integrates nutrients to execute cell growth. We hypothesized that mTOR is influential in the intervertebral disc-largest avascular, low-nutrient organ. Our objective was to identify the optimal mTOR inhibitor for treating human degenerative disc disease.. mTOR complex 1 (mTORC1) regulates p70/ribosomal S6 kinase (p70/S6K), negatively regulates autophagy, and is controlled by Akt. Akt is controlled by phosphatidylinositol 3-kinase (PI3K) and mTOR complex 2 (mTORC2). mTORC1 inhibitors-rapamycin, temsirolimus, everolimus, and curcumin, mTORC1&mTORC2 inhibitor-INK-128, PI3K&mTOR inhibitor-NVP-BEZ235, and Akt inhibitor-MK-2206-were applied to human disc nucleus pulposus (NP) cells. mTOR signaling, autophagy, apoptosis, senescence, and matrix metabolism were evaluated.. mTORC1 inhibitors decreased p70/S6K but increased Akt phosphorylation, promoted autophagy with light chain 3 (LC3)-II increases and p62/sequestosome 1 (p62/SQSTM1) decreases, and suppressed pro-inflammatory interleukin-1 beta (IL-1β)-induced apoptotic terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) positivity (versus rapamycin, 95% confidence interval (CI) -0.431 to -0.194; temsirolimus, 95% CI -0.529 to -0.292; everolimus, 95% CI -0.477 to -0.241; curcumin, 95% CI -0.248 to -0.011) and poly (ADP-ribose) polymerase (PARP) and caspase-9 cleavage, senescent senescence-associated beta-galactosidase (SA-β-gal) positivity (versus rapamycin, 95% CI -0.437 to -0.230; temsirolimus, 95% CI -0.534 to -0.327; everolimus, 95% CI -0.485 to -0.278; curcumin, 95% CI -0.210 to -0.003) and p16/INK4A expression, and catabolic matrix metalloproteinase (MMP) release and activation. Meanwhile, dual mTOR inhibitors decreased p70/S6K and Akt phosphorylation without enhanced autophagy and suppressed apoptosis, senescence, and matrix catabolism. MK-2206 counteracted protective effects of temsirolimus. Additional disc-tissue analysis found relevance of mTOR signaling to degeneration grades.. mTORC1 inhibitors-notably temsirolimus with an improved water solubility-but not dual mTOR inhibitors protect against inflammation-induced apoptosis, senescence, and matrix catabolism in human disc cells, which depends on Akt and autophagy induction.

Topics: Adult; Aged; Aged, 80 and over; Apoptosis; Autophagy; Benzoxazoles; beta-Galactosidase; Cellular Senescence; Curcumin; Everolimus; Extracellular Matrix; Female; Heterocyclic Compounds, 3-Ring; Humans; Imidazoles; Inflammation; Male; Matrix Metalloproteinases; Mechanistic Target of Rapamycin Complex 1; Mechanistic Target of Rapamycin Complex 2; Microtubule-Associated Proteins; Middle Aged; Nucleus Pulposus; Protein Kinase Inhibitors; Proto-Oncogene Proteins c-akt; Pyrimidines; Quinolines; Ribosomal Protein S6 Kinases, 70-kDa; Sequestosome-1 Protein; Sirolimus

This report focused on loading curcumin (CUR) drug into biodegradable Polylactide-poly(ethylene glycol) (PLA-PEG) copolymer nanoparticles as an effective anti-inflammatory agent in vivo to overcome the limitations resulted from the free CUR. By a simple nano-emulsification technique, hydrophobic CUR was loaded into hydrophobic polymer's segments and stabilized by cationic surfactant. They were then characterized by DLS, TEM, and SEM techniques providing monodispersed and spherical nanoparticles with an average diameter of 117 nm and high surface charge of +35 mV. Thereafter, they were orally administrated into five groups of rats, typically, control (healthy rats), streptozotocin (STZ)-induced diabetic rats, diabetics treated with free CUR, diabetics treated with PLA-PEG NPs, and diabetics treated with CUR-encapsulated PLA-PEG NPs. Next, complete blood analyses were assessed including alanine aminotransferase (ALT), aspartate aminotransferase (AST), and nuclear factor kappa B (NF-ҡB), reduced glutathione (GSH), malondialdehyde (MDA), nitric oxide (NO), cyclooxygenase (COX-2), Peroxisome proliferator-activated receptors (PPAR-γ) and transforming growth factor-β1 (TGF-β1). The obtained results demonstrated that diabetes initially produced liver inflammation in rats manifested by leveraging the mean levels of serum AST, ALT inducing oxidative stress resulting in a clear increase in the levels of hepatic MDA and NO concomitant with a remarkable decrease in GSH. Moreover, diabetes significantly increased serum NF-ҡB, hepatic COX-2 and TGF-β1, while highly reduced hepatic PPAR-γ. In contrast, both CUR free and CUR-encapsulated NPs ameliorated the negative changes in diabetes but CUR-encapsulated NPs showed more pronounced treated effect than free CUR. In addition, histopathological investigations were performed on the liver tissues of all groups, showing a mitigation in inflammation while treating with CUR-NPs.

Topics: Animals; Curcumin; Diabetes Mellitus, Experimental; Inflammation; Lactates; Liver; Male; Nanoparticles; Particle Size; Polyethylene Glycols; Rats; Streptozocin; Surface Properties

Atherosclerosis, a kind of peripheral arterial disease with chronic inflammation, leads to the dysfunction of the vascular system and many other diseases. Hypoxia has been proven to participate in the progression of atherosclerosis, while curcumin can inhibit hypoxia-inducible factor 1α (HIF-1α). However, the underlying mechanisms are still elusive.. qRT-PCR was used to examine the expression of HIF-1α, IL-6 and TNFα of macrophages under hypoxic condition. Western blot was applied to examine the changes of HIF-1α, ERK and p-ERK after treatment with curcumin. Oli Red O staining and enzymatic assay were used to examine the lipid and total cholesterol in macrophages, respectively. ELISA was used to examine the release of IL-6 and TNFα by macrophages. FACS and MTT assays were applied to examine the apoptosis and proliferation of macrophages.. Here, we found curcumin inhibited the expression of HIF-1α at the protein level in macrophages under hypoxic condition and curcumin and HIF-1α inhibitors repressed the total cholesterol and lipid level in macrophage under hypoxic condition. Moreover, curcumin also decreased the expression of HIF-1α downstream genes, VEGF, HMOX1, ROS and PDGF. Then, the data show the HIF-1α-induced apoptosis and inflammation of macrophages were inhibited by curcumin. Curcumin also rescued the proliferation defect of macrophages caused by hypoxia. Furthermore, we found it inhibited the expression of HIF-1α via ERK signaling pathway.. We describe that curcumin inhibited the HIF-1α-induced apoptosis and inflammation of macrophages via ERK signaling pathways. These results suggest curcumin can be used for the treatment of atherosclerosis.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Apoptosis; Cells, Cultured; Cholesterol; Curcumin; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Inflammation; Macrophages; MAP Kinase Signaling System; THP-1 Cells

Polyphenols are important immunonutrients which have been investigated in the context of inflammatory and autoimmune disease due to their significant immunosuppressive properties. However, the mechanism of action of many polyphenols is unclear, particularly in human immune cells. The emerging field of immunometabolism has highlighted the significance of metabolic function in the regulation of immune cell activity, yet the effects of polyphenols on immune cell metabolic signaling and function has not been explored. We have investigated the effects of two plant-derived polyphenols, carnosol and curcumin, on the metabolism of primary human dendritic cells (DC). We report that human DC display an increase in glycolysis and spare respiratory capacity in response to LPS stimulation, which was attenuated by both carnosol and curcumin treatment. The regulation of DC metabolism by these polyphenols appeared to be mediated by their activation of the cellular energy sensor, AMP-activated Protein Kinase (AMPK), which resulted in the inhibition of mTOR signaling in LPS-stimulated DC. Previously we have reported that both carnosol and curcumin can regulate the maturation and function of human DC through upregulation of the immunomodulatory enzyme, Heme Oxygenase-1 (HO-1). Here we also demonstrate that the induction of HO-1 by polyphenols in human DC is dependent on their activation of AMPK. Moreover, pharmacological inhibition of AMPK was found to reverse the observed reduction of DC maturation by carnosol and curcumin. This study therefore describes a novel relationship between metabolic signaling via AMPK and HO-1 induction by carnosol and curcumin in human DC, and characterizes the effects of these polyphenols on DC immunometabolism for the first time. These results expand our understanding of the mechanism of action of carnosol and curcumin in human immune cells, and suggest that polyphenol supplementation may be useful to regulate the metabolism and function of immune cells in inflammatory and metabolic disease.

Topics: Abietanes; AMP-Activated Protein Kinases; Cells, Cultured; Curcumin; Dendritic Cells; Heme Oxygenase-1; Humans; Immune System Phenomena; Inflammation; Metabolic Diseases; Polyphenols; Signal Transduction; TOR Serine-Threonine Kinases; Up-Regulation

Human infants or piglets are vulnerable to intestinal microbe-caused disorders and inflammation due to their rapidly changing gut microbiota and immaturity of their immune systems at weaning. Resveratrol and curcumin have significant anti-inflammatory, bacteria-regulating and immune-promoting effects. The purpose of this study was to investigate whether dietary supplementation with resveratrol and curcumin can change the intestinal microbiota and alleviate intestinal inflammation induced by weaning in piglets. One hundred eighty piglets weaned at 21 ± 2 d were fed a control diet (CON group) or supplemented diet (300 mg/kg of antibiotics, ANT group; 300 mg/kg of resveratrol and curcumin, respectively, HRC group; 100 mg/kg of resveratrol and curcumin, respectively, LRC group; 300 mg/kg of resveratrol, RES group; 300 mg/kg of curcumin, CUR group) for 28 days. The results showed that compared with the CON group, curcumin alone and antibiotics decreased the copy numbers of

Topics: Animals; Anti-Bacterial Agents; Bacteria; Biodiversity; Curcumin; Diet; Dietary Supplements; Female; Gastrointestinal Microbiome; Immunoglobulins; Inflammation; Interleukins; Male; Resveratrol; RNA, Messenger; Species Specificity; Swine; Toll-Like Receptor 4; Weaning

Inflammation and mitochondrial dysfunction have been linked to trauma, neurodegeneration, and aging. Impairment of CISD2 expression may trigger the aforementioned pathological conditions in neural cells. We previously reported that curcumin attenuates the downregulation of CISD2 in animal models of spinal cord injury and lipopolysaccharide (LPS)-treated neuronal cells. In this study, we investigate (1) the role of. The serial expression of CISD2 and the efficacy of curcumin treatment were evaluated in old (104 weeks) mice and long-term cultures of neural cells (35 days in vitro,. In the brain and spinal cord of mice aged P2, 8, 25, and 104 weeks, we observed a significant decrease in CISD2 expression with age. Curcumin treatment in vivo and in vitro was shown to upregulate CISD2 expression; attenuate inflammatory response in neural cells. Moreover, curcumin treatment elevated CISD2 expression levels and prevented mitochondrial dysfunction in LPS-challenged neural cells. The beneficial effects of curcumin in either non-stressed or LPS-challenged cells that underwent siCISD2 transfection were significantly lower than in respective groups of cells that underwent scrambled siRNA-transfection.. We hypothesize that the protective effects of curcumin treatment in reducing cellular inflammation associated trauma, degenerative, and aging processes can be partially attributed to elevated CISD2 expression. We observed a reduction in the protective effects of curcumin against injury-induced inflammation and mitochondrial dysfunction in cells where CISD2 expression was reduced by siCISD2.

Topics: Aging; Animals; Anti-Inflammatory Agents, Non-Steroidal; Apoptosis; Autophagy-Related Proteins; Carrier Proteins; Cell Line, Tumor; Cell Survival; Curcumin; Gene Expression Regulation; Gene Knockdown Techniques; Humans; Inflammation; Membrane Proteins; Mice; Mitochondria; Nerve Tissue Proteins; Real-Time Polymerase Chain Reaction; Reverse Transcriptase Polymerase Chain Reaction

Brachial plexus avulsion (BPA) generally causes a chronic persistent pain that lacks efficacious treatment. Curcumin has been found to possess anti-inflammatory abilities. However, little is known about the mechanisms and effects of curcumin in an animal model of BPA.. Mechanical withdrawal thresholds (MWT) were examined by von Frey filaments. Cold allodynia was tested by the acetone spray test. The levels of tumor necrosis factor-α (TNF-α) and interleukin (IL)-6 in rat spinal cords were analyzed by the enzyme-linked immunosorbent assay, and the expression levels of c-Fos and nerve growth factor (NGF) were measured by Western blot. The expression level of glial fibrillary acidic protein (GFAP) was observed by immunofluorescence and Western blot.. After curcumin treatment, the MWT showed a significant increase when compared to the BPA group on both hind paws. A remarkable decrease of paw-withdrawal response frequency was observed compared with the BPA group. In addition, curcumin treatment significantly decreased the levels of TNF-α and IL-6 in rat spinal cords that were exceedingly upregulated in the BPA group. The protein levels of c-Fos and NGF were decreased by treatment with curcumin compared with the corresponding protein levels in the BPA group. Besides, curcumin reduced the number of GFAP positive cells and GFAP expression.. Our findings suggest that curcumin significantly extenuates the BPA-induced pain and inflammation by reducing the expression level of proinflammatory cytokines and pain-associated proteins and inhibiting the activity of astrocytes.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Astrocytes; Blotting, Western; Brachial Plexus; Brachial Plexus Neuropathies; Curcumin; Cytokines; Disease Models, Animal; Fluorescent Antibody Technique; Glial Fibrillary Acidic Protein; Inflammation; Interleukin-6; Rats; Rats, Sprague-Dawley; Tumor Necrosis Factor-alpha

Both oxidative stress and inflammation contribute to the development of insulin resistance (IR). Curcumin (Cur) not only has an anti-inflammatory effect but also has an antioxidative stress effect via the activation of NF-E2-related factor 2 (Nrf2). Since there is close cross-communication between inflammation and oxidative stress, we examined whether Cur could modulate Nrf2 function via its anti-inflammatory ability and investigated its underlying mechanism. In this study, we show that Cur inhibits inflammatory signaling and Kelch-like ECH-associated protein 1 (Keap1) expression, which is accompanied by the activation of the Nrf2 system. We further identified that the proinflammatory cytokine tumor necrosis factor alpha (TNFα) could stimulate Keap1 synthesis and increase Nrf2 polyubiquitination, but these effects could be significantly inhibited by Cur treatment. This study demonstrates that Cur-induced Nrf2 activation occurs through the inhibition of inflammatory signaling-mediated upregulation of Keap1, contributing to its beneficial effects on redox homeostasis and insulin sensitivity.

Topics: Animals; Curcumin; Diet, High-Fat; Feeding Behavior; Glucose Tolerance Test; Hep G2 Cells; Humans; Inflammation; Insulin; Insulin Resistance; Kelch-Like ECH-Associated Protein 1; Male; Mice, Inbred C57BL; NF-E2-Related Factor 2; Proteasome Endopeptidase Complex; Proteolysis; RNA, Messenger; Signal Transduction; Up-Regulation

Background Curcumin is extensively used as a therapeutic intervention for treating several ailments. The antioxidant curcumin has an anti-inflammatory and chelating property with arsenic to exhibit a strong therapeutic effect on reproductive organs. This study was undertaken to describe the protective effect of noninvasive administration of curcumin against sodium-arsenite-mediated uterine hazards in female Wistar rats. Methods Twenty-four female Wistar rats were randomly divided into four groups. The treatment was continued for 8 days and given orally sodium arsenite (10 mg/kg body weight) in combination with curcumin (20 mg/kg body weight). Results Our evaluation revealed that 8 days of sodium arsenite (10 mg/kg body weight) treatment reduced the activities of the uterine enzymatic antioxidants superoxide dismutase, catalase, and peroxidase. Blood levels of vitamin B12 and folic acid decreased followed by an increased serum lactate dehydrogenase, homocysteine level, and hepatic metallothionein-1 in arsenic-treated rats. Necrosis of uterine tissue along with the disruption of ovarian steroidogenesis was marked in arsenic-treated rats with an upregulation of uterine NF-κB and IL-6 along with a raised level of serum TNF-α. Oral administration of curcumin (20 mg/kg body weight/day) in arsenic-treated rats significantly reinstated these alterations of the antioxidant system followed by an improvement of ovarian steroidogenesis and the circulating level of B12 and folate along with the downregulation of serum homocysteine, metallothionein-1, and cytokines. Conclusions The findings of this study clearly and strongly elucidated that arsenic-induced oxidative stress in uterus is linked to an alteration of inflammation-signaling biomarkers and these have been protected through the co-administration of curcumin due to its anti-inflammatory, free radical scavenging, and antioxidant activity by the possible regulation of an S-adenosine methionine pool.

Topics: Animals; Antioxidants; Arsenic; Arsenites; Catalase; Curcumin; Cytokines; Female; Glutathione; Glutathione Peroxidase; Inflammation; Metallothionein; NF-kappa B; Oxidative Stress; Peroxidase; Rats; Rats, Wistar; Sodium Compounds; Superoxide Dismutase; Uterus

This study aimed to determine the capacity of 7,7'-bromo-curcumin (CUR-Br), a curcumin analogue with higher chemical stability than curcumin (CUR), in the suppression of mouse ear edema. Male CD-1 mice were topically pre-treated with either CUR or CUR-Br for 30 min prior to an application of 12-O-tetradecanoylphorbol-13-acetate. After 6 h, mice were killed, and ear punches were measured for their weight and thickness as a marker of edema and inflammation. CUR-Br demonstrated a higher anti-inflammatory efficacy compared to CUR. CUR and CUR-Br at 1.0 μmol suppressed the TPA-induced increase in the ear weight by 26.0% and 57.2%, and decreased TPA-induced increase in the ear thickness by 22.2% and 84.7%, respectively. The inhibitory effects of Cur-Br were associated with decreased levels of inflammatory cytokines (IL-1β, IL-2, IL-6, KC/GRO, IL-10, IL-17, and IL-23). In addition, CUR-Br significantly downregulated expression of pro-inflammatory signaling proteins such as p-STAT3, STAT3, PI3K, AKT, p-p65, and COX-2. Overall, our results demonstrated that the curcumin analogue, CUR-Br, showed stronger anti-inflammatory properties than CUR in inhibiting TPA-induced inflammatory response in mouse skin.

Topics: Animals; Curcumin; Cytokines; Edema; Inflammation; Male; Mice; NF-kappa B; Signal Transduction; Skin; STAT3 Transcription Factor; Structure-Activity Relationship; Tetradecanoylphorbol Acetate

Topics: Angiogenesis Inducing Agents; Animals; Anti-Inflammatory Agents, Non-Steroidal; Chitosan; Curcumin; Diabetes Mellitus, Experimental; Drug Carriers; Human Umbilical Vein Endothelial Cells; Humans; Inflammation; Nanoparticles; Rats; Rats, Sprague-Dawley; Wound Healing

BACKGROUND Curcumin is an antioxidant that reduces inflammation and pain. This study aimed to assess the effect of pretreatment with naproxen and liposomal curcumin compared with naproxen and curcumin solution on oxidative stress parameters and pain in a rat model of migraine. MATERIAL AND METHODS Sixty-three male Wistar rats included a control group (n=9) and a rat model of migraine (n=54) induced by intraperitoneal injection of nitroglycerin (1 mg/0.1 kg). The rat model group was divided into an untreated control group (n=9), a group pretreated with naproxen alone (2.8 mg/kg) (n=9), a group pretreated with naproxen (2.8 mg/kg) combined with curcumin solution (1 mg/0.1 kg) (n=9), a group pretreated with naproxen (2.8 mg/kg) combined with curcumin solution (2 mg/0.1 kg) (n=9), a group pretreated with naproxen (2.8 mg/kg) combined with liposomal curcumin solution (1 mg/0.1 kg) (n=9) a group pretreated with naproxen (2.8 mg/kg) combined with liposomal curcumin solution (2 mg/0.1 kg) (n=9). Spectroscopy measured biomarkers of total oxidative status and nociception was tested using an injection of 1% of formalin into the rat paw. RESULTS Expression of biomarkers of oxidative stress and enhanced nociception were significantly increased following pretreatment with combined naproxen and liposomal curcumin compared with curcumin solution or naproxen alone (P<0.001). Combined curcumin solution and naproxen were more effective at a concentration of 2 mg/0.1kg for the first nociceptive phase (P<0.005). CONCLUSIONS In a rat model of migraine, combined therapy with liposomal curcumin and naproxen showed an improved antioxidant effect and anti-nociceptive effect.

Topics: Animals; Antioxidants; Curcumin; Disease Models, Animal; Drug Therapy, Combination; Inflammation; Male; Migraine Disorders; Naproxen; Oxidative Stress; Pain; Pain Measurement; Rats; Rats, Wistar

Current evidences suggest that hyperuricemia is closely related to the overproduction or underexcretion of uric acid (UA). Curcumin (CUR), a natural polyphenol component extracted from the rhizome of Curcuma longa, has been reported to treat various symptoms such inflammation disease, seems to be efficacious in hyperuricemia. In this study, we aimed to investigate the effect of CUR on hyperuricemia and kidney inflammation in hyperuricemic mice. Administration with CUR (20 or 40 mg/kg) or allopurinol (ALL, 5 mg/kg) was given to mice orally one hour later after the injection of potassium oxonate (PO) (300 mg/kg, i.p.) for 14 days. CUR administration decreased the levels of uric acid (UA), creatinine (CRE) and blood urea nitrogen (BUN) in serum. Meanwhile, treatment with CUR effectively inhibited serum and liver xanthine oxidase (XOD) levels, and further renewed normal antioxidant enzymes activities (SOD, GSH-Px), reduced MDA accumulation in serum. Further studies showed that CUR decreased inflammatory cytokines productions (IL-1β, IL-18) in serum, as well as inhibited PO-induced the activation of NLRP3 inflammasome signaling in the kidney. In conclusion, the study revealed that CUR exhibited anti-hyperuricemic and anti-inflammatory effects through suppressing NLRP3 inflammasome activation in kidney and provided the evidence for treating hyperuricemia and associated renal inflammation.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Antioxidants; Biomarkers; Curcumin; Cytokines; Disease Models, Animal; Hyperuricemia; Inflammasomes; Inflammation; Kidney; Kidney Function Tests; Male; Mice, Inbred Strains; NLR Family, Pyrin Domain-Containing 3 Protein; Oxonic Acid

The efficacy of the plant-derived polyphenol curcumin, in various aspects of health and wellbeing, are a matter of public interest. An internet search of the term "Curcumin" displays about 12 million hits. Among the multitudinous information presented on partly doubtful websites, there are reports attracting the reader with promises ranging from eternal youth to cures for incurable diseases. Unfortunately, many of these reports are not based on scientific evidence, but they feed the desideratum of the reader for a "miracle cure". This circumstance makes it very difficult for researchers, whose work is scientifically sound and evidence is based on the therapeutic benefits (or side effects) of curcumin, to demarcate their results from sensational reports that circulate in the web and in other media. This is only one of many obstacles making it difficult to pave curcumin's way into clinical application; others are its nonpatentability and low economic usability. A further impediment comes from scientists who never worked with curcumin or any other natural plant-derived compound in their own labs. They have never tested these compounds in any scientific assay, neither in vitro nor in vivo; however, they claim, in a sometimes polemic manner, that everything that has so far been published on curcumin's molecular effects is based on artefacts. The here presented Special Issue comprises a collection of five scientifically sound articles and nine reviews reporting on the therapeutic benefits and the molecular mechanisms of curcumin or of chemically modified curcumin in various diseases ranging from malignant tumors to chronic diseases, microbial infection, and even neurodegenerative diseases. The excellent results of the scientific projects that underlie the five original papers give reason to hope that curcumin will be part of novel treatment strategies in the near future-either as monotherapy or in combination with other drugs or therapeutic applications.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Antineoplastic Agents; Curcumin; Humans; Infections; Inflammation; Neoplasms; Neurodegenerative Diseases; Neuroprotective Agents

Chronic inflammation depends on inflammatory mediators produced by activated macrophages and is the common pathological basis for various diseases. Turmeronol is a sesquiterpenoid found in the spice turmeric (Curcuma longa), which is known to have anti-inflammatory activity. To elucidate the anti-inflammatory mechanism of turmeronol, we investigated the influence of turmeronol A and turmeronol B in mouse macrophages (RAW264.7 cells) stimulated with lipopolysaccharide (LPS). Pretreatment of RAW264.7 cells with either turmeronol A or B significantly inhibited LPS-induced production of prostaglandin E

Topics: Animals; Anti-Inflammatory Agents; Curcuma; Dinoprostone; Inflammation; Inflammation Mediators; Interleukin-6; Lipopolysaccharides; Macrophages; Mice; NF-kappa B; Nitric Oxide; Plant Extracts; RAW 264.7 Cells; Sesquiterpenes; Tumor Necrosis Factor-alpha

Inflammation is the key mediator for arthritis. Plant based products are most useful for treating various disorders, but at the same time drug absorption is utmost important for effective therapy. The present aim of our study was to find out the therapeutic concern in pharmacokinetic and pharmacodynamic parameters in an arthritis induced rat model.. Carregenan and complete Freud's adjuvant, both were used for an arthritis induction as an animal model. Formulation of curcumin was prepared in different quality of milk brand, high fat milk with ghee and in an aqueous suspension. They were administered orally to the rats for 21 days continuously. Different pharmacodyanmic parameters were analyzed which include percentage inhibition of inflammation, cytokines (IL-6 and TNF-α), hematological levels, X-Rays and histology condition. Pharmacokinetics was also determined like Cmax, Tmax and Kel using HPLC method.. The result concludes that, curcumin in full fat milk with ghee and full fat curcumin formulation treated group showed a higher statistical significant effect in the prevention of inflammation in both the models. The presence of curcumin in plasma was higher only in full fat with ghee formulation and full fat milk formulation treated group when compared to the other groups.. Hence, it concludes that the presence of adjuvant act as an enhancer can increase the bioavailability of curcumin for achieving maximum effectiveness.

Topics: Animals; Anti-Inflammatory Agents; Arthritis, Experimental; Curcumin; Cytokines; Disease Models, Animal; Female; Freund's Adjuvant; Inflammation; Interleukin-6; Male; Milk; Rats; Tumor Necrosis Factor-alpha

Non-alcoholic fatty liver disease (NAFLD) is characterized by hepatic macrophage inflammation, steatosis and fibrosis. Liposomes injected intravenously passively target hepatic myeloid cells and have potential to deliver immunomodulatory compounds and treat disease. We investigated targeting, delivery, immunomodulation and efficacy of liposomes in mice with diet-induced NASH.. Liposome-encapsulated lipophilic curcumin or 1,25-dihydroxy-vitamin D3 (calcitriol) were injected intravenously into mice with diet-induced NASH. Liver and cell liposome uptake was assessed by in vivo imaging and flow cytometry. Immunomodulation of targeted cells were assessed by RNA transcriptome sequencing. NASH was assessed by histological scoring, serum liver enzymes and fasting glucose/insulin and liver RNA transcriptome sequencing.. Liposomes targeted lipid containing MHC class-II. Liposomes are a new strategy to target lipid rich inflammatory dendritic cells and have potential to deliver immunomodulatory compounds to treat NASH.

Topics: Animals; Curcumin; Diet, High-Fat; Disease Progression; Female; Fibrosis; Hepatocytes; Immunologic Factors; Inflammation; Insulin Resistance; Liposomes; Liver; Liver Cirrhosis; Macrophages; Mice; Mice, Inbred C57BL; Non-alcoholic Fatty Liver Disease; Transcriptome; Vitamin D

The current study introduces a new idea of utilising several bio/chemoinformatics tools in comparing two bio-similar natural molecules viz. curcumin and bisdemethoxycurcumin (BDMC) in order to select a potential nose-to-brain remedy for Alzheimer disease. The comparison comprised several bio/chemo informatics tools. It encompassed all levels starting from loading the drug in a certain carrier; PLGA nanoparticles, to the biopharmaceutical level investigating the interaction with mucin and inhibition of P-gp blood-brain barrier efflux pumps. Finally, the therapeutic level was investigated by studying the interaction with pharmacological targets such as amyloid peptide plaques and cyclooxygenase2 enzyme responsible for the inflammatory reactions of the studied disease. The comparison revealed the superiority of curcumin over BDMC. Five new analogues were also hypothesised where diethoxybisdemethoxycurcumin was  recommended as a superior molecule. This work introduced the virtual utilisation of bio/chemo informatics tools as a reliable and economic alternative to the exhausting and resources-consuming wet-lab experimentation.

Topics: Alzheimer Disease; ATP Binding Cassette Transporter, Subfamily B; Brain; Computational Biology; Curcumin; Diarylheptanoids; Drug Carriers; Humans; Inflammation; Mucins; Nose

Endothelial cell inflammatory injury is likely required for barrier dysfunction under hyperglycemic conditions. Curcumin (CUR) is well known for its anti-inflammatory effect. However, there have been few reports about the anti-inflammatory effect of CUR induced by high glucose in endothelial cells. The aim of the present study was to investigate the inflammatory effect of high glucose and the anti-inflammatory effect of CUR induced by high glucose in rat thoracic aorta endothelial cells (TAECs).. Well characterized TAECs were established and cell viability was assayed by the cell counting kit-8 method, messenger ribonucleic acid and protein expression were identified by real-time polymerase chain reaction, western blot or enzyme-linked immunosorbent assay, respectively. The production of reactive oxygen species was observed by a fluorescence microscope.. High glucose (30 mmol/L) significantly decreased the cell viability of TAECs after being co-cultivated for 12 h and showed a time-dependent manner, and increased interleukin (IL)-1β, IL-6 and tumor necrosis factor-α secretion in TAECs. The injury effect of high glucose was involved in the reactive oxygen species-phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)-nuclear factor (NF)-κB signaling pathway. Anti-oxidant N-acetylcysteine, PI3K and NF-κB-specific pathway inhibitors can abolish the secretion of these inflammatory factors; pretreatment with anti-oxidant N-acetylcysteine significantly decreased PI3K expression, the level of phosphorylated AKT and nuclear NF-κB; pretreatment of LY294002 can significantly decrease the NF-κB level in nuclei. After treatment with CUR for 12 h, IL-1β, IL-6 and tumor necrosis factor-α secretion were markedly decreased, and PI3K expression, the phosphorylation of AKT and nuclear NF-κB level were also decreased.. Curcumin attenuates high glucose-induced inflammatory injury through the reactive oxygen species-PI3K/AKT-NF-κB signaling pathway in rat thoracic aorta endothelial cells.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Aorta, Thoracic; Cell Survival; Curcumin; Cytokines; Endothelial Cells; Glucose; Inflammation; Male; NF-kappa B; Phosphatidylinositol 3-Kinase; Proto-Oncogene Proteins c-akt; Rats, Sprague-Dawley; Reactive Oxygen Species; Signal Transduction

Inflammation‑associated damage may occur in any tissue following infection, exposure to toxins, following ischemia, and in allergic and auto‑immune reactions. Inflammation may also result from mast cell degranulation induced by the intracellular calcium concentration. The inflammatory process may be inhibited by compounds that affect mast cells. Bisdemethoxycurcumin [1,7‑bis(4‑hydroxyphenyl) hepta‑1,6‑diene‑3,5‑dione, BDCM] is the active component of turmeric. It has anticancer, antioxidant and antibacterial properties. To investigate the molecular mechanism associated with the anti‑inflammatory activity of BDCM, human mast cell line 1 (HMC‑1) cells were treated with phorbol‑12‑myristate‑13‑acetate (PMA) and calcium ionophore A23187 (A23187) to induce the inflammatory process. Various HMC‑1 cells were pretreated with BDCM prior to stimulation of inflammation. BDCM inhibited the inflammation‑triggered production of cytokines including interleukin (IL)‑6, IL‑8, and tumor necrosis factor (TNF)‑α. BDCM inhibition extended to the gene level. In activated HMC‑1 cells, phosphorylation levels of extracellular signal‑regulated kinase, c‑jun N‑terminal kinase and p38 mitogen‑activated protein kinase were decreased by treatment with BDCM. BDCM also inhibited nuclear factor‑(NF)‑κB activation and IκB degradation. In conclusion, BDCM suppresses the expression of TNF‑α, IL‑8, and IL‑6 by inhibiting the NF‑κB and mitogen activated protein kinase signaling pathways.

Topics: Calcimycin; Cell Line; Curcumin; Diarylheptanoids; Gene Expression Regulation; Humans; Inflammation; Mast Cells; Mitogen-Activated Protein Kinase Kinases; NF-kappa B; Signal Transduction; Tetradecanoylphorbol Acetate; Transcription Factor RelA

Curcumin is the main curcuminoid present in Curcuma longa and it has been previously reported to exhibit a wide range of pharmacological activities. In the present study, the inhibitory effects of curcumin on the inflammatory mediators released by Pam3CSK4-stimulated BV-2 microglial cells were investigated. The production of pro-inflammatory mediators and cytokines, including tumor necrosis factor-α (TNF-α) and prostaglandin E2 (PGE2), were measured by enzyme‑linked immunosorbent assay (ELISA). The expression of inflammatory genes, including inducible nitric oxide synthase and cyclooxygenase-2, were further investigated using reverse transcription-quantitative polymerase chain reaction. The effects of curcumin on heme oxygenase-1 (HO-1), nuclear factor (erythroid-derived 2)-like 2 (Nrf2), mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) signaling pathways were analyzed by western blotting. The results revealed that curcumin dose-dependently inhibited Pam3CSK4-induced nitric oxide, PGE2, and TNF-α secretion. Curcumin suppressed the secretion of inflammatory mediators through an increase in the expression of HO-1. Curcumin induced HO-1 transcription and translation through the Nrf2/antioxidant response element signaling pathway. Inhibitory experiments revealed that HO-1 was required for the anti-inflammatory effects of curcumin. Further mechanistic studies demonstrated that curcumin inhibited neuroinflammation by suppressing NF-κB and MAPK signaling pathways in Pam3CSK4-activated microglial cells. The results of the present study suggest that curcumin may be a novel treatment for neuroinflammation-mediated neurodegenerative disorders.

Topics: Antioxidant Response Elements; Cell Line; Curcumin; Dinoprostone; Gene Expression Regulation; Heme Oxygenase-1; Humans; Inflammation; Lipopeptides; MAP Kinase Kinase 1; Microglia; Neurodegenerative Diseases; NF-E2-Related Factor 2; Nitric Oxide; Signal Transduction; Tumor Necrosis Factor-alpha

Targeting inflammatory macrophages and their products is an effective method for controlling inflammation. The pyrazole analog of curcumin (curcumin pyrazole, PYR) has been reported to possess superior anti-inflammatory activity to curcumin (CUR). However, the role of PYR anti-inflammatory activity in macrophages has not yet been elucidated.. To examine the anti-inflammatory effects of PYR and CUR in lipopolysaccharide (LPS)-activated RAW 264.7 macrophages and determine the role of mitogen-activated protein kinases (MAPK) in their activity.. Nitrite level was investigated by the Griess assay. The expression of inducible nitric oxide (NO) synthase, cyclooxygenase-2 (COX-2), and MAPK proteins were analyzed by western blot analysis. The pro-inflammatory cytokines tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and interleukin-6 (IL-6) were measured by enzyme-linked immunosorbent assay.. LPS-induced NO secretion in RAW 264.7 macrophages was potently inhibited by PYR (IC50 = 3.7 ± 0.16 μM), at a higher efficacy than CUR (IC50 = 11.0 ± 0.59 μM). Treatment with identical concentrations of PYR and CUR demonstrated that PYR drastically inhibited iNOS and COX-2 expression, whereas CUR only blocked COX-2. PYR reduced the LPS-induced secretion of TNF-α to a greater extent than CUR and both similarly reduced IL-1β and IL-6 levels. Activation of c-Jun N-terminal kinase (JNK) MAPK was significantly decreased in LPS-activated RAW 264.7 macrophages upon PYR but not CUR treatment.. PYR exhibited a more potent anti-inflammatory activity than CUR. This activity is partly mediated by PYR-depended inhibition of the JNK signaling pathway and underscores the utility of PYR as an anti-inflammatory agent in macrophages.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Curcumin; Enzyme Activation; Inflammation; Lipopolysaccharides; Macrophages; MAP Kinase Signaling System; Mice; Pyrazoles; RAW 264.7 Cells

Nutriosomes, new phospholipid nanovesicles specifically designed for intestinal protection were developed by simultaneously loading a water-soluble dextrin (Nutriose® FM06) and a natural antioxidant (curcumin). Nutriosomes were easily fabricated in a one-step, organic solvent-free procedure. The stability and delivery performances of the vesicles were improved by adding hydroxypropyl methylcellulose. All the vesicles were small in size (mean diameter ∼168 nm), negatively charged (zeta potential ∼-38 mV, irrespective of their composition), and self-assembled predominantly in unilamellar vesicles stabilized by the presence of Nutriose®, which was located in both the inter-lamellar and inter-vesicle media, as confirmed by cryo-TEM and SAXS investigation. The dextrin acted also as a cryo-protector, avoiding vesicle collapse during the lyophilization process, and as a protector against high ionic strength and pH changes encountered in the gastrointestinal environment. Thanks to the antioxidant properties of curcumin, nutriosomes provided an optimal protective effect against hydrogen peroxide-induced oxidative stress in Caco-2 cells. Moreover, these innovative vesicles showed promising efficacy in vivo, as they improved the bioavailability and the biodistribution of both curcumin and dextrin upon oral administration, which acted synergically in reducing colonic damage chemically induced in rats.

Topics: Animals; Biological Availability; Caco-2 Cells; Cryoprotective Agents; Curcumin; Dextrins; Drug Delivery Systems; Freeze Drying; Humans; Inflammation; Intestines; Male; Microscopy, Electron, Transmission; Oxidative Stress; Phospholipids; Prebiotics; Rats; Rats, Wistar; Scattering, Small Angle; Tissue Distribution; X-Ray Diffraction

Effects of curcumin, a major ingredient of turmeric, were tested on the function of the

Topics: Allosteric Regulation; alpha7 Nicotinic Acetylcholine Receptor; Animals; Benzamides; Bridged Bicyclo Compounds; Curcumin; Disease Models, Animal; Female; Inflammation; Male; Mice; Motor Activity; Nociception; Pain

Studies have shown that satins and herbal products have potential to treat non-alcohol fatty liver disease (NAFLD) in clinic. However, no study has compared their effects, and their mechanisms remain unresolved. Here, we choose lovastatin and two herbal products including berberine and curcumin to compare their effects in treating NAFLD. NAFLD model was established by high fat food, and rats were administrated with lovastatin, berberine, curcumin, berberine + curcumin at the dosage of 100, 100, 100, 50 + 50 mg/kg bw, respectively. The body weight, visceral fat gain, histological inspection and serum parameters were studied to exam the curative effects. In addition, mediators including SREBP-1c, caveolin-1, pERK, NF-κB, TNF-α, and pJNK were studied. Results showed that berberine + curcumin group exhibited lower body and fat weigh compared with lovastatin group. Biochemical assays showed that LDL-c, ALT, AST, ALP, MDA, LSP level were lower in berberine + curcumin group compared with lovastatin group. Lower expression of SREBP-1c, pERK, TNF-α, and pJNK were also observed in berberine + curcumin group. We conclude that combination of curcumin and berberine exhibited better ameliorative effects in treating NAFLD than lovastatin, and this enhanced effect is associated with oxidative stress, hepatic inflammation and lipid metabolism.

Topics: Alanine Transaminase; Alkaline Phosphatase; Animals; Aspartate Aminotransferases; Berberine; Biological Products; Blood Glucose; Body Weight; Curcumin; Gene Expression Regulation; Inflammation; Insulin; Intra-Abdominal Fat; Lipid Metabolism; Lipids; Lipopolysaccharides; Liver; Lovastatin; Male; Non-alcoholic Fatty Liver Disease; Organ Size; Oxidative Stress; Rats, Sprague-Dawley

Vascular endothelial dysfunction is a potential risk factor for cardiovascular disease. This study evaluated the effect of curcumin on factors associated with vascular dysfunction using rats fed a high-sucrose, high-fat (HSF) diet. The experiment included 2 animal feeding phases. In the first feeding phase, male Sprague-Dawley rats were randomly divided into 2 groups: the control group (n = 8) was fed a standard diet (AIN-93G) and the HSF group (n = 24) was fed an HSF diet for 8 weeks to induce obesity. In the second feeding phase, lasting 4 weeks, the HSF group was randomly divided into 3 subgroups: the O group (n = 8) continued feeding on the HSF diet, the OA group (n = 8) had the HSF diet replaced with AIN-93G, and the OC group (n = 8) was fed the HSF diet supplemented with curcumin (300 mg/kg body weight daily). After 8 weeks, the HSF diet significantly elevated levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), insulin, homeostatic model assessment insulin resistance (HOMA-IR), low-density lipoprotein cholesterol (LDL-C), homocysteine (Hcy), C-reactive protein (CRP), vascular cell adhesion molecule 1 (VCAM-1), and intercellular adhesion molecule 1 (ICAM-1) but significantly reduced levels of nitric oxide (NO) and high-density lipoprotein cholesterol (HDL-C). After dietary intervention, the OA and OC groups exhibited significantly lower levels of AST, ALT, HOMA-IR, cholesterol, LDL-C, Hcy, CRP, VCAM-1, and ICAM-1 and higher levels of NO and catalase (CAT) activity compared with the O group. Superoxide dismutase, CAT, and glutathione peroxidase activities were increased in the OA group, while CAT levels were enhanced in the OC group. In conclusion, this study showed that curcumin supplementation and diet modification can inhibit HSF diet-induced vascular dysfunction potentially by enhancing NO production and antioxidant enzyme activities, thereby suppressing inflammation and oxidative damage in the vascular endothelium.

Topics: Alanine Transaminase; Animals; Antioxidants; Aspartate Aminotransferases; Biomarkers; C-Reactive Protein; Cholesterol; Curcumin; Diet, High-Fat; Dietary Sucrose; Endothelium, Vascular; Homocysteine; Inflammation; Insulin; Insulin Resistance; Intercellular Adhesion Molecule-1; Liver; Male; Malondialdehyde; Obesity; Oxidative Stress; Rats; Rats, Sprague-Dawley; Risk Factors; Vascular Cell Adhesion Molecule-1; Vascular Diseases

The present study was aimed to investigate the effect of diet derived AGEs (dAGEs) on the circulatory levels of pro-inflammatory cytokines, chemokines and to evaluate the protective efficacy of natural anti-oxidants curcumin (CU) and gallic acid (GA) respectively against the dAGEs-induced systemic inflammation in experimental Swiss albino mice. The experimental mice were fed with dAGEs in the presence and absence of CU and GA for 6 months. The levels of 40 circulatory pro-inflammatory cytokines and chemokines were evaluated using Proteome-Cytokine Array kit. In addition, serum levels of N-ɛCML, CRP and HbA1c were estimated by ELISA method. Among the sixteen pro- and anti-inflammatory cytokines analysed, five (IL-16, IL-1α, ICAM, TIMP-1 and C5a) were found to be highly expressed (3.5-fold) and eleven cytokines were moderately expressed (2-fold) in dAGEs fed mice. In case of chemokines, three (BLC, SDF-1 and MCP-1) were found to be highly expressed (4-fold) and ten showed moderate expression (2-fold) as compared with basal diet fed mice. Interestingly, CU or GA co-treatment normalized the levels of circulatory pro- and anti-inflammatory cytokines, chemokines, N-ɛCML, CRP and HbA1c levels. Together, the present study suggests that dAGEs are positively associated with the development of systemic inflammation in experimental mice.

Topics: Animals; Anti-Inflammatory Agents; Chemokines; Curcumin; Cytokines; Diet; Gallic Acid; Glycation End Products, Advanced; Humans; Inflammation; Male; Mice; Protective Agents; Weight Gain

Diminished cognitive and mood function are among the most conspicuous symptoms of Gulf War Illness (GWI). Our previous studies in a rat model of GWI have demonstrated that persistent cognitive and mood impairments are associated with substantially declined neurogenesis, chronic low-grade inflammation, increased oxidative stress and mitochondrial dysfunction in the hippocampus. We tested the efficacy of curcumin (CUR) to maintain better cognitive and mood function in a rat model of GWI because of its neurogenic, antiinflammatory, antioxidant, and memory and mood enhancing properties. Male rats were exposed daily to low doses of GWI-related chemicals, pyridostigmine bromide, N,N-diethyl-m-toluamide (DEET) and permethrin, and 5-minutes of restraint stress for 28 days. Animals were next randomly assigned to two groups, which received daily CUR or vehicle treatment for 30 days. Animals also received 5'-bromodeoxyuridine during the last seven days of treatment for analysis of neurogenesis. Behavioral studies through object location, novel object recognition and novelty suppressed feeding tests performed sixty days after treatment revealed better cognitive and mood function in CUR treated GWI rats. These rats also displayed enhanced neurogenesis and diminished inflammation typified by reduced astrocyte hypertrophy and activated microglia in the hippocampus. Additional studies showed that CUR treatment to GWI rats enhanced the expression of antioxidant genes and normalized the expression of multiple genes related to mitochondrial respiration. Thus, CUR therapy is efficacious for maintaining better memory and mood function in a model of GWI. Enhanced neurogenesis, restrained inflammation and oxidative stress with normalized mitochondrial respiration may underlie better memory and mood function mediated by CUR treatment.

Topics: Affect; Animals; Anti-Inflammatory Agents, Non-Steroidal; Cognition; Curcumin; DEET; Disease Models, Animal; Hippocampus; Inflammation; Male; Mitochondria; Neurogenesis; Oxidative Stress; Permethrin; Persian Gulf Syndrome; Rats

Emerging treatment options for colon cancer are needed to overcome the limitations regarding the side effects of current chemotherapeutics and drug resistance. The goal of this study was to assess the antitumor actions of PEGylated long-circulating liposomes (LCL) co-delivering curcumin (CURC) and doxorubicin (DOX) on murine colon carcinoma cells (C26).. The cytotoxicity of CURC and DOX, administered alone or in combination, either in free or LCL form, was evaluated with regard to antiproliferative effects on C26 cells and to protumor processes that might be affected.. Our results indicated that PEGylated LCL-CURC-DOX exerted strong antiproliferative effects on C26 cells, slightly exceeding those induced by free CURC-DOX, but higher than either agent administered alone in their free form. These effects of LCL-CURC-DOX were due to the inhibition of the production of angiogenic/inflammatory proteins in a NF-κB-dependent manner, but were independent of ROS production or AP-1 c-Jun activation. Notable, the anti-angiogenic actions of LCL-CURC-DOX appeared to be much stronger than those induced by the co-administration of CURC and DOX in their free form, on C26 colon cancer cells.. LCL-CURC-DOX demonstrated enhanced cytotoxicity on C26 murine colon cancer cells by inhibiting the production of the majority of factors involved in tumor-associated angiogenesis and inflammation and is now being evaluated in vivo regarding its efficacy towards tumor growth in colon cancer.

Topics: Angiogenesis Inhibitors; Animals; Anti-Inflammatory Agents; Antineoplastic Agents; Apoptosis; Cell Line, Tumor; Colon; Colonic Neoplasms; Curcumin; Doxorubicin; Drug Resistance, Neoplasm; Inflammation; Liposomes; Mice; Neovascularization, Pathologic; NF-kappa B; Polyethylene Glycols; Proto-Oncogene Proteins c-jun; Reactive Oxygen Species; Transcription Factor AP-1

Cyclo-oxygenase-2 (COX2) plays a prominent role in carcinogenesis. This study addresses the effects of two nutraceutical compounds on the expression of COX2 and tumor-associated inflammation in human papillomavirus type 16 (HPV16)-transgenic mice.. Six-week-old FVB/n mice were supplemented with rutin or curcumin for 24 weeks: HPV16. Rutin reduced COX2 expression in the dermis (immunostaining score 7.83 versus 11.25 in untreated HPV16-transgenic mice) and epidermis (4.5 versus 10.0). Curcumin led to dermal and epidermal scores of 10.5 and 4.5. Both compounds reduced leukocytic infiltration, but neither prevented epidermal dysplasia.. COX2 expression in HPV16-induced lesions may be modulated by nutraceuticals, reducing tumor-associated inflammation. However, this was not sufficient to block carcinogenesis, calling for additional studies focused on combination therapies.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Curcumin; Cyclooxygenase 2; Disease Progression; Down-Regulation; Female; Human papillomavirus 16; Humans; Inflammation; Leukocytes; Mice, Transgenic; Papillomavirus Infections; Rutin; Skin; Skin Neoplasms

Curcumin has been introduced as effective anti-inflammatory agent in treatment of several inflammatory disorders. Despite the wide range pharmacological activities, clinical application of curcumin is restricted mainly due to the low water solubility of this substance. More recently, we could remarkably improve the aqueous solubility of curcumin by its encapsulation in chitosan-alginate-sodium tripolyphosphate nanoparticles (CS-ALG-STPP NPs). In this study, the anti-inflammatory and myelin protective effects of curcumin-loaded NPs were evaluated in lysolecithin (LPC)-induced focal demyelination model. Pharmacokinetic of curcumin was assessed using high performance liquid chromatography (HPLC). Local demyelination was induced by injection of LPC into corpus callosum of rats. Animals were pre-treated with intraperitoneal (i.p.) injections of curcumin or curcumin-loaded NPs at dose of 12.5 mg/kg, 10 days prior to LPC injection and the injections were continued for 7 or 14 days post lesion. Hematoxylin and eosin (H&E) staining and immunostaining against activated glial cells including astrocytes and microglia were carried out for assessment of inflammation level in lesion site. Myelin specific staining was performed to evaluate the effect of curcumin-loaded NPs on myelination of LPC receiving animals. HPLC results showed the higher plasma concentration of curcumin after administration of NPs. Histological evaluation demonstrated that, the extent of demyelination areas was reduced in animals under treatment of curcumin-loaded NPs. Furthermore, treatment with curcumin-loaded NPs effectively attenuated glial activation and inflammation in LPC-induced demyelination model compared to curcumin receiving animals. Overall; these findings indicate that treatment with curcumin-loaded NPs preserve myelinated axons through amelioration of glial activation and inflammation in demyelination context.

Topics: Animals; Anti-Inflammatory Agents; Corpus Callosum; Curcumin; Demyelinating Diseases; Disease Models, Animal; Drug Delivery Systems; Inflammation; Lysophosphatidylcholines; Male; Myelin Sheath; Nanoparticles; Neuroglia; Rats, Wistar

Inflammation is highly associated with colon carcinogenesis. Epigenetic mechanisms could play an important role in the initiation and progression of colon cancer. Curcumin, a dietary phytochemical, shows promising effects in suppressing colitis-associated colon cancer in azoxymethane-dextran sulfate sodium (AOM-DSS) mice. However, the potential epigenetic mechanisms of curcumin in colon cancer remain unknown. In this study, the anticancer effect of curcumin in suppressing colon cancer in an 18-week AOM-DSS colon cancer mouse model was confirmed. We identified lists of differentially expressed and differentially methylated genes in pairwise comparisons and several pathways involved in the potential anticancer effect of curcumin. These pathways include LPS/IL-1-mediated inhibition of RXR function, Nrf2-mediated oxidative stress response, production of NO and ROS in macrophages and IL-6 signaling. Among these genes, Tnf stood out with decreased DNA CpG methylation of Tnf in the AOM-DSS group and reversal of the AOM-DSS induced Tnf demethylation by curcumin. These observations in Tnf methylation correlated with increased and decreased Tnf expression in RNA-seq. The functional role of DNA methylation of Tnf was further confirmed by in vitro luciferase transcriptional activity assay. In addition, the DNA methylation level in a group of inflammatory genes was decreased in the AOM+DSS group but restored by curcumin and was validated by pyrosequencing. This study shows for the first time epigenomic changes in DNA CpG methylation in the inflammatory response from colitis-associated colon cancer and the reversal of their CpG methylation changes by curcumin. Future clinical epigenetic studies with curcumin in inflammation-associated colon cancer would be warranted.

Topics: Animals; Azoxymethane; Colitis; Colon; Colonic Neoplasms; Curcumin; Dextran Sulfate; Disease Models, Animal; DNA Methylation; Epigenesis, Genetic; Inflammation; Male; Mice; Mice, Inbred C57BL; Oxidative Stress; Transcriptome

A large proportion of Gulf War Veterans suffer from Gulf War Illness (GWI) - a devastating chronic disorder characterized by heterogeneous fatigue, pain and neuropsychological symptoms. In their recent Brain, Behavior and Immunity publication entitled "Curcumin Treatment Leads to Better Cognitive and Mood Function in a Model of Gulf War Illness with Enhanced Neurogenesis, and Alleviation of Inflammation and Mitochondrial Dysfunction in the Hippocampus", Kodali and colleagues (2018) report that the polyphenol curcumin improves cognition and mood in a rat model of GWI, potentially by increasing the expression of antioxidant genes and by reversing the effects of chronic combined acetylcholinesterase inhibitor exposure on neuroinflammation, mitochondrial respiration and hippocampal neurogenesis. This preclinical work is encouraging for our veterans who suffer chronically from GWI as well as for developing strategies to protect our troops during future deployments in similar environments.

Topics: Animals; Cognition; Curcumin; Gulf War; Hippocampus; Inflammation; Mitochondria; Neurogenesis; Persian Gulf Syndrome; Rats; Veterans

The purpose of this study was to compare the effects of the oral administration of natural curcumin and a chemically modified curcumin (CMC2.24) on osteoclast-mediated bone resorption, apoptosis, and inflammation in a murine model of experimental periodontal disease.. Fifty male rats were distributed among the following treatment groups: (i) 2% carboxymethylcellulose, (ii) CMC2.24 30 mg/kg body weight, (iii) Curcumin 100 mg/kg body weight and (iv) no treatment. Compounds were administered daily by oral intubation over a 15-day period of time. Periodontal disease was induced by injections of LPS (lipopolysaccharide) into the gingival tissues three times per week. Contralateral sides were injected with the same volume of PBS (phosphate buffered saline) vehicle. After 15 days, hemimaxillae and gingival tissues were harvested. Bone resorption was assessed by μCT (microcomputer tomography). Formalin-fixed, paraffin embedded histological sections were stained with haematoxylin/eosin (H/E) for the assessment of cellular infiltrate or subjected to immunohistochemistry for detecting TRAP (tartrate-resistant acid phosphatase)-positive cells and caspase-3. Apoptosis was assessed in the gingival tissues by DNA fragmentation.. CMC2.24 and curcumin caused a significant reduction of the inflammatory cell infiltrate, however μCT analysis showed that only CMC2.24 reduced bone resorption and the number of TRAP-positive multinucleated cells (osteoclasts). Curcumin, but not CMC2.24, significantly reduced the number of apoptotic cells in the gingival tissues and of osteocytes in the alveolar bone crest.. The results suggest that CMC2.24 and curcumin inhibit inflammation by different mechanisms, but only CMC2.24 was capable of reducing alveolar bone resorption in the LPS-induced model of periodontitis.

Topics: Administration, Oral; Alveolar Bone Loss; Animals; Apoptosis; Body Weight; Bone and Bones; Carboxymethylcellulose Sodium; Caspase 3; Curcumin; Disease Models, Animal; Gingiva; Immunohistochemistry; Inflammation; Lipopolysaccharides; Male; Osteoclasts; Periodontitis; Rats; Tartrate-Resistant Acid Phosphatase; Time Factors; Tomography

There is evidence indicating that curcumin has multiple biological activities, including anti-inflammatory properties. In vitro and in vivo studies demonstrate that curcumin may attenuate inflammation and the connective tissue destruction associated with periodontal disease. Most of these studies use systemic administration, and considering the site-specific nature of periodontal disease and also the poor pharmacodynamic properties of curcumin, we conducted this proof of principle study to assess the biological effect of the local administration of curcumin in a nanoparticle vehicle on experimental periodontal disease. We used 16 rats divided into two groups of 8 animals according to the induction of experimental periodontal disease by bilateral injections of LPS or of the vehicle control directly into the gingival tissues 3×/week for 4 weeks. The same volume of curcumin-loaded nanoparticles or of nanoparticle vehicle was injected into the same sites 2×/week. µCT analysis showed that local administration of curcumin resulted in a complete inhibition of inflammatory bone resorption and in a significant decrease of both osteoclast counts and of the inflammatory infiltrate; as well as a marked attenuation of p38 MAPK and NF-kB activation. We conclude that local administration of curcumin-loaded nanoparticles effectively inhibited inflammation and bone resorption associated with experimental periodontal disease.

Topics: Administration, Topical; Animals; Anti-Inflammatory Agents, Non-Steroidal; Blotting, Western; Bone Resorption; Curcumin; Disease Models, Animal; Histocytochemistry; Inflammation; Injections; Nanoparticles; Periodontal Diseases; Rats; Treatment Outcome; X-Ray Microtomography

Aberrant succinate accumulation emerges as a unifying mechanism for inflammation and oxidative stress. This study aims to investigate whether curcumin ameliorates hepatic fibrosis via blocking succinate signaling.. We investigated the effects of curcumin on hepatic succinate accumulation and liver fibrosis in mice fed a high-fat diet (HFD). Meanwhile, we stimulated mouse primary hepatic stellate cells (HSCs) with succinate and observed the inhibitory effects of curcumin on succinate signaling.. Oral administration of curcumin and metformin combated mitochondrial fatty acid oxidation and reduced hepatic succinate accumulation due to the inhibition of succinate dehydrogenase (SDH) activity and demonstrated inhibitory effect on hepatic fibrosis. In mouse primary HSCs, curcumin prevented succinate- and CoCl. Hepatic succinate accumulation served as a metabolic signal to promote liver fibrosis through HIF-1α induction. Curcumin reduced succinate accumulation by combating fatty acid oxidation and prevented HSCs activation by blocking succinate/HIF-1α signaling pathway.

Topics: Animals; Curcumin; Diet, High-Fat; Hepatic Stellate Cells; Hypoxia-Inducible Factor 1, alpha Subunit; Inflammation; Liver Cirrhosis; Male; Mice, Inbred ICR; Models, Biological; Succinic Acid

Sepsis is characterized by the extensive release of cytokines and other mediators. It results in a dysregulated immune response and can lead to organ damage and death. Curcumin has anti-inflammatory properties and immunoregulation functions in various disorders such as sepsis, cancer, rheumatoid arthritis, cardiovascular diseases, lung fibrosis, gallstone formation, and diabetes. This paper investigates the effects of curcumin on immune status and inflammatory response in mice subjected to cecal ligation and puncture (CLP). Inflammatory tissue injury was evaluated by histological observation. Magnetic microbeads were used to isolate splenic CD4

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Cecum; Cells, Cultured; Curcumin; Disease Models, Animal; Forkhead Transcription Factors; Humans; Immunomagnetic Separation; Immunosuppression Therapy; Inflammation; Interleukin-10; Kidney; Lung; Male; Mice; Mice, Inbred BALB C; Neutrophil Infiltration; Sepsis; T-Lymphocytes, Regulatory

To examine whether curcumin has protective effect on insulin resistance induced by bisphenol A (BPA) in LO2 cells and whether this effect was mediated by inhibiting the inflammatory mitogen-activated protein kinases (MAPKs) and nuclear factor-κB (NF-κB) pathways.. LO2 cells were stimulated with BPA in the presence or absence of curcumin for 5 days. Glucose consumption, activation of insulin signaling, MAPKs and NF-κB pathways, levels of inflammatory cytokines and MDA production were analyzed.. Curcumin prevented BPA-induced reduction of glucose consumption and suppression of insulin signaling pathway, indicating curcumin alleviated BPA-triggered insulin resistance in LO2 cells. mRNA and proteins levels of TNF-α and IL-6, as well as MDA level in LO2 cells treated with BPA were decreased by curcumin. Furthermore, curcumin downregulated the activation of p38, JNK, and NF-κB pathways upon stimulation with BPA. Inhibition of JNK pathway, but not p38 nor NF-κB pathway, improved glucose consumption and insulin signaling in BPA-treated LO2 cells.. Curcumin inhibits BPA-induced insulin resistance by suppressing JNK pathway.

Topics: Anthracenes; Benzhydryl Compounds; Cell Line; Curcumin; Enzyme Activation; Humans; Imidazoles; Inflammation; Insulin Resistance; MAP Kinase Signaling System; NF-kappa B; Oxidative Stress; Phenols; Pyridines; Pyrrolidines; Thiocarbamates

Curcumin is a polyphenol compound with many pharmacological activities including antioxidant, lipid-loweing and liver protective. Dihydrocurcumin (DHC) is one of the major metabolites of curcumin. So far, the pharmacological activity of DHC has not been reported. Here, we evaluate the effects of DHC on oleic acid (OA)-induced lipid accumulation, oxidative stress and insulin resistance and the underlying mechanism in L02 and HepG2 cells.. OA-induced L02 and HepG2 cells were used as the in vitro model of nonalcoholic fatty liver disease (NAFLD). Lipid accumulation, oxidative stress, glucose uptake and cell inflammation were evaluated by cellular biochemical assay, respectively. Signaling pathways involved in lipid metabolism including peroxisome proliferator activated receptor-α (PPARα), the sterol regulatory element binding protein-1C (SREBP-1C) and patatin-like phospholipase domain containing 3 (PNPLA3), glucose uptake including phosphatidylinositol 3-kinase (PI3K) and phosphorylated serine-threonine protein kinase (pAKT), and oxidative stress including nuclear factor E2-related factor 2 (Nrf2), cytochrome P450 4A (CYP4A) and 2E1 (CYP2E1) were investigated by western blotting and RT-qPCR, respectively.. DHC decreased the levels of cellular triglycerides (TG) by regulating the mRNA and protein expression levels of SREBP-1C, PNPLA3 and PPARα. At the same time, DHC improved the hepatocellular glucose uptake by increasing the protein expression levels of pAKT and PI3K. Furthermore, DHC reduced the levels of cellular NO and ROS via Nrf2 signaling pathways.. The present study firstly revealed that DHC ameliorated OA-induced steatosis through regulating the lipid metabolism, oxidative stress and insulin resistance in HepG2 and L02 cells.

Topics: Cell Death; Cell Survival; Curcumin; Gene Expression Regulation; Glucose; Hep G2 Cells; Humans; Inflammation; Insulin Resistance; Lipid Metabolism; Nitric Oxide; Oleic Acid; Oxidative Stress; Phosphatidylinositol 3-Kinases; Phosphorylation; Proto-Oncogene Proteins c-akt; Reactive Oxygen Species; RNA, Messenger; Signal Transduction; Triglycerides

Warburg effect is characterized by the upregulation of HIF-1 and c-Myc regulated LDH-A, even aerobically owing to hypoxic environment and alterations in oncogenes or tumor suppressor genes in cancer. Reduced antioxidant defence system in transformed cells favors higher ROS production, which plays a significant role in carcinogenesis and acts as an important regulator of NF-κB. In addition, various proinflammatory cytokines play active roles in maintenance and progression of cancer.. In continuation with our previous studies illustrating the long-term effect of curcumin using a liver tissue, present study was aimed to elucidate the anti-cancer effect of curcumin due to its long-term effect in the regulation of glycolytic metabolism, NF-κB activation, expression of proinflammatory cytokines in Dalton's lymphoma ascites cells in vivo.. Spectrophotometric assays, RT-PCR and EMSA were performed to address the problems.. Results revealed that curcumin-induced activation of antioxidant enzymes, Nrf2 and downstream signaling gene NQO1. Reduction of oxidative stress, down-regulation of NADPH: Oxidase, decline in ROS and H2O2 levels were also observed. Activation of NF-κB, expression of COX2, HIF-1α and cMyc, as well as expression and activity of LDH-A were significantly reduced by curcumin. Besides, expression of proinflammatory cytokines was significantly down-regulated via reducing binding of nuclear protein with AP-1, NF-IL6, ETS and NF-κB binding elements of IL-1α, IL-1β, TNF-α and IL-6 promoters, respectively.. Curcumin downregulates glycolytic metabolism via modulation of stress-activated genes and reduces oxidative stress by enhancing antioxidant defence system, which inhibits activation of NF-κB signaling and expression of proinflammatory cytokines in Dalton's lymphoma ascites cells in vivo.

Topics: Animals; Antineoplastic Agents; Ascites; Curcumin; Cytokines; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; Glucose; Glycolysis; Inflammation; Lymphoma; Male; Mice; Mice, Inbred AKR; Mice, Inbred DBA; Molecular Structure; NF-E2-Related Factor 2; Structure-Activity Relationship

Chronic inflammation is a key driver of cancer development. Nitrite levels, which are regulated by inducible nitric oxide synthase (iNOS), play a critical role in inflammation. While the anti-oxidant and anti-inflammatory effects of curcumin, a natural product present in the roots of Curcuma longa have been studied widely, the acute pharmacokinetics (PK) and pharmacodynamics (PD) of curcumin in suppressing pro-inflammatory markers and epigenetic modulators remain unclear. This study evaluated the PK and PD of curcumin-induced suppression of lipopolysaccharide (LPS)-mediated inflammation in rat lymphocytes. LPS was administered intravenously either alone or with curcumin to female Sprague-Dawley rats. Plasma samples were analysed for curcumin concentration and mRNA expression was quantified in lymphocytes. The relative gene expression of several inflammatory and epigenetic modulators was analysed. To investigate the relationship between curcumin concentration and iNOS, TNF-α, and IL-6 gene expression, PK/PD modeling using Jusko's indirect response model (IDR) integrating transit compartments (TC) describing the delayed response was conducted. The concentration-time profile of curcumin exhibited a bi-exponential decline, which was well described by a two-compartmental pharmacokinetic model. Importantly the results demonstrate that LPS induced gene expression of pro-inflammatory markers in lymphocytes, with peak expression at approximately 3 h and curcumin suppressed the gene expression in animals administered with LPS. These effects were well captured using the IDR model and an IDR model with the transit compartments. In summary, the PK/PD modeling approach could potentially provide a robust quantitative framework for evaluating the acute anti-inflammatory and epigenetic effects of curcumin in future clinical trials.

Topics: Animals; Anti-Inflammatory Agents; Curcumin; Epigenesis, Genetic; Female; Gene Expression Regulation; Inflammation; Rats; Rats, Sprague-Dawley; RNA, Messenger

Recent studies have strongly indicated the hepatoprotective effect of curcumin; however, the precise mechanisms are not well understood. This study aimed to determine the protective effect of curcumin on hepatic damage and hepatic insulin resistance in biliary duct ligated (BDL) fibrotic rat model. To accomplish this, male Wistar rats were divided into four groups (eight for each): sham group, BDL group, sham+Cur group and BDL+Cur group. The last two groups received curcumin at a dose of 100 mg/kg daily for 4 weeks. The mRNA/protein expression levels of Ras-related C3 botulinum toxin substrate 1 (Rac1), Rac1-GTP, dinucleotide phosphate oxidase 1 (NOX1), signal transducer and activator of transcription 3 (STAT3), suppressor of cytokine signalling 3 (SOCS3), insulin receptor substrate 1 (IRS1), extracellular signal-regulated kinase 1 (ERK1), specific protein 1 (Sp1) and hypoxia-inducible factor-1α (HIF-1α) were measured by real-time PCR and Western blotting, respectively. Fasting blood glucose, insulin and Leptin levels were determined and homoeostasis model assessment-estimated insulin resistance, as an index of insulin resistance, was calculated. Curcumin significantly attenuated liver injury and fibrosis, including amelioration of liver histological changes, reduction of hepatic enzymes, as well as decreased expression of liver fibrogenesis-associated variables, including Rac1, Rac1-GTP, NOX1, ERK1, HIF-1α and Sp1. Curcumin also attenuated leptin level and insulin resistance, which had increased in BDL rats (P<0·05). Furthermore, compared with the BDL group, we observed an increase in IRS1 and a decrease in SOCS3 and STAT3 expression in the curcumin-treated BDL group (P<0·05), indicating return of these parameters towards normalcy. In conclusion, Curcumin showed hepatoprotective activity against BDL-induced liver injury and hepatic insulin resistance by influencing the expression of some genes/proteins involved in these processes, and the results suggest that it can be used as a therapeutic option.

Topics: Animals; Bile Ducts; Curcumin; Gene Expression Profiling; Homeostasis; Hypoxia-Inducible Factor 1, alpha Subunit; Inflammation; Insulin Receptor Substrate Proteins; Insulin Resistance; Ligation; Liver Cirrhosis; Male; Malondialdehyde; Mitogen-Activated Protein Kinase 3; NADPH Oxidase 1; rac1 GTP-Binding Protein; Rats; Rats, Wistar; STAT3 Transcription Factor

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease, which can cause endless suffering to the patients and severely impact their normal lives. To treat RA, the drugs in use have many serious side effects, high cost, or only focus on their anti-inflammatory mechanisms without taking joint lubrication into consideration. Therefore, in this study, we aim to construct a novel anti-RA drug composed of hyaluronic acid/curcumin (HA/Cur) nanomicelle to resolve these problems. Characterizations show that Cur is bound to HA by ester linkages and self-assembles to form a spherical nanomicelle with a diameter of around 164 nm under the main driving of the hydrophilic and hydrophobic forces. The nanomicelle enjoys excellent biocompatibility that effectively promotes the proliferation of chondrocytes. When injected to the RA rats, the nanomicelle significantly lowers the edema degree of the arthritic rats compared to other groups; more critically, a dramatic decrease in friction between the surfaces of cartilage around the joints has been found, which protects the cartilage from the RA-induced damage. Additionally, systematic mechanism investigation indicates that the nanomicelle diminishes the expression of related cytokines and vascular endothelial growth factor, finally leading to the excellent performance. The newfound nanomicelle has a potential for clinical practice of RA therapy, which will contribute significantly to alleviating the pain of patients and improving the quality of life for them.

Topics: Animals; Arthritis, Rheumatoid; Curcumin; Hyaluronic Acid; Inflammation; Lubrication; Quality of Life; Rats; Vascular Endothelial Growth Factor A

Allergic asthma is an inflammatory condition accompanied by inflammation as well as oxidative stress. Supplementation of an anti-inflammatory agent having antioxidant properties may have therapeutic effects against this disease. Over the recent decades, the interest in combination therapy as new alternative medication has increased and it offers numerous benefits along with noticeable lack of toxicity as well as side effects. In this study, protective effects of curcumin alone and in combination with piperine were evaluated in mouse model of allergic asthma. Balb/c mice were sensitized on days 0, 7, and 14 and challenged from days 16-30 on alternate days with ovalbumin (OVA). Mice were pretreated with curcumin (Cur; 10 and 20 mg/kg) and piperine (Pip; 5 mg/kg) alone and in combination via the intraperitoneal route on days 16-30 and compared with intranasal curcumin (5 mg/kg) treatment. Blood, bronchoalveolar lavage fluid (BALF), and lungs were collected after mice were sacrificed on day 31st. Mice immunized with OVA have shown significant increase in airway inflammation and oxidative stress as determined by oxidative stress markers. A significant suppression was observed with all the treatments, but intranasal curcumin treatment group has shown maximum suppression. So, among all the treatment strategies utilized, intranasal curcumin administration was most appropriate in reducing inflammation and oxidative stress and possesses therapeutic potential against allergic asthma. Present study may prove the possibility of development of curcumin nasal drops towards treatment of allergic asthma.

Topics: Alkaloids; Animals; Anti-Inflammatory Agents; Asthma; Benzodioxoles; Bronchoalveolar Lavage Fluid; Curcumin; Drug Administration Routes; Drug Therapy, Combination; Inflammation; Lung; Mice; Mice, Inbred BALB C; Ovalbumin; Oxidative Stress; Piperidines; Polyunsaturated Alkamides

The purpose of this study is to evaluate the therapeutic effects of curcumin on airway inflammation using LPS and cigarette smoke (LC)-induced COPD murine models and LPS-stimulated human bronchial epithelial (BEAS-2B) cells. In this research, COPD murine models were established after challenged with LPS for 2 days and exposed to cigarette smoke for 35 days. Treatment with curcumin for 10 days distinctly alleviated airway inflammation and airway remolding in LC-induced COPD mice according to the lung H&E histopathological examination. The number of neutrophils and lymphocytes in broncho alveolar lavage fluid (BALF) was significantly decreased in curcumin+LC-treated group compared with the LC-induced mice. Additionally, curcumin inhibited BEAS-2B cells proliferation, which suggested the preventive effect of curcumin on progressive airway remolding and inflammatory response mediated by bronchial epithelial cells. Further investigation demonstrated an underlying molecular mechanism for the therapeutic effects of curcumin may rely on the inhibition of the degradation of IκBα and COX-2 expression in curcumin+LC-treated COPD mice and LPS-stimulated BEAS-2B cells. Overall, curcumin alleviates the airway inflammation and airway remolding, which is closely related to inhibit the BEAS-2B cells proliferation and suppress the activation of NF-κB and COX-2 expression. These findings indicate that curcumin may be a potential agent for the therapy of COPD.

Topics: Airway Remodeling; Animals; Bronchi; Cell Line; Curcumin; Cyclooxygenase 2; Epithelial Cells; Humans; Inflammation; Mice; NF-kappa B; NF-KappaB Inhibitor alpha; Pulmonary Disease, Chronic Obstructive; Smoke; Tobacco Products

Psoriasis is a chronic autoimmune disease mediated by dysregulated immune responses in dendritic cells (DC) and T cells. The stress-response enzyme heme oxygenase-1 (HO-1) has been described as protective in animal models of psoriasis, however, implementation of HO-1-based therapies is hindered by the lack of clinically-suitable HO-1 inducers. The plant-derived polyphenols, carnosol and curcumin, have been identified as candidate HO-1 inducers however there has been little investigation into their effects on human immune cells. We demonstrate that treatment of human DC with these polyphenols limits DC maturation, reduces pro-inflammatory cytokine production, and prevents induction of allospecific T cell responses, in a manner partially dependent on carbon monoxide (CO). We also characterised their effects in ex-vivo psoriasis PBMC and report that curcumin, but not carnosol, strongly reduces T cell proliferation and cytokine poly-functionality, with reduced expression of psoriatic cytokines IFNγ, IL-17, GM-CSF and IL-22. This study therefore supports reports highlighting the therapeutic potential of curcumin in psoriasis by providing insight into its immunological effects on healthy human DC and psoriasis PBMC. We also demonstrate, for the first time, the anti-inflammatory effects of carnosol in human immune cells.

Topics: Abietanes; Anti-Inflammatory Agents, Non-Steroidal; Carbon Monoxide; Cell Differentiation; Cell Proliferation; Curcumin; Dendritic Cells; Enzyme Activation; Gene Expression Regulation, Enzymologic; Heme Oxygenase-1; Humans; Inflammation; Leukocytes, Mononuclear; Lymphocyte Activation; Psoriasis; T-Lymphocytes

Curcumin has recently been shown to be a potential treatment for slowing or ameloriating cognitive decline during aging in our nonhuman primate model of normal aging. In these same monkeys, we studied for the first time the neurological impacts of long-term curcumin treatments using longitudinal magnetic resonance imaging (MRI). Sixteen rhesus monkeys received curcumin or a vehicle control for 14-18 months. We applied a combination of structural and diffusion MRI to determine whether the curcumin resulted in structural or functional changes in focal regions of the brain. The longitudinal imaging revealed decreased microscale diffusivity (mD) measurements mainly in the hippocampus and basal forebrain structures of curcumin treated animals. Changes in generalized fractional anisotropy (GFA) and grey matter density (GMd) measurements indicated an increased grey matter density in cortical ROIs with improved white matter integrity in limbic, cerebellar, and brain stem regions. These findings suggest that noticeable changes in the neuronal environment could be induced from long-term curcumin treatments. Results may provide a neurological basis on the recent findings demonstrating improved spatial working memory and motor function in nonhuman primates.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Brain; Curcumin; Female; Image Processing, Computer-Assisted; Inflammation; Longitudinal Studies; Macaca mulatta; Magnetic Resonance Imaging; Male; Memory, Short-Term; Motor Activity; Nootropic Agents; Spatial Memory; Time Factors

Excess mucus production is an important pathophysiological feature of chronic inflammatory airway diseases. Effective therapies are currently lacking. The aim of the study was to evaluate the effects of curcumin (CUR) on lipopolysaccharide (LPS)-induced mucus secretion and inflammation, and explored the underlying mechanism in vivo and in vitro.. For the in vitro study, human bronchial epithelial (NCI-H292) cells were pretreated with CUR or vehicle for 30 min, and then exposed to LPS for 24 h. Next, nuclear factor erythroid 2-related factor 2 (Nrf2) was knocked down with Nrf2 small interfering RNA (siRNA) to confirm the specific role of Nrf2 in mucin regulation of CUR in NCI-H292 cells. In vivo, C57BL/6 mice were randomly assigned to three groups (n = 7 for each group): control group, LPS group, and LPS + CUR group. Mice in LPS and LPS + CUR group were injected with saline or CUR (50 mg/kg) intraperitoneally 2 h before intratracheal instillation with LPS (100 μg/ml) for 7 days. Cell lysate and lung tissue were obtained to measured Mucin 5AC (MUC5AC) and Nrf2 mRNA and protein expression by a real-time polymerase chain reaction and Western blotting. Bronchoalveolar lavage fluid (BALF) was collected to enumerate total cells and neutrophils. Histopathological changes of the lung were observed. Data were analyzed by one-way analysis of variance. Student's t-test was used when two groups were compared.. CUR significantly decreased the expression of MUC5AC mRNA and protein in NCI-H292 cells exposed to LPS. This effect was dose dependent (2.424 ± 0.318 vs. 7.169 ± 1.785, t = 4.534, and 1.060 ± 0.197 vs. 2.340 ± 0.209, t = 7.716; both P < 0.05, respectively) and accompanied by increased mRNA and protein expression of Nrf2 (1.952 ± 0.340 vs. 1.142 ± 0.176, t = -3.661, and 2.010 ± 0.209 vs. 1.089 ± 0.132, t = -6.453; both P < 0.05, respectively). Furthermore, knockdown of Nrf2 with siRNA increased MUC5AC mRNA expression by 47.7%, compared with levels observed in the siRNA-negative group (6.845 ± 1.478 vs. 3.391 ± 0.517, t = -3.821, P < 0.05). Knockdown of Nrf2 with siRNA also markedly increased MUC5AC protein expression in NCI-H292 cells. CUR also significantly decreased LPS-induced mRNA and protein expression of MUC5AC in mouse lung (1.672 ± 0.721 vs. 5.961 ± 2.452, t = 2.906, and 0.480 ± 0.191 vs. 2.290 ± 0.834, t = 3.665, respectively; both P < 0.05). Alcian blue/periodic acid-Schiff staining also showed that CUR suppressed mucin production. Compared with the LPS group, the numbers of inflammatory cells (247 ± 30 vs. 334 ± 24, t = 3.901, P < 0.05) and neutrophils (185 ± 22 vs. 246 ± 20, t = 3.566, P < 0.05) in BALF decreased in the LPS + CUR group, as well as reduced inflammatory cell infiltration in lung tissue.. CUR inhibits LPS-induced airway mucus hypersecretion and inflammation through activation of Nrf2 possibly.

Topics: Animals; Curcumin; Humans; Inflammation; Lipopolysaccharides; Mice; Mice, Inbred C57BL; Mucin 5AC; Random Allocation; Respiratory System

Curcumin exerts multiple functions including antioxidant and anti-inflammation, and has been shown protective potential on neurological disorders. Maternal or intrauterine infection/inflammation is one of the major factors underlying perinatal brain damage. This study aimed to determine whether maternal administration of curcumin has attenuation on neuroinflammation in fetal brain caused by lipopolysaccharide (LPS) administration.. LPS was used to establish mouse fetal brain injury model, and we investigated the effects of curcumin (40 mg/kg) on the fetal mouse brain by evaluating the morphological change of the neuronal cells and the expression of different pro-inflammatory cytokines and chemokines at protein and mRNA levels in the fetal brains, the maternal serum and amniotic fluid.. Our results demonstrated that maternal administration of curcumin has attenuation on neuroinflammation in the fetal brain induced by LPS. Pretreatment of curcumin in the LPS-induced mice effectively reestablished the neuronal cell morphology, attenuated the expression of soluble intercellular adhesion molecule-1, sE-Selectin, macrophage chemoattractant protein-1 and cytokine-induced neutrophil chemoattractant-1 in the maternal serum, decreased the expression of cyclooxygenase-2, interleukin-1 beta and chemokine (C-C motif) ligand 2 in the brain, and suppressed interleukin-6 (IL-6) mRNA transcription in the amniotic fluid. In addition, curcumin suppressed the LPS-induced microglia activation.. Our study in animal models indicates that maternal administration of curcumin alleviates neuroinflammation in the fetal brain caused by LPS. Long-term consumption of curcumin might improve the neurological outcomes of premature neonates delivered from dams suffering from infection/ inflammation.

Topics: Amniotic Fluid; Animals; Anti-Inflammatory Agents, Non-Steroidal; Brain; Cells, Cultured; Curcumin; Cytokines; Disease Models, Animal; Female; Inflammation; Lipopolysaccharides; Mice, Inbred BALB C; Microglia; Neurons; Neuroprotective Agents; Pregnancy; Pregnancy Complications, Infectious; RNA, Messenger

Estrogen receptor α (ERα) is a ligand-activated transcriptional activator that is also involved vascular inflammation and atherosclerosis. Whether different ligands may affect this activity has not been explored. We screened a panel of phytoestrogens for their role in ERα binding and transcriptional transcription, and correlated the findings to anti-inflammatory activities in vascular endothelial cells stably expressing either a wild-type or mutant form of ERα deficient in its membrane association. Taxifolin and silymarin were "high binders" for ERα ligand binding; quercetin and curcumin were "high activators" for ERα transactivation. Using these phytoestrogens as functional probes, we found, in endothelial cells expressing wild-type ERα, the ERα high activator, but not the ERα high binder, promoted ERα nuclear translocation, estrogen response element (ERE) reporter activity, and the downstream gene expression. In endothelial cells expressing membrane association-deficient mutant ERα, the ERα nuclear translocation was significantly enhanced by taxifolin and silymarin, which still failed to activate ERα. Inflammation response was examined using the systemic or vascular inflammation inducers lipopolysaccharide or oxidized low-density lipoprotein. In both cases, only the ERα high activator inhibited nuclear translocation of nuclear factor κB, JNK, and p38, and the production of inflammatory cytokines IL-1β and TNFα. We confirm a threshold nuclear accumulation of ERα is necessary for its transactivation. The anti-inflammatory activity of phytoestrogens is highly dependent on ERα transactivation, less so on the ligand binding, and independent of its membrane association. A pre-examination of phytoestrogens for their mode of ERα interaction could facilitate their development as better targeted receptor modifiers.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Antioxidants; Atherosclerosis; Cell Line; Curcumin; Endothelial Cells; Estrogen Receptor alpha; Humans; Inflammation; Interleukin-1beta; Ligands; Lipopolysaccharides; Lipoproteins, LDL; MAP Kinase Kinase 4; Molecular Docking Simulation; Mutation; NF-kappa B; p38 Mitogen-Activated Protein Kinases; Phytoestrogens; Protein Transport; Quercetin; Response Elements; Signal Transduction; Silymarin; Tumor Necrosis Factor-alpha

Previous studies in various rodent epilepsy models have suggested that mammalian target of rapamycin (mTOR) inhibition with rapamycin has anti-epileptogenic potential. Since treatment with rapamycin produces unwanted side effects, there is growing interest to study alternatives to rapamycin as anti-epileptogenic drugs. Therefore, we investigated curcumin, the main component of the natural spice turmeric. Curcumin is known to have anti-inflammatory and anti-oxidant effects and has been reported to inhibit the mTOR pathway. These properties make it a potential anti-epileptogenic compound and an alternative for rapamycin.. To study the anti-epileptogenic potential of curcumin compared to rapamycin, we first studied the effects of both compounds on mTOR activation, inflammation, and oxidative stress in vitro, using cell cultures of human fetal astrocytes and the neuronal cell line SH-SY5Y. Next, we investigated the effects of rapamycin and intracerebrally applied curcumin on status epilepticus (SE)-induced inflammation and oxidative stress in hippocampal tissue, during early stages of epileptogenesis in the post-electrical SE rat model for temporal lobe epilepsy (TLE).. Rapamycin, but not curcumin, suppressed mTOR activation in cultured astrocytes. Instead, curcumin suppressed the mitogen-activated protein kinase (MAPK) pathway. Quantitative real-time PCR analysis revealed that curcumin, but not rapamycin, reduced the levels of inflammatory markers IL-6 and COX-2 in cultured astrocytes that were challenged with IL-1β. In SH-SY5Y cells, curcumin reduced reactive oxygen species (ROS) levels, suggesting anti-oxidant effects. In the post-SE rat model, however, treatment with rapamycin or curcumin did not suppress the expression of inflammatory and oxidative stress markers 1 week after SE.. These results indicate anti-inflammatory and anti-oxidant properties of curcumin, but not rapamycin, in vitro. Intracerebrally applied curcumin modified the MAPK pathway in vivo at 1 week after SE but failed to produce anti-inflammatory or anti-oxidant effects. Future studies should be directed to increasing the bioavailability of curcumin (or related compounds) in the brain to assess its anti-epileptogenic potential in vivo.

Topics: Animals; Anti-Inflammatory Agents; Astrocytes; Brain; Cells, Cultured; Curcumin; Cytokines; Disease Models, Animal; Fetus; Gene Expression Regulation; Humans; Inflammation; Male; Neuroblastoma; Neurons; Oxidative Stress; Rats; Rats, Sprague-Dawley; Signal Transduction; Sirolimus; Status Epilepticus

Rats with a normal birth weight (NBW) or intra-uterine growth retardation (IUGR) were fed basic diets (NBW and IUGR groups) or basic diets supplemented with curcumin (NC and IC groups) from 6 to 12 weeks. The body weight of IUGR rats was lower (P<0·05) than that of the controls. Rats with IUGR showed higher (P<0·05) concentrations of TNF-α, IL-1β and IL-6; higher (P<0·05) activities of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in their serum; and increased (P<0·05) concentrations of malondialdehyde (MDA), protein carbonyl (PC) and 8-hydroxy-2'-deoxyguanosine (8-OHDG) in the liver compared with the NBW rats. The livers of IUGR rats exhibited a lower (P<0·05) superoxide dismutase activity and decreased (P<0·05) metabolic efficiency of the hepatic glutathione redox cycle compared with those of the NBW rats. In response to dietary curcumin supplementation, concentrations of inflammatory cytokines and activities of AST and ALT in the serum and MDA, PC and 8-OHDG in the liver were lower (P<0·05), and the hepatic glutathione redox cycle in the liver was improved (P<0·05) in the IC group than in the IUGR group. These results were associated with lower (P<0·05) phosphorylated levels of the NF-κB pathway and Janus kinase 2 (JAK2) and higher (P<0·05) mRNA expression of genes involved in the nuclear factor, erythroid 2-like 2 (Nfe2l2)/antioxidant response element (ARE) pathway in the liver of the IC rats than that of the IUGR rats. Maternal undernutrition decreased birth weight and led to inflammation, oxidative damage and injury in rats. Curcumin appeared to be beneficial in preventing IUGR-induced inflammation, oxidative damage and injury by activating the expression of the NF-κB, JAK/STAT and Nfe2l2/ARE pathways in the liver.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Alanine Transaminase; Animals; Animals, Newborn; Aspartate Aminotransferases; ATP-Binding Cassette Transporters; Birth Weight; Caenorhabditis elegans Proteins; Curcumin; Cytokines; Deoxyguanosine; Dietary Supplements; Disease Models, Animal; Female; Fetal Growth Retardation; Gene Expression; Inflammation; Liver; Liver Diseases; Oxidation-Reduction; Oxidative Stress; Pregnancy; Rats

Epilepsy is a chronic neurological disorder affecting an estimated 50 million people worldwide. Emerging evidences have accumulated over the past decades supporting the role of inflammation in the pathogenesis of epilepsy. Curcumin is a nature-derived active molecule demonstrating anti-inflammation efficacy. However, its effects on epilepsy and corresponding mechanisms remain elusive.. To investigate the effects of curcumin on epilepsy and its underlying mechanism.. Forty Sprague Dawley rats were divided into four groups: (1) control group; (2) Kainic Acid (KA)-induced epilepsy group; (3) curcumin group; and (4) curcumin pretreatment before KA stimulation group. Morris water maze was utilized to assess the effect of curcumin on KA-induced epilepsy. The hippocampi were obtained from rats and subjected to western blot. Immunohistochemistry was conducted to investigate the underlying mechanisms.. Rats received curcumin demonstrated improvement of recognition deficiency and epilepsy syndromes induced by KA. Western blot showed that KA stimulation increased the expression of IL-1β and NLRP3, which were reduced by curcumin treatment. Further investigations revealed that curcumin inhibited the activation of NLPR3/inflammasome in epilepsy and reduced neuronal loss in hippocampus.. Curcumin inhibits KA-induced epileptic syndromes via suppression of NLRP3 inflammasome activation; therefore, offers a potential therapy for epilepsy.

Topics: Animals; Anti-Inflammatory Agents; Cognition Disorders; Curcumin; Disease Models, Animal; Epilepsy; Excitatory Amino Acid Agonists; Female; Hippocampus; Inflammation; Interleukin-1beta; Kainic Acid; Male; Maze Learning; Neurons; NLR Family, Pyrin Domain-Containing 3 Protein; Rats; Rats, Sprague-Dawley

Curcumin a component of turmeric, which is derived from Curcuma longa is used as a colouring agent and as a dietary spice for centuries. Extensive studies have been done on the anti-inflammatory activity of curcumin along with its molecular mechanism involving different signalling pathways. However, the physicochemical and biological properties such as poor solubility and rapid metabolism of curcumin have led to low bioavailability and hence limits its application. Current therapies for asthma such as bronchodilators and inhaled corticosteroids (ICS) are aimed at controlling disease symptoms and prevent asthma exacerbation. However, this approach requires lifetime therapy and is associated with a constellation of side effects. This creates a clear unmet medical need and there is an urgent demand for new and more-effective treatments. The present study is aimed to formulate liposomes containing curcumin and evaluate for its anti-inflammatory effects on lipopolysaccharide (LPS)-induced inflammation on BCi-NS1.1 cell line. Curcumin and salbutamol liposomes were formulated using lipid hydration method. The prepared liposomes were characterized in terms of particle size, zeta potential, encapsulation efficiency and in-vitro release profile. The liposomes were tested on BCI-NS1.1 cell line to evaluate its anti-inflammatory properties. The various pro-inflammatory markers studied were Interleukin-6 (IL-6), Interleukin-8 (IL-8), Interleukin-1β (IL-1β) and Tumour Necrosis Factor-a (TNF-a). Additionally, molecular mechanics simulations were used to elucidate the positioning, energy minimization, and aqueous dispersion of the liposomal architecture involving lecithin and curcumin. The prepared curcumin formulation showed an average size and zeta potential of 271.3 ± 3.06 nm and -61.0 mV, respectively. The drug encapsulation efficiency of liposomal curcumin is 81.1%. Both curcumin-loaded liposomes formulation (1 μg/mL, 5 μg/mL) resulted in significant (p < 0.05) reduction in the level of pro-inflammatory marker expression such as IL-6, IL-8, IL-1β and TNF-a compared to positive control group. Liposomal curcumin with the dose of 1 μg/mL reduced the inflammatory markers more effectively compared to that of 5 μg/mL. Liposomal curcumin could be a promising intervention for asthma therapy showing their efficacy in suppressing the important pro-inflammatory markers involved in the pathogenesis of asthma.

Topics: Asthma; Biomarkers; Cell Line; Computer Simulation; Curcumin; Drug Liberation; Humans; Inflammation; Liposomes; Models, Molecular; Particle Size; Spectroscopy, Fourier Transform Infrared; Static Electricity

Colistin is an effective antibiotic against multidrug-resistant (MDR) gram-negative bacterial infections; however, nephrotoxic and neurotoxic effects are fundamental dose-limiting factors for this treatment. This study was conducted to assess the potential protective effects of curcumin, a phenolic constituent of turmeric, against colistin-induced nephrotoxicity and neurotoxicity, and the possible mechanisms underlying any effect. Twenty-four adult male albino rats were randomly classified into 4 equal groups; the control group (orally received saline solution), the curcumin-treated group (orally administered 200 mg curcumin/kg/day), the colistin-treated group (IP administered 300,000 IU colistin/kg/day) and the concurrent group (orally received 200 mg curcumin/kg/day concurrently with colistin injection); all rats were treated for 6 successive days. Colistin administration significantly increased serum creatinine, urea and uric acid levels as well as brain gamma butyric acid (GABA) concentrations. In renal and brain tissues, colistin significantly increased malondialdehyde (MDA), nitric oxide (NO), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and caspase-3 expression levels. In addition, colistin significantly decreased catalase (CAT), glutathione (GSH), and B-cell lymphoma 2 (Bcl-2) expressions. Curcumin administration in colistin-treated rats partially restored each of these altered biochemical, antioxidant, inflammatory and apoptotic markers. Histopathological changes in renal and brain tissues were also alleviated by curcumin co-treatment. Our study reveals a critical role of oxidative damage, inflammation and apoptosis in colistin-induced nephrotoxicity and neurotoxicity and showed that they were markedly ameliorated by curcumin co-administration. Therefore, curcumin could represent a promising agent for prevention of colistin-induced nephrotoxicity and neurotoxicity.

Topics: Animals; Apoptosis; Brain; Caspase 3; Catalase; Colistin; Curcumin; Glutathione; Inflammation; Interleukin-6; Kidney; Male; Malondialdehyde; Nitric Oxide; Oxidative Stress; Proto-Oncogene Proteins c-bcl-2; Rats; Tumor Necrosis Factor-alpha

Microglial inflammation plays an essential role in the pathogenesis of HIV-associated neurocognitive disorders. A previous study indicated that curcumin relieved microglial inflammatory responses. However, the mechanism of this process remained unclear. Autophagy is a lysosome-mediated cell content-dependent degradation pathway, and uncontrolled autophagy leads to enhanced inflammation. The role of autophagy in curcumin-attenuating BV2 cell inflammation caused by gp120 was investigated with or without pretreatment with the autophagy inhibitor 3-MA and blockers of NF-κB, IKK, AKT, and PI3K, and we then detected the production of the inflammatory mediators monocyte chemoattractant protein-1 (MCP-1) and IL17 using ELISA, and autophagy markers ATG5 and LC3 II by Western Blot. The autophagic flux was observed by transuding mRFP-GFP-LC3 adenovirus. The effect of the blockers on gp120-induced BV2 cells was examined by the expression of p-AKT, p-IKK, NF-κB, and p65 in the nuclei and LC3 II and ATG5. gp120 promoted the expression of MCP-1 and IL-17, enhanced autophagic flux, and up-regulated the expression of LC3 II and ATG5, while the autophagy inhibitor 3-MA down-regulated the phenomena above. Curcumin has similar effects with 3-MA, in which curcumin inhibited NF-κB by preventing the translocation of NF-κB p65. Curcumin also inhibited the phosphorylation of p-PI3K, p-AKT, and p-IKK, which leads to down-regulation of NF-κB. Curcumin reduced autophagy via PI3K/AKT/IKK/NF-κB, thereby reducing BV2 cellular inflammation induced by gp120.

Topics: Animals; Autophagosomes; Autophagy; Chemokine CCL2; Curcumin; HIV Envelope Protein gp120; I-kappa B Proteins; Inflammation; Interleukin-17; Mice; Microglia; NF-kappa B; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Signal Transduction

Topics: Animals; Curcumin; Drug Delivery Systems; Gold; Humans; Inflammation; Metal Nanoparticles; Mice; Mice, Inbred BALB C; Nanotechnology; Reactive Oxygen Species; Respiration Disorders; Solubility

Excess fructose consumption causes high prevalence of metabolic syndrome and inflammatory liver diseases. The aim of the current study was to investigate the therapeutic effects and underlying molecular mechanisms of curcumin and allopurinol in high fructose-induced hepatic inflammation. Male Sprague-Dawley rats were supplied with standard rat chow and drinking water containing 10% (w/v) fructose for consecutive 12 weeks. Curcumin (15, 30 and 60 mg/kg) and allopurinol (5 mg/kg) were administered to rats via oral gavage daily from Week 7 to 12. For in vitro experiments, curcumin (2.5 μM) and allopurinol (100 μM) were treated to 5 mM fructose-exposed Buffalo rat liver cell line (BRL-3 A) and human hepatoblastoma cell line (HepG2), respectively. The data from these animal and hepatocyte models showed that curcumin and allopurinol ameliorated fructose-induced metabolic symptom, especially hepatic inflammation in rats. Interestingly, down-regulation of microRNA-200a (miR-200a) was screened out in livers of fructose-fed rats and then validated in fructose-exposed BRL-3 A and HepG2 cells. Fructose-induced miR-200a low-expression was identified as a negative mediator of thioredoxin interacting protein (TXNIP) by direct targeting of 3'UTR-rTXNIP, subsequently activating the NOD-like receptor pyrin domain containing 3 (NLRP3) inflammasome in BRL-3 A cells. Curcumin, as well as allopurinol, notably up-regulated miR-200a expression, accordingly, down-regulated TXNIP and inhibited NLRP3 inflammasome activation in fructose-fed rat livers and fructose-exposed BRL-3 A and HepG2 cells. Taken together, this study firstly identified miR-200a as a biomarker of fructose-induced hepatic inflammation, and revealed the hepatoprotection of curcumin and allopurinol via up-regulating miR-200a-mediated TXNIP/NLRP3 inflammasome pathway.

Topics: Allopurinol; Animals; Carrier Proteins; Cell Cycle Proteins; Cell Line; Curcumin; Fructose; Humans; Inflammation; Liver; Male; MicroRNAs; NLR Family, Pyrin Domain-Containing 3 Protein; Protective Agents; Rats, Sprague-Dawley

Inhibiting the onset of arteriosclerotic disease, which has been increasing due to the westernized diet and aging, is a significant social challenge. Curcumin, a type of polyphenol, has anti-oxidative effects and anti-inflammatory action and is expected to treat and to have prophylactic effects on different diseases. In this study, we examined the effects of long-term administration of curcumin on vascular aging and chronic inflammation-the causes of arteriosclerotic disease. Eight-week-old C57BL/6J mice were fed with high fat diet (HFD) or 0.1% curcumin-mixed HFD (HFD + Cu) until 80 weeks old (

Topics: Aging; Animals; Anti-Inflammatory Agents, Non-Steroidal; Antioxidants; Aorta; Arteriosclerosis; Curcumin; Diet, High-Fat; Inflammation; Male; Mice; Mice, Inbred C57BL; Oxidative Stress; Sirtuin 1

Diabetic cardiomyopathy is an independent cardiac injury that can develop in diabetic individuals. Our previous study showed that C66, a curcumin analogue, protects against diabetes-induced cardiac damage. The present study sought to reveal the underlying mechanisms of C66-mediated cardioprotection.. Neither C66 treatment nor JNK2 knockout affected body weight or plasma glucose levels. Cardiac inflammation, fibrosis, oxidative stress, and apoptosis were increased in WT diabetic compared to WT control mice, all of which were attenuated by C66 treatment. However, these pathological and molecular changes induced by diabetes were eliminated in JNK2. Our results indicate that C66 ameliorates diabetic cardiomyopathy by inhibiting JNK2 relative pathways.

Topics: Animals; Apoptosis; Curcumin; Diabetes Mellitus, Experimental; Diabetic Cardiomyopathies; Diabetic Nephropathies; Fibrosis; Humans; Inflammation; Mice; Mice, Inbred NOD; Mitogen-Activated Protein Kinase 9; Oxidative Stress; Phosphorylation

Curcumin has several therapeutic properties such as anti-inflammatory effect. Heme oxygenase-1 (HO-1) has been showed to have cytoprotective effects in some pathological conditions. However, the role of HO-1 in anti-inflammatory effect of curcumin is unknown. In this study, we investigate whether the anti-inflammatory effect of curcumin in vascular may be involved in the activation of HO-1. New Zealand white rabbits were fed regular control diet or control diet added with 0.3% curcumin (wt/wt) for four weeks. Acute vascular inflammation of rabbits was induced by putting a collar on the left common carotid artery for 24 hours. HO-1 inhibitor and siRNA were used to investigate the role of HO-1 in the anti-inflammatory effect of curcumin in collared vascular. We also explored the mechanism of curcumin-induced activation of HO-1 in vitro. The serum bilirubin and vascular, liver, and spleen HO-1 mRNA levels were significantly increased in curcumin-treated rabbits. The vascular inflammation was significantly decreased in the curcumin-treated animals compared with the control. Treatment of the rabbits with an inhibitor of HO or HO-1 siRNA to knock down the carotid artery HO-1 abolished the ability of curcumin to inhibit vascular inflammation. Treatment of cultured human artery endothelial cells with curcumin induced the HO-1 expression through the activation of nuclear factor-E2-related factor 2 (Nrf2) and an antioxidant responsive element via the p38 MAPK signalling pathway. In conclusion, curcumin inhibits vascular inflammation in vivo and in vitro through the activation of HO-1.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Carotid Artery, Common; Curcumin; Endothelium, Vascular; Enzyme Activation; Heme Oxygenase-1; Humans; Inflammation; Rabbits

Ozone is a harmful tropospheric pollutant, causing the formation of reactive oxygen and nitrogen species that lead to oxidative damage in living beings. NF-

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Curcumin; Cytokines; Hippocampus; Inflammation; Inflammation Mediators; Male; Neuroprotection; NF-kappa B; Oxidative Stress; Ozone; Rats; Rats, Wistar

Topics: Animals; Anti-Inflammatory Agents; Cell Line; Cell Survival; Curcuma; Fibroblasts; Gene Expression; Humans; Inflammation; Lipopolysaccharides; MAP Kinase Signaling System; Mice; Molecular Structure; Osteoclasts; Osteogenesis; Phenols; Plant Extracts; RANK Ligand; RAW 264.7 Cells

Curcuma zedoaroides, a Zingiberaceae species, has been used for snake bite antidote and wound care in Thailand. Seven compounds were isolated from the bioactive chloroform extract consisted of one new guaiane sesquiterpene lactone, 5-epiphaeocaulisin A (4) and one new diarylheptanoid, 1,2,3,5-tetrahydroxy-1-(4-hydroxy-3-methoxyphenyl)-7-(4-hydroxyphenyl) heptane (7), together with five known guaiane-type sesquiterpene lactones including gweicurculactone (1), zedoalactone B (2), phaeocaulisin C (3), zedoalactone H (5), and zedoalactone E (6). The antiinflammation was investigated on NO and TNF-α production using RAW264.7 cells. In addition, the expressions of genes involved in inflammation including iNOS, COX-2, and TNF-α were assessed. The results found that Compounds 1-7 presented their antiinflammation against NO production. The most potential effects were demonstrated on Compounds 1 and 7 with IC

Topics: Animals; Anti-Inflammatory Agents; Azulenes; Curcuma; Cyclooxygenase 2; Inflammation; Lactones; Mice; Molecular Structure; Nitric Oxide; Nitric Oxide Synthase Type II; Plant Extracts; RAW 264.7 Cells; Rhizome; Sesquiterpenes; Sesquiterpenes, Guaiane; Thailand; Tumor Necrosis Factor-alpha

Periodontitis, which is a severe inflammatory disease caused by endotoxins secreted from oral pathogens, destructs gingival tissue and alveolar bone.

Topics: Alveolar Bone Loss; Animals; Anti-Inflammatory Agents; Bone Remodeling; Curcuma; Disease Models, Animal; Gene Expression; Gingiva; Inflammation; Lipopolysaccharides; Male; Osteoblasts; Osteogenesis; Periodontitis; Phenols; Plant Extracts; Rats; Rats, Sprague-Dawley

Curcumin is an Indian spice with a wide spectrum of biological and pharmacological activities but poor aqueous solubility, rapid degradation, and low bioavailability that affect medical benefits. To overcome these limits in ophthalmic application, curcumin was entrapped in a polycationic calix[4]arene-based nanoaggregate by a simple and reproducible method. The calix[4]arene-curcumin supramolecular assembly (Calix-Cur) appeared as a clear colloidal solution consisting in micellar nanoaggregates with size, polydispersity index, surface potential, and drug loading percentage meeting the requirements for an ocular drug delivery system. The encapsulation in the calix[4]arene nanoassembly markedly enhanced the solubility, reduced the degradation, and improved the anti-inflammatory effects of curcumin compared to free curcumin in both in vitro and in vivo experiments. Calix-Cur did not compromise the viability of J774A.1 macrophages and suppressed pro-inflammatory marker expression in J774A.1 macrophages subjected to LPS-induced oxidative stress. Histological and immunohistochemical analyses showed that Calix-Cur reduced signs of inflammation in a rat model of LPS-induced uveitis when topically administrated in the eyes. Overall, the results supported the calix[4]arene nanoassembly as a promising nanocarrier for delivering curcumin to anterior ocular tissues.

Topics: Animals; Calixarenes; Cell Line; Curcumin; Drug Carriers; Inflammation; Macrophages; Ophthalmic Solutions; Phenols; Uveitis

At present, it has become evident that inflammation plays a critical role in tumor growth; meanwhile, chemotherapeutic agents using nanocarriers have been suggested as a promising strategy in cancer treatment. In this study, novel redox-responsive micelles were prepared from monomethoxy-poly(ethylene glycol)-chitosan-S-S-hexadecyl (C

Topics: Animals; Anti-Inflammatory Agents; Antineoplastic Agents; Apoptosis; Cell Survival; Chitosan; Curcumin; Drug Carriers; Drug Liberation; Endocytosis; Fluorescence; Humans; Inflammation; MCF-7 Cells; Mice; Mice, Inbred C57BL; Mice, Nude; Micelles; NIH 3T3 Cells; Oxidation-Reduction; Polyethylene Glycols; Tissue Distribution; Tumor Necrosis Factor-alpha

Various studies have indicated a lower incidence and prevalence of neurological conditions in people consuming curcumin. The ability of curcumin to target multiple cascades, simultaneously, could be held responsible for its neuroprotective effects. The present study was designed to investigate the potential of curcumin in minimizing microglia-mediated damage in lipopolysaccharide (LPS) induced model of PD. Altered microglial functions and increased inflammatory profile of the CNS have severe behavioral consequences. In the current investigation, a single injection of LPS (5 ug/5 µl PBS) was injected into the substantia nigra (SN) of rats, and curcumin [40 mg/kg b.wt (i.p.)] was administered daily for a period of 21 days. LPS triggered an inflammatory response characterized by glial activation [Iba-1 and glial fibrillary acidic protein (GFAP)] and pro-inflammatory cytokine production (TNF-α and IL-1β) leading to extensive dopaminergic loss and behavioral abnormality in rats. The behavioral observations, biochemical markers, quantification of dopamine and its metabolites (DOPAC and HVA) using HPLC followed by IHC of tyrosine hydroxylase (TH) were evaluated after 21 days of LPS injection. Curcumin supplementation prevented dopaminergic degeneration in LPS-treated animals by normalizing the altered levels of biomarkers. Also, a significant improvement in TH levels as well as behavioral parameters (actophotometer, rotarod, beam walking and grid walking tests) were seen in LPS injected rats. Curcumin shielded the dopaminergic neurons against LPS-induced inflammatory response, which was associated with suppression of glial activation (microglia and astrocytes) and transcription factor NF-κB as depicted from RT-PCR and EMSA assay. Curcumin also suppressed microglial NADPH oxidase activation as observed from NADPH oxidase activity. The results suggested that one of the important mechanisms by which curcumin mediates its protective effects in the LPS-induced PD model is by inhibiting glial activation. Therefore, curcumin could be a potential therapeutic agent for inflammation-driven neurodegenerative disorders like PD, and its neuroprotective role should be explored further.

Topics: Animals; Biomarkers; Curcumin; Cytokines; Dopaminergic Neurons; Inflammation; Inflammation Mediators; Lipopolysaccharides; Male; Microglia; Motor Activity; NADPH Oxidases; Neuroglia; Neuroprotective Agents; NF-kappa B; Rats; Rats, Sprague-Dawley; Substantia Nigra; Tumor Necrosis Factor-alpha

Approaches to prevent selective and progressive loss of insulin-producing beta cells in Type 1 diabetes mellitus (T1DM) will help to manage this prevalent and devastating disease. Curcumin (CUR), a natural anti-inflammatory substance, suppresses diabetes-associated inflammation and cell death. However, very high doses need to be used because of poor oral bioavailability, making it difficult to translate the anti-inflammatory actions to clinical situations.. We have prepared biodegradable nanosystems encapsulating curcumin (nCUR), resulting in at least nine-fold improvement in oral bioavailability. Here, we tested the ability of nCUR to prevent streptozotocin (STZ)-induced inflammation and apoptosis in pancreatic islets and beta cells, in rats.. Non-fasted rats pretreated with 10 or 50 mg·kg. Together, these data indicate a potentially translatable dose of nCUR that is safe and efficacious in improving beta cell function, which could prevent T1DM.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Apoptosis; Curcumin; Diabetes Mellitus, Type 1; Dose-Response Relationship, Drug; Inflammation; Insulin-Secreting Cells; Male; Nanostructures; Rats; Rats, Sprague-Dawley; Streptozocin; Structure-Activity Relationship

Resveratrol and curcumin, as natural flavones products, have good therapeutic effect in acute and chronic inflammation; on the other hand, tetramethylpyrazine (TMP) has angiogenesis and vessel protection effect as well as anti-inflammatory function. In this paper, the anti-inflammatory effect of the tetramethylpyrazine, resveratrol and curcumin (TRC) combination in acute and chronic inflammation was reported in vivo.. The dose of the combined three natural products was optimized based on the acute paw swelling mouse model with a Uniform Design methodology. The therapeutic effect of TRC combination on chronic inflammation was investigated by using the collagen-induced arthritis (CIA) rat model based upon the following indexes: the volume of paw swelling, arthritis score, serum mediators and histological examination as well as immunohistochemical staining. The levels of alanine aminotransferase (ALT) and aspartate transaminase (AST) in serum were measured and the pathological sections of liver and kidney were analysed. LD. The results showed this formulation could provide a novel potent treatment for acute and chronic inflammation (RA) without side effect like gastric injury occurring in NSAIDs.

Topics: Alanine Transaminase; Animals; Anti-Inflammatory Agents; Arthritis, Experimental; Aspartate Aminotransferases; Cartilage; Curcumin; Cytokines; Drug Combinations; Edema; Female; Inflammation; Joints; Kidney; Liver; Male; Mice; NF-kappa B; Phytotherapy; Plant Extracts; Pyrazines; Rats, Sprague-Dawley; Resveratrol; Stilbenes

Current non-surgical treatments for lumbar radiculopathy [e.g. epidural steroids and Tumour necrosis factor-α (TNF-α) antagonists] are neither effective nor safe. As a non-toxic natural product, curcumin possesses an exceptional anti-inflammatory profile. We hypothesised that curcumin alleviates lumbar radiculopathy by attenuating neuroinflammation, oxidative stress and nociceptive factors. In a dorsal root ganglion (DRG) culture, curcumin effectively inhibited TNF-α-induced neuroinflammation, in a dose-dependent manner, as shown by mRNA and protein expression of IL-6 and COX-2. Such effects might be mediated via protein kinase B (AKT) and extracellular signal regulated kinase (ERK) pathways. Also, a similar effect in combating TNF-α-induced neuroinflammation was observed in isolated primary neurons. In addition, curcumin protected neurons from TNF-α-triggered excessive reactive oxygen species (ROS) production and cellular apoptosis and, accordingly, promoted mRNA expression of the anti-oxidative enzymes haem oxygenase-1, catalase and superoxide dismutase-2. Intriguingly, electronic von Frey test suggested that intraperitoneal injection of curcumin significantly abolished ipsilateral hyperalgesia secondary to disc herniation in mice, for up to 2 weeks post-surgery. Such in vivo pain alleviation could be attributed to the suppression, observed in DRG explant culture, of TNF-α-elicited neuropeptides, such as substance P and calcitonin gene-related peptide. Surprisingly, micro-computed tomography (μCT) data suggested that curcumin treatment could promote disc height recovery following disc herniation. Alcian blue/picrosirius red staining confirmed that systemic curcumin administration promoted regeneration of extracellular matrix proteins, visualised by presence of abundant newly-formed collagen and proteoglycan content in herniated disc. Our study provided pre-clinical evidence for expediting this natural, non-toxic pleiotropic agent to become a new and safe clinical treatment of radiculopathy.

Topics: Animals; Apoptosis; Cells, Cultured; Curcumin; Cytoprotection; Disease Models, Animal; Dose-Response Relationship, Drug; Female; Ganglia, Spinal; Hyperalgesia; Inflammation; Intervertebral Disc Displacement; Lumbar Vertebrae; Male; Mice, Inbred BALB C; Neurons; Neuropeptides; Nociception; Oxidative Stress; Radiculopathy; Reactive Oxygen Species; Staining and Labeling; Tumor Necrosis Factor-alpha

The purpose of this study is to determine if a preventive treatment with curcumin can protect intestinal epithelial cells from inflammatory damage induced by IFNγ. To achieve this goal we have used a human intestinal epithelial cell line (HT29) treated with IFNγ to undergo apoptotic changes that can reproduce the damage of intestinal epithelia exposed to inflammatory cytokines. In this model, we measured the effect of curcumin (curcuminoid from

Topics: Anti-Inflammatory Agents, Non-Steroidal; Apoptosis; Cell Survival; Curcuma; Curcumin; Cytokines; Epithelial Cells; HT29 Cells; Humans; Inflammation; Interferon-gamma; Interleukin-7; Intestinal Mucosa; NF-kappa B; Phosphorylation; Signal Transduction

The present study was carried out to understand the therapeutic effect of curcumin (CUR) against stroke in the experimental animal model. The study investigates the healing effect of CUR on mitochondrial dysfunction and inflammation.. Male albino, Wistar strain rats were used for the induction of middle cerebral artery occlusion (MCAO), and reperfusion. Enzyme-linked immunosorbent assay (ELISA) was used for the determination of interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α) in the brain region. Western blot analysis was used to determine the protein expression levels of Bax, Bcl-2, p53, and Sirt1.. The water level was determined in brain region by using standard method. Experimental results indicated that the use of CUR significantly reduced brain edema and water content. IL-6 and TNF-α were significantly reduced in the brain region following use of CUR. Mitochondrial membrane potential (MMP) also reduced significantly after CUR treatment. Protein expression of p53 and Bax were significantly reduced, whereas Bcl-2 and Sirt1 were increased following CUR treatment.. Taking all these data together, it is suggested that the use of CUR may be a potential therapeutic agent for the treatment of stroke.

Topics: Animals; Brain Edema; Curcumin; Disease Models, Animal; Enzyme-Linked Immunosorbent Assay; Gene Expression Regulation; Infarction, Middle Cerebral Artery; Inflammation; Interleukin-6; Male; Membrane Potential, Mitochondrial; Mitochondria; Rats; Rats, Wistar; Stroke; Tumor Necrosis Factor-alpha

This study assessed the effect of curcumin as a photosensitizer in antimicrobial photodynamic therapy (aPDT) for the treatment of induced periodontitis in rats. Periodontitis was induced via a ligature around the mandibular first molar on the left side of 96 rats. The ligature was removed 7 days later, and the animals were randomized into four groups: NT, no local treatment; CUR, irrigation with curcumin solution (40 μM); LED, irradiation with a light-emitting diode (LED, InGaN, 465-485 nm, 200 mW/cm

Topics: Animals; Curcumin; Inflammation; Male; Mandible; Molar; Osteoprotegerin; Periodontitis; Photochemotherapy; Proliferating Cell Nuclear Antigen; RANK Ligand; Rats, Wistar; Tartrate-Resistant Acid Phosphatase

A previous study demonstrated that particulate matter (≤2.5 µm in diameter; PM2.5) may promote atherosclerosis. However, the underlying mechanisms of PM2.5 in human microvascular endothelial cells (HMEC‑1) remain to be elucidated. It has been reported that inflammation and oxidative stress can be reduced by curcumin, and in the present study, the aim was to investigate the protective effects of curcumin on PM2.5‑induced oxidative stress and inflammatory response in HMEC‑1. HMEC‑1 were stimulated with curcumin and PM2.5. The HMEC‑1 viability and apoptosis were detected by MTT and annexin V‑fluorescein isothiocyanate/propidium iodide assays. The levels of oxidized low‑density lipoprotein (oxLDL), tumor necrosis factor (TNF)‑α and interleukin (IL)‑8 were detected by ELISA. The intracellular reactive oxygen species formation in HMEC‑1 was detected using flow cytometry and 2',7'‑dichlorofluorescin diacetate. Nuclear factor (NF)‑κB, caspase 3 activity and adhesion molecule expression were also investigated. The results suggested that curcumin reduced PM2.5 (300 µg/ml)‑induced cell apoptosis and intracellular caspase 3 activity in HMEC‑1. ELISA analysis demonstrated that curcumin reduced PM2.5‑induced oxLDL, TNF‑α and IL‑8 levels. Curcumin induced NF‑κB, cell adhesion molecule 1 and vascular cell adhesion protein 1 expression. Thus, curcumin treatment may reduce PM2.5‑induced oxidative stress and inflammation in HMEC‑1. In summary, it was indicated that the effects of PM2.5 are associated with oxLDL via the NF‑κB signaling pathway, thereby inducing PM2.5 mediated oxidative and inflammatory responses. The results also suggested that curcumin may be able to reduce the oxidative and inflammatory effects of PM2.5 in HMEC‑1.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Apoptosis; Cell Line; Curcumin; Endothelial Cells; Humans; Inflammation; Lipoproteins, LDL; Microvessels; NF-kappa B; Oxidative Stress; Particulate Matter; Protective Agents; Signal Transduction

Curcuma longa L. is a well-known medicinal plant that has been used for its anti-cancer, neuroprotective, and hepatoprotective effects. However, the neuroprotective effect of fermented C. longa (FCL) has not been reported. Therefore, in this study, the effectiveness of FCL for the regulation of memory dysfunction was investigated in two brain cell lines (rat glioma C6 and murine microglia BV2) and scopolamine-treated mice.. Pretreatment with FCL effectively prevented the cell death induced by oxidative stress in C6 cells. Moreover, FCL inhibited the production NO and PGE. FCL pretreatment could alleviate scopolamine-induced memory impairment in mice, as well as oxidative stress and inflammation in C6 and BV2 cells, respectively. Thus, FCL might be a useful material for preventing impairment of learning and memory.

Topics: Acetylcholinesterase; Amnesia; Animals; Anti-Inflammatory Agents; Antioxidants; Brain; Brain-Derived Neurotrophic Factor; Cell Line; Curcuma; Curcumin; Cyclic AMP Response Element-Binding Protein; Fermentation; Inflammation; Inflammation Mediators; Lipopolysaccharides; Male; Memory Disorders; Mice, Inbred ICR; Neuroprotective Agents; Oxidative Stress; Phytotherapy; Plant Extracts; Rats; Scopolamine

Moringa oleifera Lam. is a tropical plant, used for centuries as food and traditional medicine. The aim of this study was to develop, validate and biochemically characterize an isothiocyanate-enriched moringa seed extract (MSE), and to compare the anti-inflammatory effects of MSE-containing moringa isothiocyanate-1 (MIC-1) with a curcuminoid-enriched turmeric extract (CTE), and a material further enriched in its primary phytochemical, curcumin (curcumin-enriched material; CEM). MSE was prepared by incubating ground moringa seeds with water to allow myrosinase-catalyzed enzymatic formation of bioactive MIC-1, the predominant isothiocyanate in moringa seeds. Optimization of the extraction process yielded an extract of 38.9% MIC-1. Phytochemical analysis of MSE revealed the presence of acetylated isothiocyanates, phenolic glycosides unique to moringa, flavonoids, fats and fatty acids, proteins and carbohydrates. MSE showed a reduction in the carrageenan-induced rat paw edema (33% at 500 mg/kg MIC-1) comparable to aspirin (27% at 300 mg/kg), whereas CTE did not have any significant effect. In vitro, MIC-1 at 1 μM significantly reduced the production of nitric oxide (NO) and at 5 μM, the gene expression of LPS-inducible nitric oxide synthase (iNOS) and interleukins 1β and 6 (IL-1β and IL-6), whereas CEM did not show any significant activity at all concentrations tested. MIC-1 (10μM) was also more effective at upregulating the nuclear factor (erythroid-derived 2)-like 2 (Nrf2) target genes NAD(P)H:quinone oxidoreductase 1 (NQO1), glutathione S-transferase pi 1 (GSTP1), and heme oxygenase 1 (HO1) than the CEM. Thus, in contrast to CTE and CEM, MSE and its major isothiocyanate MIC-1 displayed strong anti-inflammatory and antioxidant properties in vivo and in vitro, making them promising botanical leads for the mitigation of inflammatory-mediated chronic disorders.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Antioxidants; Carrageenan; Cell Line; Curcuma; Curcumin; Disease Models, Animal; Drug Evaluation, Preclinical; Edema; Hindlimb; Inflammation; Isothiocyanates; Macrophages; Male; Moringa oleifera; Phytochemicals; Phytotherapy; Plant Extracts; Random Allocation; Rats, Sprague-Dawley; Seeds

Weight regain, adipose tissue growth, and insulin resistance can occur within days after the cessation of regular dieting and exercise. This phenomenon has been attributed, in part, to the actions of stress hormones as well as local and systemic inflammation. We investigated the effect of curcumin, a naturally occurring polyphenol known for its anti-inflammatory properties and inhibitory action on 11β-HSD1 activity, on preserving metabolic health and limiting adipose tissue growth following the cessation of daily exercise and caloric restriction (CR). Sprague-Dawley rats (6-7 wk old) underwent a "training" protocol of 24-h voluntary running wheel access and CR (15-20 g/day; ~50-65% of ad libitum intake) for 3 wk ("All Trained") or were sedentary and fed ad libitum ("Sed"). After 3 wk, All Trained were randomly divided into one group which was terminated immediately ("Trained"), and two detrained groups which had their wheels locked and were reintroduced to ad libitum feeding for 1 wk. The wheel locked groups received either a daily gavage of a placebo ("Detrained + Placebo") or curcumin (200 mg/kg) ("Detrained + Curcumin"). Cessation of daily CR and exercise caused an increase in body mass, as well as a 9- to 14-fold increase in epididymal, perirenal, and inguinal adipose tissue mass, all of which were attenuated by curcumin ( P < 0.05). Insulin area under the curve (AUC) during an oral glucose tolerance test, HOMA-IR, and C-reactive protein (CRP) were elevated 6-, 9-, and 2-fold, respectively, in the Detrained + Placebo group vs. the Trained group (all P < 0.05). Curcumin reduced insulin AUC, HOMA-IR, and CRP vs. the placebo group (all P < 0.05). Our results indicate that curcumin has a protective effect against weight regain and impaired metabolic control following a successful period of weight loss through diet and exercise, perhaps via inhibition of glucocorticoid action and inflammation. NEW & NOTEWORTHY Weight regain after dieting and exercise is a common phenomenon plaguing many individuals. The biological mechanisms underlying weight regain are incompletely understood and are likely multifactorial. In this paper, we examined the metabolic implications of curcumin, a compound known for its anti-inflammatory properties and inhibitory action on the enzyme 11β-HSD1, in a rodent model of adiposity rebound after the cessation of diet and exercise.

Topics: 11-beta-Hydroxysteroid Dehydrogenase Type 1; Adipose Tissue; Animals; Caloric Restriction; Corticosterone; Curcumin; Diet; Glucose Intolerance; Glucose Tolerance Test; Inflammation; Insulin Resistance; Male; Muscle, Skeletal; Obesity; Physical Conditioning, Animal; Random Allocation; Rats; Rats, Sprague-Dawley; Weight Gain

Traumatic spinal cord injury (SCI) is damage to the spinal cord that results in damaged spinal cord function. As a natural compound, curcumin has recently been shown to have anti-inflammatory and strong antioxidant activities. To investigate the effect of curcumin against acute spinal cord injury (SCI), we explored its induced effects in SCI mice. Transforming growth factor (TGF)-activated kinase 1 (TAK1) is a member of the MAPKKK family and plays an essential role in TNF, IL-1, and Toll-like receptor (TLR) signaling pathways.. One hundred adult female KM mice were randomly divided into 5 groups (Control, Model, Test-L, Test-M, and Test-H). SCI was induced using the method described by Allen's. Motor function of the hindlimbs was evaluated on days 1, 7, 14, 21, and 28 after the injury using the motor rating test on the Basso mouse scale (BMS). 7 days after SCI, the levels of TNF-α, IL-1β, and IL-6 were measured by enzyme-linked immunosorbent assay (ELISA); the level of NO was evaluated by Griess assay; and Western blot was used to verify the levels of proteins in the TAK1 pathway. Expressions of GFAP positive cells in injured spinal cord were detected by immunohistochemical staining.. The experiment showed that curcumin markedly inhibited SCI-induced production of inflammatory mediators, including TNF-α, IL-1β, IL-6 (ELISA assay) and nitrite oxide (Griess method) in a concentration-dependent manner. Curcumin decreased the phosphorylation levels of TGF-β-activated kinase 1 (TAK1) protein, leading to decreased phosphorylation levels of MKK6 and p38 MAPKs, key players in the microglia-mediated inflammatory response. Curcumin also significantly down-regulated the expression levels of the NF-κB upstream regulators IκB and IκB kinase (IKK). Additionally, behavior research showed that curcumin-treated mice showed significantly improved functional recovery compared to untreated mice (BMS assay). The expressions of GFAP increased in the injured spinal cord segments, which were decreased by Teat-M and Teat-H at 7d after SCI.. Curcumin restores mice hind-limb function that has been reduced by SCI. This occurs by inhibition of TAK1/MKK6/p38MAPK via the TAK1 and NFκB pathways and inflammation. These results suggest the therapeutic potential for curcumin in the treatment of SCI.

Topics: Animals; Curcumin; Female; Gene Expression Regulation; Inflammation; MAP Kinase Kinase Kinases; Mice; Spinal Cord Injuries

Subarachnoid hemorrhage (SAH)-induced cerebral vasospasm and early brain injury is a fatal clinical syndrome. Cerebral vasospasm and early brain injury are associated with inflammatory response and oxidative stress. Whether curcumin, which plays important roles to regulate inflammatory cytokines and inhibit oxidative stress, inhibits SAH-induced inflammation and oxidative stress are largely unknown.. Adult male rats underwent autologous blood injection into prechiasmatic cistern to induce SAH. Curcumin (150 mg/kg) was administered at 0.5, 24 and 48 hr post-SAH. Mortality calculation and neurological outcomes as well as morphological vasospasm of anterior cerebral artery were studied. Superoxide dismutase, lipid peroxidation, and inflammatory cytokines (MCP-1 and TNF-α) expression in prefrontal region were quantified. Furthermore, p65 and phosphor-p65 were quantitatively analyzed.. Curcumin remarkedly reduced mortality and ameliorated neurological deficits after SAH induction (. Curcumin can inhibit SAH-induced inflammatory response via restricting NF-κB activation to alleviate cerebral vasospasm and early brain injury.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Curcumin; Cytokines; Disease Models, Animal; Inflammation; Male; NF-kappa B; Oxidative Stress; Rats; Rats, Sprague-Dawley; Signal Transduction; Subarachnoid Hemorrhage; Vasospasm, Intracranial

Several studies have indicated that neuroinflammation is indeed associated with neurodegenerative disease pathology. However, failures of recent clinical trials of anti-inflammatory agents in neurodegenerative disorders have emphasized the need to better understand the complexity of the neuroinflammatory process in order to unravel its link with neurodegeneration. Deregulation of Cyclin-dependent kinase 5 (Cdk5) activity by production of its hyperactivator p25 is involved in the formation of tau and amyloid pathology reminiscent of Alzheimer's disease (AD). Recent studies show an association between p25/Cdk5 hyperactivation and robust neuroinflammation. In addition, we recently reported the novel link between the p25/Cdk5 hyperactivation-induced inflammatory responses and neurodegenerative changes using a transgenic mouse that overexpresses p25 (p25Tg). In this study, we aimed to understand the effects of early intervention with a potent natural anti-inflammatory agent, curcumin, on p25-mediated neuroinflammation and the progression of neurodegeneration in p25Tg mice. The results from this study showed that curcumin effectively counteracted the p25-mediated glial activation and pro-inflammatory chemokines/cytokines production in p25Tg mice. Moreover, this curcumin-mediated suppression of neuroinflammation reduced the progression of p25-induced tau/amyloid pathology and in turn ameliorated the p25-induced cognitive impairments. It is widely acknowledged that to treat AD, one must target the early-stage of pathological changes to protect neurons from irreversible damage. In line with this, our results demonstrated that early intervention of inflammation could reduce the progression of AD-like pathological outcomes. Moreover, our data provide a rationale for the potential use of curcuminoids in the treatment of inflammation associated neurodegenerative diseases.

Topics: Alzheimer Disease; Animals; Anti-Inflammatory Agents; Astrocytes; Brain; Calcium-Calmodulin-Dependent Protein Kinase Type 2; Curcumin; Humans; Inflammation; Memory Disorders; Mice, Inbred C57BL; Mice, Inbred CBA; Mice, Transgenic; Nerve Degeneration; Neuroimmunomodulation; Neuroprotective Agents; Nootropic Agents

The purpose of the present experiment was to investigate whether hexahydrocurcumin (HHC) attenuates brain damage and improves functional outcome via the activation of antioxidative activities, anti-inflammation, and anti-apoptosis following cerebral ischemia/reperfusion (I/R). In this study, rats with cerebral I/R injury were induced by a transient middle cerebral artery occlusion (MCAO) for 2 h, followed by reperfusion. The male Wistar rats were randomly divided into five groups, including the sham-operated, vehicle-treated, 10 mg/kg HHC-treated, 20 mg/kg HHC-treated, and 40 mg/kg HHC-treated I/R groups. The animals were immediately injected with HHC by an intraperitoneal administration at the onset of cerebral reperfusion. After 24 h of reperfusion, the rats were tested for neurological deficits, and the pathology of the brain was studied by 2,3,5-triphenyltetrazolium chloride (TTC) staining, hematoxylin and eosin (H&E) staining, and terminal deoxynucleotidyltransferase UTP nick end labeling (TUNEL) staining. In addition, the brain tissues were prepared for protein extraction for Western blot analysis, a malondialdehyde (MDA) assay, a nitric oxide (NO) assay, a superoxide dismutase (SOD) assay, a glutathione (GSH) assay, and a glutathione peroxidase (GSH-Px) assay. The data revealed that the neurological deficit scores and the infarct volume were significantly reduced in the HHC-treated rats at all doses compared to the vehicle group. Treatment with HHC significantly attenuated oxidative stress and inflammation, with a decreased level of MDA and NO and a decreased expression of NF-κB (p65) and cyclooxygenase-2 (COX-2) in the I/R rats. HHC also evidently increased Nrf2 (nucleus) protein expression, heme oxygenase-1 (HO-1) protein expression, the antioxidative enzymes, and the superoxide dismutase (SOD) activity. Moreover, the HHC treatment also significantly decreased apoptosis, with a decrease in Bax and cleaved caspase-3 and an increase in Bcl-XL, which was in accordance with a decrease in the apoptotic neuronal cells. Therefore, the HHC treatment protects the brain from cerebral I/R injury by diminishing oxidative stress, inflammation, and apoptosis. The antioxidant properties of HHC may play an important role in improving functional outcomes and may offer significant neuroprotection against I/R damage.

Topics: Animals; Antioxidants; Curcumin; Disease Models, Animal; Inflammation; Rats; Reperfusion Injury; Stroke

Topics: Apoptosis; Cell Line; Curcumin; Humans; Inflammation; Oxidative Stress; Paraquat; Reactive Oxygen Species; Superoxide Dismutase

To investigate the effects of curcumin on motor function, and to explore the neuroprotective mechanism of curcumin after the spinal cord injury in rats. The study will theoretical and experimental evidence for curcumin's clinical treatment.. HI-0400 spinal cord impactor was used to prepare animal models of acute of spinal cord injury. One hundred and five clean and healthy rats were randomly divide into three groups:sham operation group (Sham) spinal cord injury group (SCI) and curcumin group (SCI+CUR). Intragastric administration was administrated after 30min of the spinal cord injury model, after 1 time a day, until the death. SCI+CUR group was intragastric administration with curcumin (100 mg/kg) of 0.5% carboxymethyl cellulose sodium, and Sham and SCI group were treated with the same dose of 0.5% carboxymethyl cellulose sodium. The motor function recovery of 3,7,14,21 and 28 days after spinal cord injury were evaluated by basso,beatlie,bresnahan (BBB) score. The spinal cord tissue and blood samples were collected at postoperative 12 h, 1 d, 3 d and 7 d respectively, NF-kappa B was detected by immunofluorescence, Bcl-2, Bax and Caspase-3 were detected by immunohistochemistry. The expression of Bcl-2 and Bax was detected by Elisa.. The statistic difference of BBB score between SCI group and CUR group in 3 day was not statistically significant. It was found that the 7,14,21 and 28 days BBB score in CUR group were statistically significant higher than that in SCI group(. Curcumin can promote the recovery of hindlimb motor function after spinal cord injury in rats.The mechanism is through inhibition of NF-K B to prevent inflammation; And inhibition the expression of Bax and Caspase-3, and promotion the expression of Bcl-2 to prevent apoptosis, so as to accelerate the recovery of motor function in the rats after spinal cord injury.

Topics: Animals; Apoptosis; Curcumin; Inflammation; Random Allocation; Rats; Rats, Sprague-Dawley; Recovery of Function; Spinal Cord; Spinal Cord Injuries

Periodontal disease is the most common chronic inflammatory disease known to mankind (and the major cause of tooth loss in the adult population) and has also been linked to various systemic diseases, particularly diabetes mellitus. Based on the literature linking periodontal disease with diabetes in a "bidirectional manner", the objectives of the current study were to determine: (i) the effect of a model of periodontitis, complicated by diabetes, on mechanisms of tissue breakdown including bone loss; and (ii) the response of the combination of this local and systemic phenotype to a novel pleiotropic matrix metalloproteinase inhibitor, chemically modified curcumin (CMC) 2.24.. Diabetes was induced in adult male rats by intravenous injection of streptozotocin (nondiabetic rats served as controls), and Escherichia coli endotoxin (lipopolysaccharide) was repeatedly injected into the gingiva to induce periodontitis. CMC 2.24 was administered by oral gavage (30 mg/kg) daily; untreated diabetic rats received vehicle alone. After 3 wk of treatment, the rats were killed, and gingiva, jaws, tibia and skin were collected. The maxillary jaws and tibia were dissected and radiographed. The gingival tissues of each experimental group (n = 6 rats/group) were pooled, extracted, partially purified and, together with individual skin samples, analyzed for matrix metalloproteinase (MMP)-2 and MMP-9 by gelatin zymography; MMP-8 was analyzed in gingival and skin tissue extracts, and in serum, by western blotting. The levels of three bone-resorptive cytokines [interleukin (IL)-1β, IL-6 and tumor necrosis factor-α], were measured in gingival tissue extracts and serum by ELISA.. Systemic administration of CMC 2.24 to diabetic rats with endotoxin-induced periodontitis significantly inhibited alveolar bone loss and attenuated the severity of local and systemic inflammation. Moreover, this novel tri-ketonic phenylaminocarbonyl curcumin (CMC 2.24) appeared to reduce the pathologically excessive levels of inducible MMPs to near-normal levels, but appeared to have no significant effect on the constitutive MMPs required for physiologic connective tissue turnover. In addition to the beneficial effects on periodontal disease, induced both locally and systemically, CMC 2.24 also favorably affected extra-oral connective tissues, skin and skeletal bone.. This study supports our hypothesis that CMC 2.24 is a potential therapeutic pleiotropic MMP inhibitor, with both intracellular and extracellular effects, which reduces local and systemic inflammation and prevents hyperglycemia- and bacteria-induced connective tissue destruction.

Topics: Alveolar Process; Animals; Anti-Inflammatory Agents; Connective Tissue; Curcumin; Diabetes Mellitus, Experimental; Disease Models, Animal; Gingiva; Inflammation; Male; Matrix Metalloproteinase 2; Matrix Metalloproteinase 8; Matrix Metalloproteinase 9; Periodontitis; Rats; Rats, Sprague-Dawley; Skin

Curcumin, a major bioactive component of turmeric, has diverse therapeutic effects such as anti-inflammatory, antioxidant, anticancer, and antinociceptive activities. The acid-sensing ion channels (ASICs), which can be activated by acute drops in the extracellular pH, play an important role in nociception. However, very little is known about the interaction between ASICs and curcumin in nociception of inflammation. In our study, we investigated whether the antinociceptive effects of curcumin are mediated via ASICs using an orofacial nociceptive model and in vitro western blotting, immunofluorescence, whole-cell patch-clamp recordings in the trigeminal system. Intraperitoneally administered curcumin at a dose of 50 mg/kg can reduce hyperalgesia in both the phases of a formalin-induced orofacial nociceptive model. Curcumin reduced the amplitude of ASICs currents in a dose-dependent manner in trigeminal ganglion (TG) neurons, and curcumin also reduced the protein quantity but did not change the distribution of ASICs in TG. Thus, our results indicate that curcumin can reduce formalin-induced ASICs activation and thus inhibit ASICs-mediated inflammatory pain hypersensitivity.

Topics: Acid Sensing Ion Channels; Action Potentials; Animals; Curcumin; Disease Models, Animal; Face; Formaldehyde; Ganglia, Spinal; Inflammation; Neurons; Nociception; Rats, Sprague-Dawley; Trigeminal Ganglion

The most common question asked by patients with inflammatory bowel disease (IBD) is, "Doctor, what should I eat?" Findings from epidemiology studies have indicated that diets high in animal fat and low in fruits and vegetables are the most common pattern associated with an increased risk of IBD. Low levels of vitamin D also appear to be a risk factor for IBD. In murine models, diets high in fat, especially saturated animal fats, also increase inflammation, whereas supplementation with omega 3 long-chain fatty acids protect against intestinal inflammation. Unfortunately, omega 3 supplements have not been shown to decrease the risk of relapse in patients with Crohn's disease. Dietary intervention studies have shown that enteral therapy, with defined formula diets, helps children with Crohn's disease and reduces inflammation and dysbiosis. Although fiber supplements have not been shown definitively to benefit patients with IBD, soluble fiber is the best way to generate short-chain fatty acids such as butyrate, which has anti-inflammatory effects. Addition of vitamin D and curcumin has been shown to increase the efficacy of IBD therapy. There is compelling evidence from animal models that emulsifiers in processed foods increase risk for IBD. We discuss current knowledge about popular diets, including the specific carbohydrate diet and diet low in fermentable oligo-, di-, and monosaccharides and polyols. We present findings from clinical and basic science studies to help gastroenterologists navigate diet as it relates to the management of IBD.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Crohn Disease; Curcumin; Diet; Diet Therapy; Dietary Fats; Dietary Fiber; Dietary Supplements; Dysbiosis; Emulsifying Agents; Fatty Acids, Omega-6; Fatty Acids, Volatile; Fermentation; Fruit; Gastrointestinal Microbiome; Humans; Inflammation; Inflammatory Bowel Diseases; Risk Factors; Vegetables; Vitamin D Deficiency

Spinal cord injury (SCI) leads to glial scar formation by astrocytes, which severely hinders neural regeneration. Curcumin (cur) can inhibit glial scar formation, but the underlying mechanism is not fully understood. Using both in vivo and in vitro experiments, the current study investigated the phenotypic transformation of astrocytes following cur and siRNA intervention during the processes of inflammation and fibrosis and determined details of the relationship between cur treatment and the glial scar components GFAP and CSPG. We found that cur and NF-κb p65 siRNA could inhibit astrocyte activation through suppressing NF-κb signaling pathway, which led to down-regulate the expression of chemokines MCP-1, RANTES and CXCL10 released by astrocytes and decreased macrophage and T-cell infiltration, thus reducing the inflammation in the glial scar. In addition, silencing SOX-9 may reduce the deposition of extracellular matrix CSPG; whereas its over-expression could increase the CSPG expression. Cur suppressedSOX-9-inducedCSPG deposition, reduced α-SMA (an important symbol of fibrosis) expression in astrocytes, altered astrocyte phenotype, and inhibited glial scar formation by regulating fibrosis. This study confirmed that cur could regulate both the NF-κb and SOX9 signaling pathways and reduce the expression of intracellular and extracellular glial scar components through dual-target regulating both inflammation and fibrosis after SCI in the rat. This study provides an important hypothesis centered on the dual inhibition of intracellular and extracellular glial scar components as a treatment strategy for SCI.

Topics: Actins; Animals; Anti-Inflammatory Agents, Non-Steroidal; Astrocytes; Cicatrix; Curcumin; Disease Models, Animal; Extracellular Matrix; Female; Fibrosis; Inflammation; Macrophages; Random Allocation; Rats, Sprague-Dawley; RNA, Small Interfering; SOX9 Transcription Factor; Spinal Cord Injuries; T-Lymphocytes; Transcription Factor RelA

Pulmonary fibrosis is associated with irreversible, or partially reversible, airflow obstruction and ultimately unresponsiveness to asthma therapies such as corticosteroids. Intranasal curcumin, an anti-inflammatory molecule, has been found effective in allergic asthma. To study the effect of intranasal curcumin on airway remodeling and fibrosis in murine model of chronic asthma, BALB/c mice were sensitized to ovalbumin (OVA) and exposed to OVA aerosol (2%) from day 21 (after sensitization) for 5 weeks (twice/week). Curcumin (intranasal) was administered during the OVA aerosol challenge. Mice exposed to OVA developed inflammation dominated by eosinophils which lead to fibrosis and airway remodeling. Intranasal administration of curcumin significantly inhibited airway inflammation and pulmonary fibrosis, where MMP-9 activities were decreased along with α-smooth muscle actin (α-SMA), MMP-9, TIMP-1, and eotaxin expressions. These results suggest that intranasal curcumin regulates airway inflammation and remodeling in chronic asthma.

Topics: Actins; Administration, Intranasal; Airway Remodeling; Animals; Asthma; Chronic Disease; Curcumin; Eosinophils; Inflammation; Matrix Metalloproteinase 9; Mice; Ovalbumin; Pulmonary Fibrosis; Tissue Inhibitor of Metalloproteinase-1

Cancer patients often show a wasting syndrome for which there are little therapeutic options. Dietary polyphenols have been proposed for treating this syndrome, but their usefulness in cases associated with human papillomavirus (HPV)-induced cancers is unknown. We characterized HPV16-transgenic mice as a model of cancer cachexia and tested the efficacy of long-term oral supplementation with polyphenols curcumin and rutin. Both compounds were orally administered to six weeks-old HPV16-transgenic mice showing characteristic multi-step skin carcinogenesis, for 24weeks. Skin lesions and blood, liver and spleen inflammatory changes were characterized histologically and hematologically. Hepatic oxidative stress, skeletal muscle mass and the levels of muscle pro-inflammatory transcription factor NF-κB were also assessed. Skin carcinogenesis was associated with progressive, severe, systemic inflammation (leukocytosis, hepatitis, splenitis), significant mortality and cachexia. Curcumin and rutin totally suppressed mortality while reducing white blood cells and the incidence of splenitis and hepatitis. Rutin prevented muscle wasting more effectively than curcumin. Preservation of muscle mass and reduced hepatic inflammation were associated with down-regulation of the NF-κB canonical pathway and with reduced oxidative stress, respectively. These results point out HPV16-transgenic mice as a useful model for studying the wasting syndrome associated with HPV-induced cancers. Dietary NF-κB inhibitors may be useful resources for treating this syndrome.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Cachexia; Curcumin; Female; Human papillomavirus 16; Humans; Inflammation; Mice, Transgenic; Muscle, Skeletal; NF-kappa B; Rutin; Skin; Skin Neoplasms; Wasting Syndrome

The neurologic manifestations of neonatal hyperbilirubinemia in the central nervous system (CNS) exhibit high variations in the severity and appearance of motor, auditory and cognitive symptoms, which is suggestive of a still unexplained selective topography of bilirubin-induced damage. By applying the organotypic brain culture (OBC: preserving in vitro the cellular complexity, connection and architecture of the in vivo brain) technique to study hyperbilirubinemia, we mapped the regional target of bilirubin-induced damage, demonstrated a multifactorial toxic action of bilirubin, and used this information to evaluate the efficacy of drugs applicable to newborns to protect the brain. OBCs from 8-day-old rat pups showed a 2-13 fold higher sensitivity to bilirubin damage than 2-day-old preparations. The hippocampus, inferior colliculus and cerebral cortex were the only brain regions affected, presenting a mixed inflammatory-oxidative mechanism. Glutamate excitotoxicity was appreciable in only the hippocampus and inferior colliculus. Single drug treatment (indomethacin, curcumin, MgCl

Topics: Animals; Bilirubin; Brain; Brain Diseases, Metabolic; Cell Survival; Curcumin; Encephalitis; Hyperbilirubinemia; Indomethacin; Inflammation; Magnesium Chloride; Models, Biological; Neuroprotective Agents; Organ Culture Techniques; Oxidative Stress; Rats

Inflammatory bowel disease (IBD) such as Crohn's disease and ulcerative colitis is a chronic autoimmune disease affecting nearly five million people worldwide. Among all drug delivery system, oral administration is the most preferable route for colon-specific targeting and the treatment of IBD. Herein, an amphiphilic curcumin polymer (PCur) composed of hydrophilic poly(ethylene glycol) (PEG) and hydrophobic curcumin (Cur) linked by disulfide bond was synthesized and characterized. The sufficient solubility, nano-scaled size and close to the neutral surface potential of PCur lead to preferential accumulation of the active drug in the inflamed regions of the gut. Moreover, PCur showed limited drug release and enhanced robustness under the physiological pH of the gastrointestinal tract (GIT), and a significantly elevated release was observed when responding to a bacterial reduction in the colon. Furthermore, cellular studies confirmed PCur had low cytotoxicity and increased transmembrane permeability, resulting in improved oral bioavailability evidenced by in vivo pharmacokinetics of rats. Finally, with DSS-induced murine model of IBD, we demonstrated that orally administered PCur ameliorated the inflammatory progression in the colon and could protect mice from IBD. In conclusion, it is illustrated that the developed PCur conjugate could potentially be employed as a colon-specific candidate for IBD treatment.

Topics: Administration, Oral; Animals; Bacteria; Caco-2 Cells; Cell Line, Tumor; Colon; Curcumin; Drug Carriers; Drug Delivery Systems; Female; Humans; Hydrophobic and Hydrophilic Interactions; Inflammation; Inflammatory Bowel Diseases; Mice; Mice, Inbred C57BL; Particle Size; Permeability; Polyethylene Glycols; Polymers; Rats; Rats, Sprague-Dawley

The nutritional curcumin (CUR) is beneficial in cell-mediated autoimmune diseases. The molecular mechanisms underlying this food-mediated silencing of inflammatory immune responses are poorly understood. By investigating antigen-specific immune responses we found that dietary CUR impairs the differentiation of Th1/Th17 cells in vivo during encephalomyelitis and instead promoted Th2 cells. In contrast, feeding CUR had no inhibitory effect on ovalbumin-induced airway inflammation. Mechanistically, we found that CUR induces an anti-inflammatory phenotype in dendritic cells (DC) with enhanced STAT3 phosphorylation and suppressed expression of Il12b and Il23a. On the molecular level CUR readily induced NRF2-sensitive heme oxygenase 1 (HO-1) mRNA and protein in LPS-activated DC. HO-1 enhanced STAT3 phosphorylation, which enriched to Il12b and Il23a loci and negatively regulated their transcription. These findings demonstrate the underlying mechanism through which a nutritional can interfere with the immune response. CUR silences IL-23/Th17-mediated pathology by enhancing HO-1/STAT3 interaction in DC.

Topics: Animals; Autoimmune Diseases; Curcumin; Dendritic Cells; Encephalomyelitis, Autoimmune, Experimental; Heme Oxygenase-1; Immunity, Cellular; Inflammation; Interleukin-23; Membrane Proteins; Mice; Ovalbumin; Phosphorylation; STAT3 Transcription Factor; Th17 Cells; Th2 Cells

A series of novel multipotent 2-piperidone derivatives were designed, synthesized and biologically evaluated as chemical agents for the treatment of Alzheimer's disease (AD). The results showed that most of the target compounds displayed significant potency to inhibit Aβ(1-42) self-aggregation. Among them, compound 7q exhibited the best inhibition of Aβ(1-42) self-aggregation (59.11% at 20 μM) in a concentration-dependent manner. Additionally, the compounds 6b, 7p and 7q as representatives were found to present anti-inflammation properties in lipopolysaccharide (LPS)-induced microglial BV-2 cells. They could effectively suppress the production of pro-inflammatory cytokines such as TNF-α, IL-1β and IL-6. Meanwhile, compound 7q could prevent the neuronal cell SH-SY5Y death by LPS-stimulated microglia cell activation mediated neurotoxicity. The molecular modeling studies demonstrated that compounds matched the pharmacophore well and had good predicted physicochemical properties and estimated IC50 values. Moreover, compound 7q exerted a good binding to the active site of myeloid differentiation factor 88 (MyD88) through the docking analysis and could interfere with its homodimerization or heterodimerization. Consequently, these compounds emerged as promising candidates for further development of novel multifunctional agents for AD treatment.

Topics: Amyloid beta-Peptides; Animals; Anti-Inflammatory Agents, Non-Steroidal; Cell Death; Cell Line; Dose-Response Relationship, Drug; Drug Design; HEK293 Cells; Humans; Immunoprecipitation; Inflammation; Lipopolysaccharides; Mice; Molecular Docking Simulation; Molecular Structure; Neurons; Peptide Fragments; Piperidones; Protein Aggregates; Protein Binding; Structure-Activity Relationship

To observe the protective effect of different doses of curcumin on hepatocytes of rats with sepsis.. 100 healthy male Sprague-Dawley (SD) rats were randomly divided into sham operation group, sepsis group, and low, medium, high dose curcumin intervention groups (L-cur, M-cur, H-cur groups), with 20 rats in each group. The animal model of sepsis was reproduced by cecal ligation and puncture (CLP) method, and in the sham operation group the cecum was just taken out and returned. In the L-cur, M-cur, H-cur groups curcumin was immediately injected after CLP with a dose of 50, 100, 150 mg/kg, respectively, and the rats in sham operation group and sepsis group were given the same amount of normal saline. Five rats in each group were sacrificed at 2, 6, 12, 24 hours after operation, and the hepatic tissues and blood samples were obtained. The pathological changes in hepatic tissues were observed under a microscope, and hepatocytes apoptosis and apoptosis index (AI) of hepatocytes were determined with transferase-mediated deoxyuridine triphosphate-biotin nick end labeling (TUNEL) method, and the levels of serum procalcitonin (PCT), tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) were determined with enzyme linked immunosorbent assay (ELISA) method.. Microscopic examination showed that the damage degree of hepatic tissues was significantly increased in sepsis group; the number of apoptotic cells and damage degree of hepatic tissues were increased gradually over time. The damage degree of hepatic tissues in curcumin groups was lessened as compared with sepsis group, especially in M-cur group. There were no significant changes in AI and serum PCT, TNF-α, and IL-1β levels at any of the time points tested in the sham operation group. The AI, serum PCT, TNF-α, and IL-1β levels in the sepsis group were significantly higher than those in the sham operation group from 2 hours after operation on [AI: (23.59±2.00)% vs. (2.02±0.13)%, PCT (μg/L): 2.41±0.21 vs. 0.81±0.01, TNF-α (ng/L): 217.28±14.24 vs. 80.02±2.26, IL-1β (ng/L): 61.84±3.21 vs. 25.78±1.29, all P < 0.05], and they showed a gradually increasing tendency. AI reached peak value at 24 hours after operation [(52.05±1.31)%]; PCT, TNF-α and IL-1β reached the peak values at 12 hours after operation [(8.68±0.58) μg/L, (314.13±14.39) ng/L, (132.24±2.58) ng/L, respectively]. Curcumin intervention significantly reduced the levels of AI, TNF-α, PCT and IL-1β in hepatocytes of septic rats, especially in M-cur group [AI: (11.56±0.96)% vs. (23.59±2.00)% at 2 hours, (30.35±1.20)% vs. (52.05±1.31)% at 24 hours; PCT (μg/L): 1.13±0.19 vs. 2.41±0.21 at 2 hours, 5.09±0.42 vs. 8.68±0.58 at 12 hours; TNF-α (ng/L): 124.73±7.47 vs. 217.28±14.24 at 2 hours, 168.68±6.95 vs. 314.13±14.39 at 12 hours; IL-1β (ng/L): 35.05±1.00 vs. 61.84±3.21 at 2 hours, 84.06±3.42 vs. 132.24±2.58 at 12 hours; all P < 0.05].. Curcumin can inhibit the inflammatory reaction of hepatocytes of rats, prevent apoptosis, and protect the hepatocytes of rats with sepsis. The concentration of curcumin with the most significant effect is 100 mg/kg, which is the medium dosage.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Apoptosis; Calcitonin; Curcumin; Disease Models, Animal; Hepatocytes; Inflammation; Interleukin-1beta; Liver; Male; Random Allocation; Rats; Rats, Sprague-Dawley; Sepsis; Tumor Necrosis Factor-alpha

Multiple Organ Dysfunction Syndrome (MODS) is characterized as progressive and uncontrolled inflammatory response which involves activation of inflammatory cascades, cytokines release, and endothelial dysfunction, leading to deterioration of several organ functions. Curcumin is a natural polyphenol related to the yellow color of turmeric and has been reported to exert an anti-inflammatory, anti-oxidative, and anti-tumor effect. We conducted the study to investigate the effects of curcumin in non-septic MODS caused by zymosan in mice model.. The mice were randomly allocated into five groups (six mice per group): control group (treated with physiological saline, 0.1 mL daily for 3 days before and 1 h after physiological saline treatment), DMSO group (treated with DMSO, 0.1 mL daily for 3 days before and 1 h after physiological saline treatment), Curcumin group (200 mg/kg, suspended in DMSO, in a final volume of 0.1 mL, used for 3 days daily before and 1 h after physiological saline treatment), Zymosan+DMSO group (treated with DMSO, 0.1 mL daily for 3 days before and 1 h after zymosan treatment) and Zymosan+ Curcumin group (treated with curcumin, suspended in DMSO at a dose of 0.1 mL daily for 3 days before and 1 h after zymosan treatment).Mice in groups were sacrificed, and then the blood and tissues were collected to evaluate the severity of acute peritonitis, tissue histopathological changes, NO formation, oxidative stress, PMN infiltration, cytokines production, organ function, and NF-κB activation 18 h after when zymosan or physiological saline was injected. In another set of experiments, the mice were also grouped (20 mice per group) for monitoring the loss of body weight and mortality for 7 days after zymosan or physiological saline administration.. Curcumin induces a significant reduction of the volume exudate and the neutrophil infiltration. It also could exhibit an outstanding protective effect against histopathological injury by decreasing the NO formation, oxidative stress, cytokines production, and infiltration of inflammatory cells. The organ function is also improved by administration of curcumin. Moreover, the activation of NF-κB is attenuated by curcumin in the MODS mice model, suggesting that curcumin attenuated the zymosan-induced MODS via inhibiting the expression of NF-κB possibly. In addition, curcumin-treated mice were shown to alleviate the severity of MODS characterized by a minor systemic toxicity, less body weight loss, and lower mortality caused by zymosan administration.. Curcumin attenuates zymosan-induced MODS.

Topics: Animals; Anti-Infective Agents; Curcumin; Inflammation; Male; Mice; Mice, Inbred C57BL; Multiple Organ Failure; Zymosan

The effects of curcumin (CCM) on cerebral ischemia/reperfusion injury are not well understood. The aim of this study was to investigate whether CCM attenuates inflammation and mitochondrial dysfunction in a rat model of cerebral ischemia/reperfusion injury and whether Sirt1 is involved in these potential protective effects. Sirtinol, a Sirt1 inhibitor, was used to elucidate the underlying mechanism. Rats were subjected to 2h of transient middle cerebral artery occlusion (MCAO), followed by reperfusion for 24h. Brain magnetic resonance imaging (MRI) was used to detect infarct volumes. Neurological scores and brain water content were also assessed. Levels of tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6) in the brain were detected using commercial enzyme-linked immunosorbent assay (ELISA) kits. Expression of SIRT1, acetylated p53 (Ac-p53), Bcl-2, and Bax was measured by western blotting. Our results suggested that CCM exerted a neuroprotective effect, as shown by reduced infarct volumes and brain edema and improved neurological scores. CCM also exerted anti-inflammatory effects, as indicated by decreased TNF-α and IL-6 levels in the brain. CCM elevated mitochondrial membrane potential, mitochondrial complex I activity, and mitochondrial cytochrome c levels, but reduced cytosolic cytochrome c levels. Moreover, CCM upregulated SIRT1 and Bcl-2 expression and downregulated Ac-p53 and Bax expression. These effects of CCM were abolished by sirtinol. In conclusion, our results demonstrate that CCM treatment attenuates ischemic stroke-induced brain injury via activation of SIRT1.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Brain Edema; Curcumin; Disease Models, Animal; Drug Administration Schedule; Gene Expression Regulation; Histocompatibility Antigens Class I; Infarction, Middle Cerebral Artery; Inflammation; Male; Membrane Potential, Mitochondrial; Mitochondrial Diseases; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species; Reperfusion Injury; Signal Transduction; Sirtuin 1

Emerging evidence suggests that high fructose consumption may be a potentially important factor responsible for the rising incidence of insulin resistance and diabetes worldwide. The present study investigated the preventive effect of curcumin on inflammation, oxidative stress and insulin resistance in high fructose fed male Wistar rats at the molecular level. Fructose feeding for 10 weeks caused oxidative stress, inflammation and insulin resistance. Curcumin treatment attenuated the insulin resistance by decreasing IRS-1 serine phosphorylation and increasing IRS-1 tyrosine phosphorylation in the skeletal muscle of high fructose fed rats. It also attenuated hyperinsulinemia, glucose intolerance and HOMA-IR level. Curcumin administration lowered tumor necrosis factor alpha (TNF-α), C reactive protein (CRP) levels and downregulated the protein expression of cyclo-oxygenase 2 (COX-2), protein kinase theta (PKCθ). In addition, inhibitor κB alpha (IκBα) degradation was prevented by curcumin supplementation. Treatment with curcumin inhibited the rise of malondialdehyde (MDA), total oxidant status (TOS) and suppressed the protein expression of extracellular kinase ½ (ERK ½), p38 in the skeletal muscle of fructose fed rats. Further, it enhanced Glutathione Peroxidase (GPx) activity in the muscle of fructose fed rats. At the molecular level, curcumin inhibited the activation of stress sensitive kinases and inflammatory cascades. Our findings conclude that curcumin attenuated glucose intolerance and insulin resistance through its antioxidant and anti-inflammatory effects. Thus, we suggest the use of curcumin as a therapeutic adjuvant in the management of diabetes, obesity and their associated complications.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Curcumin; Fructose; Glucose Intolerance; Glucose Tolerance Test; Inflammation; Insulin Resistance; Male; Oxidative Stress; Phosphorylation; Protein Serine-Threonine Kinases; Rats; Rats, Wistar; Structure-Activity Relationship

Methylglyoxal (MGO)-induced carbonyl stress and pro-inflammatory responses have been suggested to contribute to endothelial dysfunction. Curcumin (Cur), a polyphenolic compound from Curcuma longa L., may protect endothelial cells against carbonyl stress-induced damage by trapping dicarbonyl compounds such as MGO. However, Cur-MGO adducts have not been studied in depth to date and it remains to be known whether Cur-MGO adducts are able to attenuate endothelial damage by trapping MGO. In the present study, 1,2-diaminobenzene was reacted with MGO to ensure the reliability of the reaction system. Cur was demonstrated to trap MGO at a 1:1 ratio to form adducts 1, 2 and 3 within 720 min. The structures of these adducts were identified by high-performance liquid chromatography/electrospray ionization tandem mass spectrometry. The kinetic curves of Cur (10(-7), 10(-6) and 10(-5) M) were measured from 0-168 h by fluorescent intensity. Cur significantly inhibited the formation of advanced glycation end products (AGEs). The differences in oxidative damage and the levels of pro-inflammatory cytokines following MGO + HSA or Cur-MGO treatment were investigated in human umbilical vein endothelial cells (HUVECs). Exposure of HUVECs to the Cur-MGO reaction adducts significantly reduced the intracellular ROS levels and improved cell viability compared with MGO alone. Furthermore, there was a significant reduction in the expression levels of transforming growth factor-β1 and intercellular adhesion molecule(-1) following treatment with Cur-MGO adducts compared with MGO alone. These results provide further evidence that the trapping of MGO by Cur inhibits the formation of AGEs. The current study indicates that the protective effect of Cur on carbonyl stress and pro-inflammatory responses in endothelial damage occurs via the trapping of MGO.

Topics: Cell Death; Cell Survival; Chromatography, High Pressure Liquid; Curcumin; Glycation End Products, Advanced; Human Umbilical Vein Endothelial Cells; Humans; Inflammation; Intercellular Adhesion Molecule-1; Oxidative Stress; Pyruvaldehyde; Reactive Oxygen Species; Spectrometry, Mass, Electrospray Ionization; Transforming Growth Factor beta1; Up-Regulation

Our previous data demonstrated that nuclear factor-κB (NF-κB) and activator protein-1 (AP-1) are involved in the process of anti-β2GPI/β2GPI-induced tissue factor (TF) expression in monocytes. However, the role of NF-κB and AP-1 in pathogenic mechanisms of antiphospholipid syndrome (APS) in vivo has been rarely studied. This study aimed to investigate whether NF-κB and c-Jun/AP-1 are involved in anti-β2GPI-induced expression of prothrombotic and proinflammatory molecules in mouse. IgG-APS or anti-β2GPI antibodies were injected into BALB/c mice in the presence or absence of PDTC (a specific inhibitor of NF-κB) and Curcumin (a potent inhibitor of AP-1) treatment. Our data showed that both IgG-APS and anti-β2GPI could induce the activation of NF-κB and c-Jun/AP-1 in mouse peritoneal macrophages. The anti-β2GPI-induced TF activity in homogenates of carotid arteries and peritoneal macrophages from mice could significantly decrease after PDTC and/or Curcumin treatment, in which PDTC showed the strongest inhibitory effect, but combination of two inhibitors had no synergistic effect. Furthermore, anti-β2GPI-induced expression of TF, VCAM-1, ICAM-1 and E-selectin in the aorta and expression of TF, IL-1β, IL-6 and TNF-α in peritoneal macrophages of mice were also significantly attenuated by PDTC and/or Curcumin treatment. These results indicate that both NF-κB and c-Jun/AP-1 are involved in regulating anti-β2GPI-induced expression of prothrombotic and proinflammatory molecules in vivo. Inhibition of NF-κB and c-Jun/AP-1 pathways may be beneficial for the prevention and treatment of thrombosis and inflammation in patients with APS.

Topics: Animals; Antibodies; Antiphospholipid Syndrome; beta 2-Glycoprotein I; Curcumin; E-Selectin; Immunoglobulin G; Inflammation; Intercellular Adhesion Molecule-1; Interleukin-1beta; Interleukin-6; Macrophages, Peritoneal; Male; Mice, Inbred BALB C; NF-kappa B; Phosphorylation; Proline; Real-Time Polymerase Chain Reaction; Thiocarbamates; Thromboplastin; Thrombosis; Transcription Factor AP-1; Tumor Necrosis Factor-alpha; Vascular Cell Adhesion Molecule-1

The present study investigated the beneficial effects of curcumin on inflammation, oxidative stress and insulin resistance in high-fat fed male Wistar rats.. Five-month-old male Wistar rats (n=20) were divided into two groups (10 rats in each group). Among the two groups, one group received 30 % high-fat diet (HFD) and another group received 30 % HFD with curcumin (200 mg/kg body weight). Food intake, body weight and biochemical parameters were measured at the beginning and at the end of the study. After 10 weeks, oxidative stress parameters in skeletal muscle and hepatic triacylglycerol (TAG) content were estimated. Histological examinations of the liver samples were performed at the end of the experiment.. High-fat feeding caused increase in body weight, liver and adipose tissue mass. Rats fed with HFD showed increased levels of fasting plasma glucose, insulin, Homeostasis Model Assessment for Insulin resistance (HOMA-IR), total cholesterol (TC), TAG, very low density lipoprotein cholesterol (VLDL-c) and decreased high-density lipoprotein cholesterol (HDL-c). There was also increase in the plasma inflammatory markers [tumor necrosis factor-α (TNF-α), C-reactive protein (CRP)] and skeletal muscle oxidative stress parameters [malondialdehyde (MDA), total oxidant status (TOS)] in these rats. In addition, high-fat feeding increased liver TAG content and caused fat accumulation in the liver. Treatment with curcumin significantly reduced body weight, relative organ weights (liver, adipose tissue), glucose, insulin and HOMA-IR. Curcumin supplementation decreased plasma levels of TC, TAG, VLDL-c, TNF-α and increased HDL-c. Administration of curcumin also reduced MDA, TOS in skeletal muscle, hepatic TAG content and liver fat deposition.. Curcumin supplementation improved HFD-induced dyslipidemia, oxidative stress, inflammation and insulin resistance.

Topics: Adipose Tissue; Animals; Blood Glucose; Body Weight; Cholesterol; Curcumin; Diet, High-Fat; Dietary Supplements; Fasting; Inflammation; Inflammation Mediators; Insulin; Insulin Resistance; Liver; Male; Muscle, Skeletal; Obesity; Oxidative Stress; Rats; Rats, Wistar; Triglycerides

The aim of the study was to investigate the ameliorative effects of curcumin on fibrinogen like protein-2 (fgl-2), some oxido-inflammatory and apoptotic markers in rat-induced acute pancreatitis (AP). Seventy-five albino rats were divided into control group, l-arginine (l-Arg)-induced AP group, curcumin pre-treated group before AP induction, curcumin post-treated group after AP induction, and curcumin injected group only. AP group showed severe necrotizing pancreatitis confirmed by histopathological changes and elevations in serum amylase and lipase activities, levels of epithelial neutrophil-activating peptide 78, tissue content of protein carbonyls, levels of tumor necrosis factor α, and caspase-3 as well as myeloperoxidase activity. Significant elevation in pancreatic fgl-2 mRNA expression was detected in AP group. Improvement of all parameters was detected with increase of caspase-3 in both curcumin-treated groups that confirmed curcumin ameliorative effects against AP through induction of apoptosis and inhibition of micro-thrombosis, inflammation, and oxidative stress.

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Arginine; Caspase 3; Curcumin; Disease Models, Animal; Fibrinogen; Gene Expression Regulation; Inflammation; Injections, Intraperitoneal; Male; Oxidative Stress; Pancreatitis, Acute Necrotizing; Peroxidase; Protein Carbonylation; Rats; Rats, Sprague-Dawley; RNA, Messenger; Tumor Necrosis Factor-alpha

To evaluate the response of cells to boron nitride nanotubes (BNNTs) carrying fluorescent probes or drugs in their inner channel by assessment of the cellular localization of the fluorescent cargo, evaluation of the in vitro release and biological activity of a drug (curcumin) loaded in BNNTs.. Cells treated with curcumin-loaded BNNTs and stimulated with lipopolysaccharide were assessed for nitric oxide release and stimulation of IL-6 and TNF-α. The cellular trafficking of two cell-permeant dyes and a non-cell-permeant dye loaded within BNNTs was imaged.. BNNTs loaded with up to 13 wt% fluorophores were internalized by cells and controlled release of curcumin triggered cellular pathways associated with the known anti-inflammatory effects of the drug.. The overall findings indicate that BNNTs can function as nanocarriers of biologically relevant probes/drugs allowing one to examine/control their local intracellular localization and biochemical effects, leading the way to applications as intracellular nanosensors.

Topics: Boron Compounds; Curcumin; Drug Carriers; Drug Delivery Systems; Fluorescence; Humans; Inflammation; Interleukin-6; Nanotubes; Nitric Oxide; Tumor Necrosis Factor-alpha

Diets rich in fruits and vegetables (FV), which contain (poly)phenols, protect against age-related inflammation and chronic diseases. T-lymphocytes contribute to systemic cytokine production and are modulated by FV intake. Little is known about the relative potency of different (poly)phenols in modulating cytokine release by lymphocytes. We compared thirty-one (poly)phenols and six (poly)phenol mixtures for effects on pro-inflammatory cytokine release by Jurkat T-lymphocytes. Test compounds were incubated with Jurkat cells for 48 h at 1 and 30 µm, with or without phorbol ester treatment at 24 h to induce cytokine release. Three test compounds that reduced cytokine release were further incubated with primary lymphocytes at 0·2 and 1 µm for 24 h, with lipopolysaccharide added at 5 h. Cytokine release was measured, and generation of H2O2 by test compounds was determined to assess any potential correlations with cytokine release. A number of (poly)phenols significantly altered cytokine release from Jurkat cells (P<0·05), but H2O2 generation did not correlate with cytokine release. Resveratrol, isorhamnetin, curcumin, vanillic acid and specific (poly)phenol mixtures reduced pro-inflammatory cytokine release from T-lymphocytes, and there was evidence for interaction between (poly)phenols to further modulate cytokine release. The release of interferon-γ induced protein 10 by primary lymphocytes was significantly reduced following treatment with 1 µm isorhamnetin (P<0·05). These results suggest that (poly)phenols derived from onions, turmeric, red grapes, green tea and açai berries may help reduce the release of pro-inflammatory mediators in people at risk of chronic inflammation.

Topics: Cell Survival; Chronic Disease; Curcuma; Curcumin; Cytokines; Euterpe; Female; Humans; Hydrogen Peroxide; Inflammation; Jurkat Cells; Lipopolysaccharides; Lymphocytes; Middle Aged; Onions; Polyphenols; Quercetin; Resveratrol; Stilbenes; Tea; Vanillic Acid; Vitis

Diabetic nephropathy is a serious complication of type 2 diabetes mellitus, and delaying the development of diabetic nephropathy in patients with diabetes mellitus is very important. In this study, we investigated inflammation, oxidative stress, and lipid metabolism to assess whether curcumin ameliorates diabetic nephropathy.. Animals were divided into three groups: Long-Evans-Tokushima-Otsuka rats for normal controls, Otsuka-Long-Evans-Tokushima Fatty (OLETF) rats for the diabetic group, and curcumin-treated (100 mg/kg/day) OLETF rats. We measured body and epididymal fat weights, and examined plasma glucose, adiponectin, and lipid profiles at 45 weeks. To confirm renal damage, we measured albumin-creatinine ratio, superoxide dismutase (SOD), and malondialdehyde (MDA) in urine samples. Glomerular basement membrane thickness and slit pore density were evaluated in the renal cortex tissue of rats. Furthermore, we conducted adenosine monophosphate-activated protein kinase (AMPK) signaling and oxidative stress-related nuclear factor (erythroid-derived 2)-like 2 (Nrf2) signaling to investigate mechanisms of lipotoxicity in kidneys.. Curcumin ameliorated albuminuria, pathophysiologic changes on the glomerulus, urinary MDA, and urinary SOD related with elevated Nrf2 signaling, as well as serum lipid-related index and ectopic lipid accumulation through activation of AMPK signaling.. Collectively, these findings indicate that curcumin exerts renoprotective effects by inhibiting renal lipid accumulation and oxidative stress through AMPK and Nrf2 signaling pathway.

Topics: Albuminuria; Animals; Anti-Inflammatory Agents, Non-Steroidal; Curcumin; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Gene Expression; Inflammation; Kidney; Kidney Glomerulus; Lipid Metabolism; Male; Malondialdehyde; Oxidative Stress; Rats; Rats, Inbred OLETF; Rats, Long-Evans; Superoxide Dismutase

Curcumin and emu oil derived from emu bird (Dromaius novaehollandiae) has shown promising results against inflammation. However, the delivery of curcumin is hindered due to low solubility and poor permeation. In addition, till date the role of emu oil in drug delivery has not been explored systemically. Hence, the current investigation was designed to evaluate the anti-inflammatory potential of curcumin in combination with emu oil from a nanoemulgel formulation in experimental inflammation and arthritic in vivo models. Nanoemulsion was prepared using emu oil, Cremophor RH 40 and Labrafil M2125CS as oil phase, surfactant and co-surfactant. The optimized curcumin loaded nanoemulsion with emu oil was incorporated into carbopol gel for convenient application by topical route. The anti-inflammatory efficacy was evaluated in carrageenan induced paw edema and FCA induced arthritic rat model in terms of paw swelling, weight indices of the liver and spleen, pathological changes in nuclear factor kappa B, iNOS, COX-2 expression and inflammatory cytokines. Arthritic scoring, paw volume, biochemical, molecular, radiological and histological examinations indicated significant improvement in anti-inflammatory activity with formulations containing curcumin in combination with emu oil compared to pure curcumin. These encouraging results demonstrate the potential of formulations containing curcumin and emu oil combination in rheumatoid arthritis.

Topics: Administration, Topical; Animals; Anti-Inflammatory Agents; Arthritis, Experimental; Carrageenan; Chemistry, Pharmaceutical; Curcumin; Disease Models, Animal; Drug Delivery Systems; Edema; Emulsions; Excipients; Inflammation; Male; Nanoparticles; Oils; Rats; Rats, Sprague-Dawley; Solubility

The molecular mechanism of curcumin in macrophage polarization remains unknown in renal failure. We examined, whether curcumin treatment is associated with the modulation of renal function and macrophage phenotype switch in daunorubicin (DNR) induced nephrotoxicity model. Sprague-Dawley rats were treated with a cumulative dose of 9mg/kg DNR (i.v). Followed by curcumin (100mg/kg) administration orally every day for 6weeks. DNR treated rats showed nephrotoxicity as evidenced by worsening renal function, which was assessed by measuring creatinine and blood urea nitrogen in serum. These changes were reversed by treatment with curcumin, which resulted in significant improvement in renal function. Furthermore, curcumin increased cluster of differentiation (CD)163 expression, and down-regulated renal expression of antigen II type I receptor (AT1R), endothelin (ET)1, ET receptor type A and B (ETAR and ETBR), CD68 and CD80. Renal protein expression of extracellular signal-regulated kinase (ERK)1/2 and nuclear factor (NF)κB p65 were increased in DNR treated rats, and treatment with curcumin attenuated these increased expression. Curcumin mediated a further increase in the levels of interleukin (IL)-10. In addition, the expression of M1 phenotype was increased in DNR treated rats, which were attenuated by curcumin. Taken together, our results demonstrated that polyphenol curcumin has an ability to improve renal function and might induce the phenotypic switching from M1 to M2 macrophage polarization in DNR induced nephrotoxicity in rats.

Topics: Animals; Blood Urea Nitrogen; Creatinine; Curcumin; Daunorubicin; Down-Regulation; Inflammation; Interleukin-10; Kidney; Kidney Function Tests; Macrophages; Male; Rats; Rats, Sprague-Dawley; Renal Insufficiency; Tetraspanin 30

Increased molecular understanding of multifactorial diseases paves the way for novel therapeutic approaches requiring sophisticated carriers for intracellular delivery of actives. We designed and characterized self-assembling lipid-core nanocapsules for coencapsulation of two poorly soluble natural polyphenols curcumin and resveratrol. The polyphenols were identified as high-potential therapeutic candidates intervening in the intracellular inflammation cascade of chondrocytes during the progress of osteoarthritis. To elucidate the interplay between chondrocytes and nanocapsules and their therapeutic effect, we pursued a complementary analytical approach combining label-free visualization with biological assays. Primary human chondrocytes did not show any adverse effects upon nanocapsule application and coherent anti-Stokes Raman scattering images visualized their intracellular uptake. Further, by systematically blocking different uptake mechanisms, an energy independent uptake into the cells could be identified. Additionally, we tested the therapeutic effect of the polyphenol-loaded carriers on inflamed chondrocytes. Treatment with nanocapsules resulted in a major reduction of nitric oxide levels, a well-known apoptosis trigger during the course of osteoarthritis. For a more profound examination of this protective effect on joint cells, we pursued studies with atomic force microscopy investigations. Significant changes in the cell cytoskeleton as well as prominent dents in the cell membrane upon induced apoptosis were revealed. Interestingly, these effects could not be detected for chondrocytes which were pretreated with the nanocapsules. Overall, besides presenting a sophisticated carrier system for joint application, these results highlight the necessity of establishing combinatorial analytical approaches to elucidate cellular uptake, the interplay of codelivered drugs and their therapeutic effect on the subcellular level.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Chondrocytes; Curcumin; Drug Carriers; Grape Seed Extract; Humans; Inflammation; Microscopy, Atomic Force; Nanocapsules; Nonlinear Optical Microscopy; Particle Size; Polyphenols; Polysorbates; Resveratrol; Stilbenes; Vitis

The potential toxicity of quinocetone (QCT) has raised widely concern, but its mechanism is still unclear. This study aimed to investigate the protective effect of curcumin on QCT induced apoptosis and the underlying mechanism in human hepatocyte L02 cells. The results showed that QCT treatment significantly decreased the cell viability of L02 cell and increased the release of lactate dehydrogenase (LDH), which was attenuated by curcumin pre-treatment at 1.25, 2.5 and 5 μM. Compared to the QCT alone group, curcumin pre-treatment significantly attenuated QCT induced oxidative stress, mitochondrial dysfunction and apoptosis. In addition, curcumin pretreatment markedly attenuated QCT-induced increase of iNOS activity and NO production in a dose-dependent manner. Meanwhile, curcumin pretreatment markedly down-regulated the expression of nuclear factor -kB (NF-kB) and iNOS mRNAs, but up-regulated the expressions of Nrf2 and HO-1 mRNAs, compared to the QCT alone group. Zinc protoporphyrin IX, a HO-1 inhibitor, markedly partly abolished the cytoprotective effect of curcumin against QCT-induced caspase activation, NF-kB mRNA expression. These results indicate that curcumin could effectively inhibit QCT induced apoptosis and inflammatory response in L02 cells, which may involve the activation of Nrf2/HO-1 and inhibition of NF-kB pathway.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Antioxidants; Apoptosis; Blotting, Western; Cells, Cultured; Curcumin; Heme Oxygenase-1; Hepatocytes; Humans; Inflammation; L-Lactate Dehydrogenase; NF-E2-Related Factor 2; NF-kappa B; Nitric Oxide; Nitric Oxide Synthase Type II; Oxidative Stress; Quinoxalines; Real-Time Polymerase Chain Reaction; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger

In many liver disorders, oxidative stress-related inflammation and apoptosis are important pathogenic components, finally resulting in acute liver failure. Erythropoietin and its analogues are well known to influence the interaction between apoptosis and inflammation in brain and kidney. The study is to clarify the effect of curcumin, a natural plant phenolic food additive, on lipopolysaccharides (LPS)-induced acute liver injury of mice with endotoxemia and associated molecular mechanism from inflammation, apoptosis and oxidative stress levels. And curcumin, lowered serum cytokines, including Interleukin 1beta (IL-1β), Interleukin 6 (IL-6) and tumor necrosis factor (TNF-α), and improved liver apoptosis through suppressing phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) signaling pathway and inhibiting Cyclic AMP-responsive element-binding protein (CREB)/Caspase expression, and decreased oxidative stress-associated protein expression, mainly involving 2E1 isoform of cytochrome P450/nuclear factor E2-related factor 2/reactive oxygen species (CYP2E/Nrf2/ROS) signaling pathway, as well as liver nitric oxide (NO) production in LPS-induced mice. Moreover, curcumin regulated serum alanine transaminase (ALT), aspartate transaminase (AST) and alkaline phosphatase (ALP), accelerated liver antioxidant enzymes, such as superoxide dismutase (SOD), catalase (CAT), glutathione (GSH) and glutathione peroxidase (GSH-px) levels, and inhibited activation of the mitogen-activated protein kinases/c-Jun NH2-terminal kinase (P38/JNK) cascade in the livers of LPS-induced rats. Thus, curcumin treatment attenuates LPS-induced PI3K/AKT and CYP2E/Nrf2/ROS signaling and liver injury. Strategies to inhibit inflammation and apoptosis signaling may provide alternatives to the current clinical approaches to improve oxidative responses of endotoxemia.

Topics: Animals; Apoptosis; Curcumin; Hepatic Stellate Cells; Inflammation; JNK Mitogen-Activated Protein Kinases; Lipopolysaccharides; Liver Failure; Male; Mice, Inbred C57BL; NF-kappa B; Oxidative Stress; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Reactive Oxygen Species; RNA, Messenger; Sepsis; Signal Transduction

Liver fibrosis is concomitant with monocyte infiltration, which has been highlighted as novel therapeutic targets for chronic liver diseases. We aimed to investigate whether curcumin might protect the liver from carbon tetrachloride (CCl4)-induced fibrosis by attenuating the recruitment of Gr1hi monocytes through inhibition of monocyte chemoattractant protein-1 (MCP-1).. Mice were intraperitoneally injected with CCl4 to induce liver fibrosis. Curcumin was orally administrated to mice. Hepatic inflammation and fibrosis were evaluated by analysis of liver function and hepatic histopathology. Infiltration of the Gr1hi monocytes was assessed by flow cytometry and immunohistochemistry. Moreover, mRNA expression levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-1β, and transforming growth factor (TGF)-β1 were determined by real time PCR. Hepatic expression of MCP-1 was determined by real time PCR and immunohistochemistry.. Curcumin significantly attenuated inflammation and fibrosis, as revealed by histological and biochemical analysis. The intrahepatic infiltration of Gr1hi monocytes was attenuated by curcumin administration. T cells, NK cells, NKT cells, and dendritic cells were not affected by curcumin. Curcumin significantly reduced the expression of TNF-α and TGF-β1, which is in line with the decreased numbers of intrahepatic Gr1hi monocytes. Intrahepatic MCP-1 expression of CCl4-challenged mice was inhibited by curcumin.. The anti-inflammatory and antifibrotic effects of curcumin could be contributed to its prevention of Gr1hi monocyte infiltration into the injured livers through inhibition of MCP-1. These new findings extend our understanding on the mechanisms of the anti-inflammatory and antifibrotic effects of curcumin.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Antigens, Ly; Carbon Tetrachloride; Chemokine CCL2; Curcumin; Disease Models, Animal; Flow Cytometry; Humans; Immunohistochemistry; Inflammation; Liver; Liver Cirrhosis; Male; Mice; Mice, Inbred C57BL; Monocytes; Transforming Growth Factor beta1; Tumor Necrosis Factor-alpha

Cholestasis is a clinically significant symptom and widely associated with liver diseases, however, there are very few effective therapies for cholestasis. Danning tablet (DNT, a Chinese patent medicine preparation) has been clinically used to treat human liver and gallbladder diseases for more than 20 years in China. However, which ingredients of DNT contributed to this beneficial effect and their mechanistic underpinnings have been largely unknown. In the present study, we discovered that DNT not only demonstrated greater benefits for cholecystitis patients after cholecystectomy surgery in clinic but also showed protective effect against alpha-naphthylisothiocyanate (ANIT)-induced cholestasis model in rodent. Curcumin, one major compound derived from DNT, exerted the protective effect against cholestasis through farnesoid X receptor (FXR), which has been focused as potential therapeutic targets for treating cholestasis. The underlying mechanism of curcumin against cholestasis was restoring bile acid homeostasis and antagonizing inflammatory responses in a FXR-dependent manner and in turn contributed to overall cholestasis attenuation. Collectively, curcumin can be served as a potential treatment option for liver injury with cholestasis.

Topics: 1-Naphthylisothiocyanate; Animals; Bile Acids and Salts; Cholestasis; Curcumin; Disease Models, Animal; HEK293 Cells; Humans; Inflammation; Mice; Mice, Knockout; Receptors, Cytoplasmic and Nuclear

Curcumin has several biological functions particularly antioxidant and anti-inflammatory. The aims of this study are determination of the protective effects of curcumin on cisplatin-induced renal tubular cell apoptosis and related pathways in kidney. Eighteen male Wistar albino rats were randomly divided into three groups (n = 6): the control, cisplatin (CP), and cisplatin + curcumin (CP + CUR). Acute renal damage was induced by single dose of cisplatin (7.5 mg/kg) injected by intraperitoneally (i.p). The animals of curcumin-treated group were received daily 200 mg/kg curcumin per os (po), starting from 2 days before the injection of cisplatin to the day of sacrifice. Forty-eight hours after cisplatin injection, samples of cardiac blood and kidneys were harvested from the animals. In this study, the major finding is that curcumin treatment ameliorates the following conditions associated with cisplatin-induced nephrotoxicity: (1) the development of kidney injury (histopathology), (2) inflammatory responses [myeloperoxidase (MPO) and tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), IL-6, IL-10 levels], (3) the degree of lipid peroxidation [malondialdehyde (MDA) level], (4) renal tubular cell apoptosis (active caspase-3) and expression of related proteins [p53, Fas, and Fas ligand (Fas-L)] by immunohistochemistry, (5) renal dysfunction (serum urea and creatinine). In a conclusion, this study suggests that curcumin has antiapoptotic effect against cisplatin nephrotoxicity, in addition to anti-inflammatory and antioxidant properties.

Topics: Acute Kidney Injury; Animals; Anti-Inflammatory Agents, Non-Steroidal; Apoptosis; Blood Urea Nitrogen; Cisplatin; Creatinine; Curcumin; Cytokines; Inflammation; Kidney; Lipid Peroxidation; Male; Oxidative Stress; Random Allocation; Rats; Rats, Wistar

In the present study, a new series of 2-amino-pyran-3-carbonitrile derivatives of curcumin 2-7 have been synthesized via one-pot simple and efficient protocol, involving the reaction of curcumin 1 with substituted-benzylidene-malononitrile to modify the 1,3-diketone moiety. The structures of the synthesized compounds 2-7 were elucidated by microanalytical and spectral data, which were found consistent with the assigned structures. The nephroprotective mechanism of these new curcumin analogues was evaluated on the post-gamma-irradiation (7 Gy) - induced nephrotoxicity in rats. Activation of Nrf2 by these curcumin analogues is responsible for the amendment of the antioxidant status, impairment of NF-κB signal, thus attenuate the nephrotoxicity induced post-γ-irradiation exposure. 4-Chloro-phenyl curcumin analogue 7 showed the most potent activity. In conclusion, the results of the present study demonstrate a promising role of these new curcumin analogues to attenuate the early symptoms of nephrotoxicity induced by γ-irradiation in rats via activation of Nrf2 gene expression. These new curcumin analogues need further toxicological investigations to assess their therapeutic index.

Topics: Animals; Antioxidants; Biomarkers; Blotting, Western; Caspase 3; Curcumin; DNA Fragmentation; Electrophoresis, Agar Gel; Gamma Rays; Gene Expression Regulation; Inflammation; Intercellular Adhesion Molecule-1; Kidney; Kidney Diseases; Kidney Function Tests; Male; NF-E2-Related Factor 2; Nitric Oxide Synthase Type II; Rats; Stereoisomerism; Trace Elements; Vascular Cell Adhesion Molecule-1

Topics: Antineoplastic Agents; Curcumin; Humans; Inflammation; Neoplasms

This study analyzed the physicochemical and photophysical properties of essential oil of Curcuma longa and its angiogenic potential. The results showed that curcumin is the main fluorescent component present in the oil, although the amount is relatively small. The experimental chorioallantoic membrane model was used to evaluate angiogenic activity, showing a significant increase in the vascular network of Curcuma longa and positive control groups when compared to the neutral and inhibitor controls (P <0.05), but no significant difference was found between Curcuma longa essential oil and the positive control (P >0.05). Histological analysis showed extensive neovascularization, hyperemia and inflammation in the positive control group and Curcuma longa when compared to other controls (P <0.05), characteristic factors of the angiogenesis process. In conclusion, Curcuma longa oil showed considerable proangiogenic activity and could be a potential compound in medical applications.

Topics: Angiogenesis Inducing Agents; Animals; Chickens; Chorioallantoic Membrane; Curcuma; Curcumin; Hyperemia; Inflammation; Neovascularization, Physiologic; Oils, Volatile; Plant Oils

Combination therapy is an emerging strategy that is under intensive preclinical investigation for the treatment of various diseases. CD98 is highly overexpressed on the surfaces of epithelial cells and macrophages in the colon tissue with ulcerative colitis (UC), which is usually associated with mucosal damage and inflammation. We previously proved that CD98 siRNA (siCD98)-induced down-regulation of CD98 in colitis tissue decreased the severity of UC to a certain extent. In an effort to further improve the therapeutic efficacy, we aim to simultaneously deliver siCD98 in combination with a potent anti-inflammatory agent, curcumin (CUR), using hyaluronic acid (HA)-functionalized polymeric nanoparticles (NPs). The resultant spherical HA-siCD98/CUR-NPs are featured by a desirable particle size (∼246 nm) and slightly negative zeta potential (∼-14 mV). The NPs functionalized with HA are able to guide the co-delivery of drugs to the targeted cells related to UC therapy (colonic epithelial cells and macrophages). Compared to either siCD98- or CUR-based monotherapy, co-delivery of siCD98 and CUR by HA-functionalized NPs can exert combinational effects against UC by protecting the mucosal layer and alleviating inflammation both

Topics: Administration, Oral; Animals; Anti-Inflammatory Agents; Biological Products; Cell Line; Colitis, Ulcerative; Colon; Curcumin; Drug Carriers; Drug Therapy, Combination; Epithelial Cells; Fusion Regulatory Protein-1; Hyaluronic Acid; Inflammation; Intestinal Mucosa; Lactic Acid; Macrophages; Male; Mice; Molecular Targeted Therapy; Nanoparticles; Polyglycolic Acid; Polylactic Acid-Polyglycolic Acid Copolymer; RNA, Small Interfering; Treatment Outcome

Curcumin is among the most promising dietary compounds for cancer prevention. However, curcumin rapidly degrades in aqueous buffer at physiological pH, making it difficult to understand whether the effects of curcumin are from curcumin itself or its degradation products. Here we studied the antiproliferative and anti-inflammatory effects of curcumin degradation products, including its total degradation products (a mixture containing all stable degradation products of curcumin) and bicyclopentadione (a dominant stable degradation compound of curcumin). Curcumin potently modulated cell proliferation, progression of cell cycle, and apoptosis in MC38 colon cancer cells and inhibited lipopolysaccharide (LPS)-induced inflammatory responses and NF-κB signaling in RAW 264.7 macrophage cells. In contrast, neither the total degradation products of curcumin nor bicyclopentadione had such effects. For example, after 24 h of treatment in MC38 colon cancer cells, 5 μg/mL curcumin inhibited 39.2 ± 1.8% of cell proliferation, whereas its degradation products were inactive. Together, these results suggest that the stable chemical degradation products of curcumin are not likely to play a major role in mediating the biological activities of curcumin.

Topics: Animals; Anti-Inflammatory Agents; Antineoplastic Agents; Apoptosis; Cell Cycle; Cell Line, Tumor; Cell Proliferation; Curcumin; Inflammation; Lipopolysaccharides; Macrophages; Mice; Molecular Structure; NF-kappa B; RAW 264.7 Cells; Signal Transduction

A novel series of clioquinol-moracin hybrids were designed and synthesized by fusing the pharmacophores of clioquinol and moracin M, and their activities as multitarget-directed ligands against Alzheimer's disease were evaluated. Biological activity results demonstrated that these hybrids possessed significant inhibitory activities against phosphodiesterase 4D (PDE4D) and Aβ aggregation as well as remarkable antioxidant effects and excellent blood-brain barrier permeability. The optimal compound, 18d (WBQ5187), exhibited excellent PDE4D inhibitory potency (IC50 = 0.32 μM), significant antioxidant effects, appropriate biometal chelating functions, and interesting properties that modulated self- and metal-induced Aβ aggregation. Two-dimensional NMR studies revealed that 18d had significant interactions with Aβ1-42 at the R5, H6, H14, Q15, and F20 residues. Furthermore, this typical hybrid possessed preeminent neuroprotective effects against inflammation in microglial cells. Most importantly, oral administration of 18d·HCl demonstrated marked improvements in cognitive and spatial memory in a rat model of Alzheimer's disease and protected hippocampal neurons from necrosis.

Topics: Alzheimer Disease; Amyloid beta-Peptides; Animals; Antioxidants; Benzofurans; Clioquinol; Cognition; Cyclic Nucleotide Phosphodiesterases, Type 4; Inflammation; Ligands; Male; Memory; Models, Molecular; Neurons; Neuroprotective Agents; Phosphodiesterase 4 Inhibitors; Protein Aggregates; Rats; Rats, Wistar; Resorcinols

The anti-atherogenic potentials of total ginger (Zingiber officinale) extract (TGE) or curcuminoids extracted from turmeric (Curcuma longa), members of family Zingiberaceae, were compared in hypercholesterolaemia. Rabbits were fed either normal or atherogenic diet. The rabbits on atherogenic diet received treatments with TGE or curcumenoids and placebo concurrently for 6 weeks (n = 6). The anti-atherogenic effects of curcuminoids and ginger are mediated via multiple mechanisms. This effect was correlated with their ability to lower cholesteryl ester transfer protein activity. Ginger extract exerted preferential effects on plasma lipids, reverse cholesterol transport, cholesterol synthesis and inflammatory status. Curcuminoids, however, showed superior antioxidant activity.

Topics: Animals; Antioxidants; Cholesterol Ester Transfer Proteins; Curcuma; Curcumin; Diet, Atherogenic; Disease Models, Animal; Hypercholesterolemia; Hypolipidemic Agents; Inflammation; Liver; Oxidative Stress; Plant Extracts; Rabbits; Zingiber officinale

Curcumin has diverse biological activities including antioxidant and anti-inflammatory activity. However, its clinical use for topical application is limited due to its poor aqueous solubility and thus, minimal cutaneous bioavailability. Elastic vesicles (EVs) of curcumin were prepared to improve its cutaneous bioavailability and to use it for topical anti-inflammatory effect. Ex vivo skin permeation and retention studies were performed to check if incorporation of curcumin into EVs could improve its permeation into and retention in the skin. Evaluation of acute and chronic anti-inflammatory effect was done using xylene-induced acute ear edema in mice and cotton pellet-induced chronic inflammation in rats, respectively. A significant improvement in flux (nine times) across murine skin was observed when aqueous dispersion of curcumin (flux - 0.46 ± 0.02 μg/h/cm(2)) was compared with curcumin-loaded EVs (flux - 4.14 ± 0.04 μg/h/cm(2)). Incorporation of these curcumin-loaded EVs into a hydrophilic ointment base resulted in higher skin retention (51.66%) in contrast to free curcumin ointment (1.64%) and a marketed formulation (VICCO® turmeric skin cream). The developed ointment showed an effect similar (p < 0.05) to the marketed diclofenac sodium ointment (Omni-gel®) in suppression of acute inflammation in mouse; a significant inhibition (28.8% versus 3.91% for free curcumin) of cotton pellet-induced chronic inflammation was also observed. Thus, curcumin-loaded EVs incorporated in hydrophilic ointment is a promising topical anti-inflammatory formulation.

Topics: Administration, Cutaneous; Animals; Anti-Inflammatory Agents; Biological Availability; Chemistry, Pharmaceutical; Curcumin; Dermatologic Agents; Diclofenac; Drug Carriers; Edema; Female; Hydrophobic and Hydrophilic Interactions; Inflammation; Male; Mice; Ointments; Permeability; Rats; Rats, Wistar; Skin; Skin Absorption; Solubility

Curcumin has been confirmed to have anti-inflammatory properties in addition to the ability to decrease the expression of pro-inflammatory cytokines in keratinocytes. It was suggested that the interleukin-23 (IL-23)/IL-17A cytokine axis played a critical role in the pathogenesis of 12-O-tetradecanoyl phorbol 12-myristate 13-acetate (TPA)-induced K14-VEGF transgenic psoriasis-like mice model. Here, we report that topical use of a curcumin gel formulation inhibited TPA-induced Th1 inflammation in K14-VEGF transgenic mice ears but not Th17 inflammation as expected. Real-time PCR showed that mRNA levels of IL-23, IL-17A, IL-22, IL-6 and TNFα cytokines failed to increase after TPA-induction in K14-VEGF transgenic mice ear skin; but the mRNA level of IFNγ increased significantly at the same time. Furthermore, TPA-induction up-regulated the TCRγδ protein but failed to impact the CCR6 protein, which means that the proliferation of γδ T cells is incapable of IL-17A production. We find that curcumin is capable of relieving TPA-induced inflammation by directly down-regulating IFNγ production. In conclusion, curcumin inhibits TPA-induced Th1 inflammation in K14-VEGF transgenic mice which has not been previously described.

Topics: Animals; Anti-Inflammatory Agents; Curcumin; Cytokines; Disease Models, Animal; Gels; Inflammation; Mice, Transgenic; Nuclear Receptor Subfamily 1, Group F, Member 3; Psoriasis; Receptors, Antigen, T-Cell, gamma-delta; Receptors, CCR6; RNA, Messenger; Skin; Tetradecanoylphorbol Acetate; Th1 Cells

Curcumin, a natural polyphenol compound, has been widely reported for diverse pharmacological effects and already been investigated for eye diseases. However, the water-insolubility of curcumin and the inherent penetration barriers in cornea make it difficult for curcumin to enter eye. This work aimed to develop ion-sensitive curcumin-loaded Pluronic P123 (P123)/D-a-tocopheryl polyethylene glycolsuccinate (TPGS) mixed micelle in situ gels (CUR-MM-ISGs) to prolong ocular retention time and improve cornea permeability. Central composite design-response surface methodology was applied for the optimization of curcumin-loaded P123/TPGS mixed micelles (CUR-MMs). Characterization tests showed that CUR-MMs were in spherical shape with small size and low critical micelle concentration. After dispersing the micelles in gellan gum solution (0.2%, w/w) at the ratio of 3:1 and 1:1 (v/v), respectively, CUR-MM-ISGs were formed and presented transparent appearance. Sustained release profile was obtained in vitro for both CUR-MM-ISGs (3:1 or 1:1, v/v). The irritation test proved that CUR-MM-ISGs as ophthalmic formulations were gentle and biocompatible towards ocular tissues. In addition, the ex vivo corneal penetration study indicated that the cumulative drug permeation amount of CUR-MM-ISGs (3:1, v/v) was respectively 1.16-fold and 1.32-fold higher than CUR-MM-ISGs (1:1, v/v) and curcumin solution. It can be concluded from these results that the developed ion-sensitive mixed micelle in situ gel system is a potential ophthalmic delivery carrier for curcumin as a poorly soluble drug.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Biological Transport; Cornea; Curcumin; Drug Carriers; Drug Liberation; Factor Analysis, Statistical; Hydrophobic and Hydrophilic Interactions; Inflammation; Irritants; Kinetics; Male; Micelles; Particle Size; Permeability; Poloxalene; Polyethylene Glycols; Polysaccharides, Bacterial; Rabbits; Sodium Dodecyl Sulfate; Solubility; Vitamin E; Water

Nanoscale drug delivery platforms have been developed over the past four decades that have shown promising clinical results in several types of cancer and inflammatory disorders. These nanocarriers carrying therapeutic payloads are maximizing the therapeutic outcomes while minimizing adverse effects. Yet one of the major challenges facing drug developers is the dilemma of premature versus on-demand drug release, which influences the therapeutic regiment, efficacy and potential toxicity. Herein, we report on redox-sensitive polymer-drug conjugate micelles for on-demand intracellular delivery of a model active agent, curcumin. Biodegradable methoxy poly(ethylene glycol)-poly(lactic acid) copolymer (mPEG-PLA) was conjugated with curcumin via a disulfide bond or ester bond (control), respectively. The self-assembled redox-sensitive micelles exhibited a hydrodynamic size of 115.6 ± 5.9 (nm) with a zeta potential of -10.6 ± 0.7 (mV). The critical micelle concentration was determined at 6.7 ± 0.4 (μg mL(-1)). Under sink conditions with a mimicked redox environment (10 mM dithiothreitol), the extent of curcumin release at 48 h from disulfide bond-linked micelles was nearly three times higher compared to the control micelles. Such rapid release led to a lower half maximal inhibitory concentration (IC50) in HeLa cells at 18.5 ± 1.4 (μg mL(-1)), whereas the IC50 of control micelles was 41.0 ± 2.4 (μg mL(-1)). The cellular uptake study also revealed higher fluorescence intensity for redox-sensitive micelles. In conclusion, the redox-sensitive polymeric conjugate micelles could enhance curcumin delivery while avoiding premature release, and achieving on-demand release under the high glutathione concentration in the cell cytoplasm. This strategy opens new avenues for on-demand drug release of nanoscale intracellular delivery platforms that ultimately might be translated into pre-clinical and future clinical practice.

Topics: Biocompatible Materials; Catalytic Domain; Cell Survival; Curcumin; Cytoplasm; Disulfides; Drug Carriers; Glutathione; HeLa Cells; Humans; Hydrodynamics; Hydrogen-Ion Concentration; Inflammation; Inhibitory Concentration 50; Lactates; Magnetic Resonance Spectroscopy; Micelles; Microscopy, Electron, Transmission; Molecular Weight; Nanomedicine; Nanoparticles; Nanotechnology; Oxidation-Reduction; Particle Size; Polyethylene Glycols; Polymers; Temperature

Curcumin is a major component of turmeric and reportedly has anti-inflammatory and anti-oxidant effects. Neuroinflammation has been recognized to play an important role in the pathogenesis of various diseases in the central nervous system. Here we investigated the anti-nociceptive and anti-neuroinflammatory effect of curcumin on arthritic pain in rats. We found that repeated oral treatment with curcumin, either before or after complete Freund's adjuvant (CFA) injection, dose-dependently attenuated CFA-induced mechanical allodynia and thermal hyperalgesia, but had no effect on joint edema. Repeated intrathecal injection of curcumin reversed CFA-induced pain hypersensitivity. Furthermore, such a curcumin treatment reduced CFA-induced activation of glial cells and production of inflammatory mediators [interleukin-1β (IL-1β), monocyte chemoattractant protein-1 (MCP-1), and monocyte inflammatory protein-1 (MIP-1α)] in the spinal cord. Curcumin also decreased lipopolysaccharide-induced production of IL-1β, tumor necrosis factor-α, MCP-1, and MIP-1α in cultured astrocytes and microglia. Our results suggest that intrathecal curcumin attenuates arthritic pain by inhibiting glial activation and the production of inflammatory mediators in the spinal cord, suggesting a new application of curcumin for the treatment of arthritic pain.

Topics: Analgesics; Animals; Anti-Inflammatory Agents; Antioxidants; Arthritis, Experimental; Astrocytes; Cells, Cultured; Chemokine CCL2; Chemokine CCL3; Curcumin; Hyperalgesia; Inflammation; Injections, Spinal; Interleukin-1beta; Lipopolysaccharides; Male; Microglia; Pain; Rats; Rats, Sprague-Dawley; Spinal Cord; Spine

Oral administration of nonsteroidal anti-inflammatory drugs (NSAIDs) was frequently associated with serious adverse effects. Inspired by curcumin-a naturally traditional Chinese medicine, a series of curcumin derivatives containing NSAIDs, used for transdermal application, were synthesized and screened for their anti-inflammatory activities in vitro and in vivo. Compared with curcumin and parent NSAID (salicylic acid and salsalate), topical application of A11 and B13 onto mouse ear edema, prior to TPA treatment markedly suppressed the expression of IL-1β, IL-6 and TNF-α, respectively. Mechanistically, A11 and B13 blocked the phosphorylation of IκBα and suppressed the activation of p65 and IκBα. It was found that A11 and B13 may be potent anti-inflammatory agents for the treatment of inflammatory diseases.

Topics: Administration, Topical; Animals; Anti-Inflammatory Agents, Non-Steroidal; Curcumin; Ear; Edema; Inflammation; Interleukin-1beta; Interleukin-6; Mice; NF-kappa B; Tumor Necrosis Factor-alpha

We describe a novel wound dressing (HR006) with two components: a lyophilized matrix of the galactomannan from locust bean gum (LBG) and an antioxidant hydration solution (AHsol) containing curcumin and N-acetyl-L-cysteine (NAC). Physico-structural analyses of the LBG matrix revealed homogeneous interconnected pores with high absorbing capacity showing excellent properties for moist wound care (MWC). In an in vitro oxidative stress fibroblast injury model, the AHsol showed relevant protective effects reducing intracellular reactive oxygen species (ROS) production, rescuing cell viability, and regulating expression of inflammation-related genes (COX-2, TNF-α, IL-1α, IL-1β). The new dressing showed good biocompatibility profile as demonstrated by cytotoxicity, hemocompatibility, and skin irritation tests. Moreover, in an in vivo skin wound model in pigs, this dressing enhanced the production of healthy and organized granulation tissue and re-epithelization. In summary, HR006 exhibits significant antioxidant activity, good biocompatibility, and excellent repair capabilities improving tissue remodeling and the healing of wounds.

Topics: Acetylcysteine; Animals; Antioxidants; Bandages; Curcumin; Cytokines; Fibroblasts; Galactans; Galactose; Humans; Inflammation; Irritants; Mannans; Materials Testing; Oxidative Stress; Plant Gums; Reactive Oxygen Species; Sus scrofa; Wound Healing

Parkinson's disease (PD) is the second most common neurodegenerative disease, with the prevalence increasing as the population ages. Many mechanisms have been implicated in the pathogenesis of PD including oxidative stress, mitochondrial dysfunction, protein aggregation, and inflammation. Current treatment strategies focus on symptomatic improvement. However, therapies to modify disease progression are lacking. A whole food, plant-based diet contains many compounds that fight oxidative stress and inflammation. Evidence from animal models show that various phytochemicals may alter the mechanisms contributing to PD pathophysiology. Epidemiological studies show a relationship between reduced risk of PD and diet. We hypothesize that phytochemicals in plant-based foods may contribute to neuroprotection in PD and that adopting a plant-based diet may provide symptomatic improvement and alter disease progression in PD.

Topics: Animals; Antioxidants; Curcumin; Diet; Ergothioneine; Fragaria; Humans; Inflammation; Isothiocyanates; Mitochondria; Nervous System; Neurons; Oxidative Stress; Parkinson Disease; Phytochemicals; Plants; Quercetin; Sulfoxides

CISD2 is known to have roles in calcium metabolism, anti-apoptosis, and longevity. However, whether CISD2 is involved in the inflammatory response associated with injuries of the central nervous system (CNS) remains unclear. This issue is particularly relevant for traumatic spinal cord injuries (SCIs), which lack therapeutic targeting and often cause long-term disability in patients. The authors previously demonstrated the neuroprotective effects of curcumin against RANTES-mediated neuroinflammation. In this study, we investigated (1) the role of CISD2 in injury-induced inflammation and (2) whether curcumin influences CISD2 expression in acute SCI.. The efficacy of curcumin treatment (40 mg/kg i.p.) was evaluated in an animal model of SCI. In a neural cell culture model, lipopolysaccharide (LPS) was administrated to induce inflammation with the aim of mimicking the situation commonly encountered in SCI. Additionally, knockdown of CISD2 expression by siRNA (siCISD2) in LPS-challenged neural cells was performed to verify the causal relationship between CISD2 and SCI-related inflammation.. The injuries were shown to reduce CISD2 mRNA and protein expression in vivo, and CISD2-positive cells were upregulated by the curcumin treatment. LPS led to a decrease in CISD2 expression in vitro; however, treatment with 1 μM curcumin attenuated the downregulation of CISD2. Furthermore, in a cellular model of LPS-induced injury, the loss of CISD2 function caused by siCISD2 resulted in a pronounced iNOS increase as well as a decrease in BCL2 expression.. To the best of our knowledge, this is the first study to report the following: (1) CISD2 exerts anti-apoptotic and anti-inflammatory effects in neural cells; and (2) curcumin can attenuate the downregulation of CISD2 in SCI and LPS-treated astrocytes.

Topics: Animals; Astrocytes; Autophagy-Related Proteins; Carrier Proteins; Curcumin; Disease Models, Animal; Inflammation; Male; Mice; Mice, Inbred C57BL; Nerve Tissue Proteins; Neuroprotective Agents; Nitric Oxide; Rats; Rats, Sprague-Dawley; Signal Transduction; Spinal Cord Injuries

Oxidative stress and inflammation are involved in the development and progression of diabetes and its complications. The renin-angiotensin system also plays an important role in the pathogenesis of diabetes and its complications. We hypothesized that curcumin and captopril would restore the kidney and nerve functions of diabetic rats through their angiotensin converting enzyme 1 (ACE1) inhibiting activity as well as their antioxidant and anti-inflammatory effects. Diabetes was induced by a single intraperitoneal injection of streptozotocin (100 mg·kg(-1) body weight). One week after induction of diabetes, rats were treated with 100 mg·kg(-1)·day(-1) curcumin or 50 mg·kg(-1)·day(-1) captopril orally for 6 weeks. Compared with diabetic control rats, curcumin- or captopril-treated diabetic rats had significantly improved blood glucose, lipid profile, kidney/body weight ratio, serum creatinine, blood urea nitrogen (BUN), and pain thresholds assessed by Von Frey filaments, hot plate test, and tail-flick test. Diabetic control rats showed increased levels of total peroxide, renal and neural tumor necrosis factor-α and interleukin-10, and renal ACE1 compared with nondiabetic rats. Although treatment with either curcumin or captopril restored the altered variables, captopril was more effective in reducing these variables. ACE1 was positively correlated with BUN and creatinine and negatively correlated with paw withdrawal threshold, hot plate reaction time, and tail-flick latency, suggesting a possible causal relationship. We conclude that curcumin and captopril protect against diabetic nephropathy and neuropathy by inhibiting ACE1 as well as oxidation and inflammation. These findings suggest that curcumin and captopril may have a role in the treatment of diabetic nephropathy and neuropathy.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Anti-Inflammatory Agents, Non-Steroidal; Antioxidants; Blood Glucose; Blood Urea Nitrogen; Captopril; Creatinine; Curcumin; Diabetes Mellitus, Experimental; Diabetic Nephropathies; Inflammation; Kidney; Lipids; Male; Oxidative Stress; Peptidyl-Dipeptidase A; Rats; Rats, Wistar

Lipoprotein cholesterol metabolism dysfunction in the arterial wall is a major contributor to atherosclerosis, and excessive lipid intake and failed cholesterol homeostasis may accelerate the atherogenic process. Curcumin exerts multiple effects by alleviating inflammation, hyperlipidemia, and atherosclerosis; however, its role in cholesterol transport homeostasis and its underlying impact on inflammatory M1 macrophages are poorly understood. This work aimed to investigate the effect of curcumin on cholesterol transport, the inflammatory response and cell apoptosis in M1 macrophages. RAW264.7 macrophages (M0) were induced with LPS plus IFN-γ for 12 h to develop a M1 subtype and were then incubated with curcumin at different concentrations (6.25 and 12.5 μmol/L) in the presence or absence of oxLDL. Then, cholesterol influx/efflux and foam cell formation as well as inflammation and apoptosis were evaluated. It was found that curcumin increased cholesterol uptake measured by the Dil-oxLDL binding assay, and simultaneously increased cholesterol efflux carried out by Apo-A1 and HDL in M1 cells. Curcumin further reinforced ox-LDL-induced cholesterol esterification and foam cell formation as determined by Oil Red O and BODIPY staining. Moreover, curcumin dramatically reduced ox-LDL-induced cytokine production such as IL-1β, IL-6 as well as TNF-α and M1 cell apoptosis. We also found that curcumin upregulated CD36 and ABCA1 in M1 macrophages. Curcumin increased PPARγ expression, which in turn promoted CD36 and ABCA1 expression. In conclusion, curcumin may increase the ability of M1 macrophages to handle harmful lipids, thus promoting lipid processing, disposal and removal, which may support cholesterol homeostasis and exert an anti-atherosclerotic effect.

Topics: Animals; Atherosclerosis; ATP Binding Cassette Transporter 1; Biological Transport; CD36 Antigens; Cell Line; Cholesterol; Curcumin; Esterification; Homeostasis; Inflammation; Macrophages; Mice; PPAR gamma

Dietary curcumin was studied for its potential to decrease adiposity and reverse obesity- associated cognitive impairment in a mouse model of midlife sedentary obesity. We hypothesized that curcumin intake, by decreasing adiposity, would improve cognitive function in a manner comparable to caloric restriction (CR), a weight loss regimen. 15-month-old male C57BL/6 mice were assigned in groups to receive the following dietary regimens for 12 weeks: (i) a base diet (Ain93M) fed ad libitum (AL), (ii) the base diet restricted to 70% of ad libitum (CR) or (iii) the base diet containing curcumin fed AL (1000 mg/kg diet, CURAL). Blood markers of inflammation, interleukin 6 (IL-6) and C-reactive protein (CRP), as well as an indicator of redox stress (GSH: GSSG ratio), were determined at different time points during the treatments, and visceral and subcutaneous adipose tissue were measured upon completion of the experiment. After 8 weeks of dietary treatment, the mice were tested for spatial cognition (Morris water maze) and cognitive flexibility (discriminated active avoidance). The CR group showed significant weight loss and reduced adiposity, whereas CURAL mice had stable weight throughout the experiment, consumed more food than the AL group, with no reduction of adiposity. However, both CR and CURAL groups took fewer trials than AL to reach criterion during the reversal sessions of the active avoidance task, suggesting an improvement in cognitive flexibility. The AL mice had higher levels of CRP compared to CURAL and CR, and GSH as well as the GSH: GSSG ratio were increased during curcumin intake, suggesting a reducing shift in the redox state. The results suggest that, independent of their effects on adiposity; dietary curcumin and caloric restriction have positive effects on frontal cortical functions that could be linked to anti-inflammatory or antioxidant actions.

Topics: Adiposity; Animals; Anti-Inflammatory Agents; C-Reactive Protein; Caloric Restriction; Curcumin; Disease Models, Animal; Glutathione; Humans; Inflammation; Interleukin-6; Male; Maze Learning; Mice; Obesity

The mechanism underlying pulmonary inflammation in thermal inhalation injury remains elusive. Cystic fibrosis, also hallmarked with pulmonary inflammation, is caused by mutations in CFTR, the expression of which is temperature-sensitive. We investigated whether CFTR is involved in heat-induced pulmonary inflammation. We applied heat-treatment in 16HBE14o- cells with CFTR knockdown or overexpression and heat-inhalation in rats in vivo. Heat-treatment caused significant reduction in CFTR and, reciprocally, increase in COX-2 at early stages both in vitro and in vivo. Activation of ERK/JNK, NF-κB and COX-2/PGE2 were detected in heat-treated cells, which were mimicked by knockdown, and reversed by overexpression of CFTR or VX-809, a reported CFTR mutation corrector. JNK/ERK inhibition reversed heat-/CFTR-knockdown-induced NF-κB activation, whereas NF-κB inhibitor showed no effect on JNK/ERK. IL-8 was augmented by heat-treatment or CFTR-knockdown, which was abolished by inhibition of NF-κB, JNK/ERK or COX-2. Moreover, in vitro or in vivo treatment with curcumin, a natural phenolic compound, significantly enhanced CFTR expression and reversed the heat-induced increases in COX-2/PGE2/IL-8, neutrophil infiltration and tissue damage in the airway. These results have revealed a CFTR-regulated MAPK/NF-κB pathway leading to COX-2/PGE2/IL-8 activation in thermal inhalation injury, and demonstrated therapeutic potential of curcumin for alleviating heat-induced pulmonary inflammation.

Topics: Aminopyridines; Animals; Benzodioxoles; Cell Line; Curcumin; Cyclooxygenase 2; Cystic Fibrosis Transmembrane Conductance Regulator; Dinoprostone; Enzyme-Linked Immunosorbent Assay; Extracellular Signal-Regulated MAP Kinases; Hot Temperature; Inflammation; Inhalation; Interleukin-8; JNK Mitogen-Activated Protein Kinases; Lung Diseases; Male; Microscopy, Fluorescence; Mitogen-Activated Protein Kinases; NF-kappa B; Rats; Rats, Sprague-Dawley; Real-Time Polymerase Chain Reaction; RNA Interference; RNA, Messenger; RNA, Small Interfering; Signal Transduction; Up-Regulation

Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease characterized by synovial inflammation and joint disability. Curcumin is known to be effective in ameliorating joint inflammation in RA. To obtain new insights into the effect of curcumin on primary fibroblast-like synoviocytes (FLS, N = 3), which are key effector cells in RA, we employed gas chromatography/time-of-flight mass spectrometry (GC/TOF-MS)-based metabolomics. Metabolomic profiling of tumor necrosis factor (TNF)-α-stimulated and curcumin-treated FLS was performed using GC/TOF-MS in conjunction with univariate and multivariate statistical analyses. A total of 119 metabolites were identified. Metabolomic analysis revealed that metabolite profiles were clearly distinct between TNF-α-stimulated vs. the control group (not stimulated by TNF-α or curcumin). Treatment of FLS with curcumin showed that the metabolic perturbation by TNF-α could be reversed to that of the control group to a considerable extent. Curcumin-treated FLS had higher restoration of amino acid and fatty acid metabolism, as indicated by the prominent metabolic restoration of intermediates of amino acid and fatty acid metabolism, compared with that observed in TNF-α-stimulated FLS. In particular, the abundance of glycine, citrulline, arachidonic acid, and saturated fatty acids in TNF-α-stimulated FLS was restored to the control level after treatment with curcumin, suggesting that the effect of curcumin on preventing joint inflammation may be elucidated with the levels of these metabolites. Our results suggest that GC/TOF-MS-based metabolomic investigation using FLS has the potential for discovering the mechanism of action of curcumin and new targets for therapeutic drugs in RA.

Topics: Adult; Aged; Arthritis, Rheumatoid; Cells, Cultured; Curcumin; Female; Fibroblasts; Humans; Inflammation; Metabolomics; Middle Aged; Synovial Membrane; Tumor Necrosis Factor-alpha

In the present study, the anti-atherosclerotic effect and the underlying mechanism of curcuma oil (C. oil), a lipophilic fraction from turmeric (Curcuma longa L.), was evaluated in a hamster model of accelerated atherosclerosis and in THP-1 macrophages. Male golden Syrian hamsters were subjected to partial carotid ligation (PCL) or FeCl3-induced arterial oxidative injury (Ox-injury) after 1 week of treatment with a high-cholesterol (HC) diet or HC diet plus C. oil (100 and 300 mg/kg, orally). Hamsters fed with the HC diet were analysed at 1, 3 and 5 weeks following carotid injury. The HC diet plus C. oil-fed group was analysed at 5 weeks. In hyperlipidaemic hamsters with PCL or Ox-injury, C. oil (300 mg/kg) reduced elevated plasma and aortic lipid levels, arterial macrophage accumulation, and stenosis when compared with those subjected to arterial injury alone. Similarly, elevated mRNA transcripts of matrix metalloproteinase-2 (MMP-2), MMP-9, cluster of differentiation 45 (CD45), TNF-α, interferon-γ (IFN-γ), IL-1β and IL-6 were reduced in atherosclerotic arteries, while those of transforming growth factor-β (TGF-β) and IL-10 were increased after the C. oil treatment (300 mg/kg). The treatment with C. oil prevented HC diet- and oxidised LDL (OxLDL)-induced lipid accumulation, decreased the mRNA expression of CD68 and CD36, and increased the mRNA expression of PPARα, LXRα, ABCA1 and ABCG1 in both hyperlipidaemic hamster-derived peritoneal and THP-1 macrophages. The administration of C. oil suppressed the mRNA expression of TNF-α, IL-1β, IL-6 and IFN-γ and increased the expression of TGF-β in peritoneal macrophages. In THP-1 macrophages, C. oil supplementation prevented OxLDL-induced production of TNF-α and IL-1β and increased the levels of TGF-β. The present study shows that C. oil attenuates arterial injury-induced accelerated atherosclerosis, inflammation and macrophage foam-cell formation.

Topics: Animals; Antigens, CD; Antigens, Differentiation, Myelomonocytic; Atherosclerosis; CD36 Antigens; Cholesterol, Dietary; Cricetinae; Curcuma; Diet, High-Fat; Foam Cells; Homeostasis; Inflammation; Interferon-gamma; Interleukin-10; Interleukin-1beta; Interleukin-6; Leukocyte Common Antigens; Lipoproteins, LDL; Macrophages, Peritoneal; Male; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Plant Extracts; Plant Oils; Plaque, Atherosclerotic; PPAR alpha; RNA, Messenger; Transforming Growth Factor beta; Tumor Necrosis Factor-alpha

After a ban on the use of antibiotics as growth promoters in farm animals in the European Union in 2006, an interest in alternative products with antibacterial or anti-inflammatory properties has increased. In this study, we therefore tested the effects of extracts from Curcuma longa and Scutellaria baicalensis used as feed additives against cecal inflammation induced by heat stress or Salmonella Enteritidis (S. Enteritidis) infection in chickens. Curcuma extract alone was not enough to decrease gut inflammation induced by heat stress. However, a mixture of Curcuma and Scutellaria extracts used as feed additives decreased gut inflammation induced by heat or S. Enteritidis, decreased S. Enteritidis counts in the cecum but was of no negative effect on BW or humoral immune response. Using next-generation sequencing of 16S rRNA we found out that supplementation of feed with the 2 plant extracts had no effect on microbiota diversity. However, if the plant extract supplementation was provided to the chickens infected with S. Enteritidis, Faecalibacterium, and Lactobacillus, both bacterial genera with known positive effects on gut health were positively selected. The supplementation of chicken feed with extracts from Curcuma and Scutelleria thus may be used in poultry production to effectively decrease gut inflammation and increase chicken performance.

Topics: Animal Feed; Animals; Anti-Bacterial Agents; Anti-Inflammatory Agents; Chickens; Curcuma; Diet; Dietary Supplements; Inflammation; Microbiota; Plant Extracts; Poultry Diseases; RNA, Ribosomal, 16S; Salmonella enteritidis; Salmonella Infections, Animal; Scutellaria

Curcumenol, a sesquiterpene isolated from Curcuma zedoaria is known to possess a variety of health and medicinal values which includes neuroprotection, anti-inflammatory, anti-tumor and hepatoprotective activities. The current study aim is to investigate the modulatory effects of curcumenol towards the lipopolysaccharides (LPS)-induced inflammation in BV-2 microglia. Curcumenol markedly decreased LPS-induced production of nitric oxide (NO), pro-inflammatory cytokines [(IL-6) and (TNF-α)] and pro-inflammatory proteins expression, iNOS and COX-2. Moreover, curcumenol inhibited NF-κB activation by suppressing the nuclear translocation of the NF-κB p65 subunit and blocking IκBα phosphorylation and degradation. Furthermore, an NF-κB inhibitor, ethyl 3,4-dihydroxycinnamate also known as caffeic acid ethyl ester (CAEE), attenuated LPS-stimulated iNOS and COX-2 expression, suggesting that NF-κB inhibition is a regulator in the expression of iNOS and COX-2 proteins. Further mechanistic study with an Akt inhibitor, triciribine hydrate (API-2), revealed that curcumenol acted through Akt-dependent NF-κB activation. Moreover, curcumenol inhibition on LPS-induced phosphorylation of p38 MAPK is confirmed by its inhibitor (SB 202190). These results indicate that curcumenol diminishes the proinflammatory mediators and the expression of the regulatory genes in LPS-stimulated BV-2 by inhibiting Akt-dependent NF-κB activation and downregulation of Akt and p38 MAPKs signaling.

Topics: Animals; Anti-Inflammatory Agents; Curcuma; Cytokines; Down-Regulation; Inflammation; Lipopolysaccharides; MAP Kinase Signaling System; Mice; Microglia; NF-kappa B; Nitric Oxide; Nitric Oxide Synthase Type II; Phosphorylation; Phytotherapy; Proto-Oncogene Proteins c-akt; Sesquiterpenes; Signal Transduction

During the periparturient phase, cows are typically in an inflammation-like condition, and it has been proposed that inflammation associated with the induction of stress of the endoplasmic reticulum (ER) in the liver contributes to the development of fatty liver syndrome and ketosis. In the present study, the hypothesis that supplementation of dairy cows with a plant product consisting of green tea (95%) and curcuma extract (5%) rich in polyphenols attenuates inflammation and ER stress in the liver during early lactation was investigated. Twenty-seven cows were assigned to two groups, either a control group (n=14) or a treatment group (n=13). Both groups of cows received a total mixed ration, and the ration of the treatment group was supplemented with 0.175 g of the plant product per kg dry matter from week 3 prepartum to week 9 postpartum. Dry matter intake and energy balance during week 2 to week 9 postpartum were not different between the two groups. However, cows supplemented with the plant product had a greater amount of energy-corrected milk during week 2 to week 9 postpartum and lower concentrations of triacylglycerols and cholesterol in the liver in week 1 and week 3 postpartum than cows of the control group (p<0.05). Cows supplemented with the plant product showed a trend towards a reduced mRNA concentration of haptoglobin (p<0.10), while relative mRNA concentrations of eight genes of the unfolded protein response considered in the liver were not different between the two groups of cows. Relative hepatic mRNA concentration of fibroblast growth factor, a stress hormone induced by various stress conditions, was reduced at week 1 and week 3 postpartum in cows supplemented with the plant product (p<0.05). Overall, the data of this study suggest that--although there were only minor effects on the occurrence of ER stress and inflammation--a supplementation of polyphenols might be useful to improve milk yield and prevent fatty liver syndrome in dairy cows.

Topics: Animal Feed; Animals; Cattle; Cattle Diseases; Curcuma; Diet; Dietary Supplements; Endoplasmic Reticulum Stress; Female; Fibroblast Growth Factors; Gene Expression Regulation; Inflammation; Lactation; Liver; Milk; Plant Extracts; Polyphenols; Tea; Unfolded Protein Response

Spinal cord injury (SCI) is a serious clinical situation without any effective therapy to date. Traumatic SCI triggers a complex pathological process including inflammatory response and glial scar formation. In this study, we demonstrated that curcumin, a natural product which functions as an anti-inflammatory agent, inhibited the activation of signal transducer and activator of transcription-3 and NF-kappa B in the injured spinal cord. Curcumin treatment greatly reduced the astrogliosis in SCI mice and significantly decreased the expression of IL-1β and NO, as well as the number of Iba1(+) inflammatory cells at the lesion site. Notably, more residual axons and neurons were protected and significantly improved functional recovery was observed in the curcumin-treated mice, compared to the mice without curcumin treatment. These findings indicate that curcumin promotes spinal cord repair through inhibiting glial scar formation and inflammation and suggests the therapeutic potential of curcumin for SCI.

Topics: Animals; Cicatrix; Curcumin; Female; Gliosis; Inflammation; Interleukin-1beta; Mice, Inbred BALB C; Neuroglia; Neurons; Neuroprotective Agents; NF-kappa B; Nitric Oxide; Spinal Cord; Spinal Cord Injuries; STAT3 Transcription Factor

Consuming curcumin may benefit health by modulating lipid metabolism and suppressing atherogenesis. Fatty acid binding proteins (FABP-4/aP2) and CD36 expression are key factors in lipid accumulation in macrophages and foam cell formation in atherogenesis. Our earlier observations suggest that curcumin's suppression of atherogenesis might be mediated through changes in aP2 and CD36 expression in macrophages. Thus, this study aimed to further elucidate the impact of increasing doses of curcumin on modulation of these molecular mediators on high fat diet-induced atherogenesis, inflammation, and steatohepatosis in Ldlr(-/-) mice.. Ldlr(-/-) mice were fed low fat (LF) or high fat (HF) diet supplemented with curcumin (500 HF + LC; 1000 HF + MC; 1500 HF + HC mg/kg diet) for 16 wks. Fecal samples were analyzed for total lipid content. Lipids accumulation in THP-1 cells and expression of aP2, CD36 and lipid accumulation in peritoneal macrophages were measured. Fatty streak lesions and expression of IL-6 and MCP-1 in descending aortas were quantified. Aortic root was stained for fatty and fibrotic deposits and for the expression of aP2 and VCAM-1. Total free fatty acids, insulin, glucose, triglycerides, and cholesterol as well as several inflammatory cytokines were measured in plasma. The liver's total lipids, cholesterol, triglycerides, and HDL content were measured, and the presence of fat droplets, peri-portal fibrosis and glycogen was examined histologically.. Curcumin dose-dependently reduced uptake of oxLDL in THP-1 cells. Curcumin also reduced body weight gain and body fat without affecting fat distribution. During early intervention, curcumin decreased fecal fat, but at later stages, it increased fat excretion. Curcumin at medium doses of 500-1000 mg/kg diet was effective at reducing fatty streak formation and suppressing aortic expression of IL-6 in the descending aorta and blood levels of several inflammatory cytokines, but at a higher dose (HF + HC, 1500 mg/kg diet), it had adverse effects on some of these parameters. This U-shape like trend was also present when aortic root sections were examined histologically. However, at a high dose, curcumin suppressed development of steatohepatosis, reduced fibrotic tissue, and preserved glycogen levels in liver.. Curcumin through a series of complex mechanisms, alleviated the adverse effects of high fat diet on weight gain, fatty liver development, dyslipidemia, expression of inflammatory cytokines and atherosclerosis in Ldlr(-/-) mouse model of human atherosclerosis. One of the mechanisms by which low dose curcumin modulates atherogenesis is through suppression of aP2 and CD36 expression in macrophages, which are the key players in atherogenesis. Overall, these effects of curcumin are dose-dependent; specifically, a medium dose of curcumin in HF diet appears to be more effective than a higher dose of curcumin.

Topics: Adipose Tissue; Animals; Atherosclerosis; Body Weight; CD36 Antigens; Cell Line; Cells, Cultured; Curcumin; Cytokines; Diet, High-Fat; Fatty Acid-Binding Proteins; Fatty Liver; Female; Humans; Inflammation; Lipid Metabolism; Lipoproteins, LDL; Liver; Macrophages; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Oxygen; Receptors, LDL; Triglycerides

The cellular and molecular mechanisms by which neuroinflammatory pathways respond to and propagate the reactive tissue response to intracortical microelectrodes remain active areas of research. We previously demonstrated that both the mechanical mismatch between rigid implants and the much softer brain tissue, as well as oxidative stress, contribute to the neurodegenerative reactive tissue response to intracortical implants. In this study, we utilize physiologically responsive, mechanically adaptive polymer implants based on poly(vinyl alcohol) (PVA), with the capability to also locally administer the antioxidant curcumin. The goal of this study is to investigate if the combination of two independently effective mechanisms - softening of the implant and antioxidant release - leads to synergistic effects in vivo. Over the first 4weeks of the implantation, curcumin-releasing, mechanically adaptive implants were associated with higher neuron survival and a more stable blood-brain barrier at the implant-tissue interface than the neat PVA controls. 12weeks post-implantation, the benefits of the curcumin release were lost, and both sets of compliant materials (with and without curcumin) had no statistically significant differences in neuronal density distribution profiles. Overall, however, the curcumin-releasing softening polymer implants cause minimal implant-mediated neuroinflammation, and embody the new concept of localized drug delivery from mechanically adaptive intracortical implants.

Topics: Animals; Antioxidants; Astrocytes; Biphenyl Compounds; Blood-Brain Barrier; Cell Count; Cellulose; Cerebral Cortex; Cicatrix; Curcumin; Glial Fibrillary Acidic Protein; HMGB1 Protein; Immunoglobulin G; Implants, Experimental; Inflammation; Macrophages; Male; Microglia; Nanoparticles; Neuraminidase; Neurons; Permeability; Picrates; Polyvinyl Alcohol; Rats; Urochordata; Wound Healing

Experimental autoimmune neuritis (EAN) is a helper T cell-mediated autoimmune demyelinating inflammatory disease of the peripheral nervous system that serves as an animal model for human Guillain-Barre syndrome. Curcumin, a naturally occurring polyphenolic phytochemical isolated from the medicinal plant Curcuma longa, has anti-inflammatory activities. Here we investigated the therapeutic effects and potential mechanisms of curcumin in EAN rats. Exogenous curcumin treatment (100 mg/kg/day) significantly delayed the onset of EAN neurological signs, ameliorated EAN neurological severity, and reduced body weight loss of EAN rats. In EAN sciatic nerves, curcumin treatment suppressed the inflammatory cell accumulation and the expression of interferon (IFN)-γ, tumor necrosis factor-α, interleukin (IL)-1β, and IL-17. Furthermore, curcumin treatment significantly decreased the percentage of CD4(+) T helper cells in EAN spleen and suppressed concanavalin A-induced lymphocyte proliferation in vitro. In addition, curcumin altered helper T cell differentiation by decreasing IFN-γ(+) CD4(+) Th1 cells in EAN lymph node and spleen. In summary, our data demonstrate that curcumin could effectively suppress EAN by attenuating inflammation, indicating that curcumin might be a candidate for treatment of autoimmune neuropathies.

Topics: Animals; CD4-Positive T-Lymphocytes; Cell Differentiation; Curcumin; Enzyme Inhibitors; Flow Cytometry; Inflammation; Lymphocyte Activation; Male; Neuritis, Autoimmune, Experimental; Rats; Rats, Inbred Lew; Real-Time Polymerase Chain Reaction; Sciatic Nerve

Among Spinal Cord Injury (SCI) intervention the administration of high-dose high-potency steroidal drugs such as methylprednisolone or dexamethasone is used to reduce the inflammation associated with primary injury and prevention of the subsequent secondary injury. The administration of steroids has several side-effects that jeopardize their use and therefore safer chemical neuro-entities are required. Natural compounds such as curcumin (anti-oxidant) and quercetin (anti-inflammatory) have been investigated as alternative neuroactive, but are not as potent as the steroids. Hence, they are required in very high doses which may lead to significant toxicity causing an increase in cellular levels of reactive oxygen species, active iron chelation, inhibiting the activity of the cytochrome P450 enzymes such as glutathione-S-transferase and UDP-glucuronosyltransferase. A reduction in the dose of these neuroactives is possible with the administration of a 'chemically-variant' permutation with additive or synergistic therapeutic benefits. Therefore, we hypothesize that curcumin and quercetin, both natural polyphenolic flavonoids, can "additively and synergistically" improve the physiological outcome after traumatic SCI when used in combination and termed 'Cur(Que)min' - thereby decreasing the dose levels and hence reducing the inherent high dose-cytotoxicity of the individual neuroactives. This hypothesis provides the first-account of a curcumin-quercetin combination for SCI intervention theorizing the possible biomolecular-mechanism that may provide the scientific community with a novel neuroprotective and neurotherapeutic treatment option for SCI.

Topics: Antioxidants; Curcumin; Glutathione Transferase; Humans; Inflammation; Models, Theoretical; Neuroprotective Agents; Phenol; Quercetin; Reactive Oxygen Species; Spinal Cord Injuries; Steroids

The objective was to develop a stable, reproducible and patient non-infringing novel transdermal drug delivery system "nano-carrier transdermal gel" (NCTG) in combination of partial dose replacement of diclofenac diethylamine (DDEA) by curcumin (CRM). The drug content of gel was 99.30 and 97.57% for DDEA and CRM. Plasma samples were analyzed by liquid chromatography with triple-quadrupole tandem mass spectrometer (LC-MS/MS). Data were integrated with Analyst™ and analyzed by WinNonlin; stability parameters were analyzed using Tukey-Kramer multiple comparison test. Its average skin irritation scored 0.49 concluded to be non-irritant, safe for human use and in vivo studies revealed significantly greater extent of absorption and highly significant inhibition (%) of carrageenan induced paw edema. The results also demonstrated that encapsulation of drugs in nano-carrier increases its biological activity due to superior skin penetration potential. Hence, a novel once day transdermal gel of nano-carrier (nano-transfersomes; deformable vesicular) is achieved, to increase systemic availability, subsequent reduction in dose and toxicity of DDEA was developed for the treatment of inflammation.

Topics: Acrylates; Administration, Cutaneous; Animals; Anti-Inflammatory Agents; Biological Availability; Carrageenan; Chemistry, Pharmaceutical; Chromatography, Liquid; Curcumin; Diclofenac; Disease Models, Animal; Drug Administration Schedule; Drug Carriers; Drug Combinations; Drug Stability; Gels; Inflammation; Male; Nanoparticles; Nanotechnology; Rats, Wistar; Skin; Skin Irritancy Tests; Tandem Mass Spectrometry; Technology, Pharmaceutical

Decreasing organ quality is prompting research toward new methods to alleviate ischemia reperfusion injury (IRI). Oxidative stress and nuclear factor kappa beta (NF-κB) activation are well-described elements of IRI. We added cyclodextrin-complexed curcumin (CDC), a potent antioxidant and NF-κB inhibitor, to University of Wisconsin (UW) solution (Belzer's Solution, Viaspan), one of the most effective clinically approved preservative solutions. The effects of CDC were evaluated on pig endothelial cells and in an autologous donation after circulatory death (DCD) kidney transplantation model in large white pigs. CDC allowed rapid and lasting uptake of curcumin into cells. In vitro, CDC decreased mitochondrial loss of function, improved viability and lowered endothelial activation. In vivo, CDC improved function recovery, lowered histological injury and doubled animal survival (83.3% vs. 41.7%). At 3 months, immunohistochemical staining for epithelial-to-mesenchymal transition (EMT) and fibrosis markers was intense in UW grafts while it remained limited in the UW + CDC group. Transcriptional analysis showed that CDC treatment protected against up-regulation of several pathophysiological pathways leading to inflammation, EMT and fibrosis. Thus, use of CDC in a preclinical transplantation model with stringent IRI rescued kidney grafts from an unfavorable prognosis. As curcumin has proved well tolerated and nontoxic, this strategy shows promise for translation to the clinic.

Topics: Adenosine; Allopurinol; Animals; Anti-Inflammatory Agents, Non-Steroidal; Blotting, Western; Cells, Cultured; Chemistry, Pharmaceutical; Curcumin; Cyclodextrins; Disease Models, Animal; Fibrosis; Flow Cytometry; Glutathione; Graft Rejection; Humans; Inflammation; Insulin; Kidney Transplantation; Kidney Tubules; Male; Organ Preservation Solutions; Oxidative Stress; Prostate; Raffinose; Real-Time Polymerase Chain Reaction; Reperfusion Injury; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Swine

It is known that inducible nitric oxide synthase (iNOS)/nitric oxide (NO) plays an integral role during intestinal inflammation, an important factor for colon cancer development. Natural compounds from Curcuma longa L. (Zingiberaceae) have long been a potential source of bioactive materials with various beneficial biological functions. Among them, a major active curcuminoid, demethoxycurcumin (DMC) has been shown to possess anti-inflammatory properties in lipopolysaccharide (LPS)-activated macrophages or microglia cells. However, the role of DMC on iNOS expression and NO production in an in vitro inflamed human intestinal mucosa model has not yet been elucidated. This study concerned inhibitory effects on iNOS expression and NO production of DMC in inflamed human intestinal Caco-2 cells. An in vitro model was generated and inhibitory effects on NO production of DMC at 65 μM for 24-96 h were assessed by monitoring nitrite levels. Expression of iNOS mRNA and protein was also investigated. DMC significantly decreased NO secretion by 35-41% in our inflamed cell model. Decrease in NO production by DMC was concomitant with down-regulation of iNOS at mRNA and protein levels compared to proinflammatory cytokine cocktail and LPS-treated controls. Mechanism of action of DMC may be partly due to its potent inhibition of the iNOS pathway. Our findings suggest that DMC may have potential as a therapeutic agent against inflammation-related diseases, especially in the gut.

Topics: Anti-Inflammatory Agents; Caco-2 Cells; Cell Line, Tumor; Curcuma; Curcumin; Diarylheptanoids; Humans; Inflammation; Intestinal Mucosa; Lipopolysaccharides; Nitric Oxide; Nitric Oxide Synthase Type II; Plant Preparations; RNA, Messenger

Insufficient clearance by microglial cells, prevalent in several neurological conditions and diseases, is intricately intertwined with MFG-E8 expression and inflammatory responses. Electromagnetic field (EMF) exposure can elicit the pro-inflammatory activation and may also trigger an alteration of the clearance function in microglial cells. Curcumin has important roles in the anti-inflammatory and phagocytic process. Here, we evaluated the ability of curcumin to ameliorate the phagocytic ability of EMF-exposed microglial cells (N9 cells) and documented relative pathways.. N9 cells were pretreated with or without recombinant murine MFG-E8 (rmMFG-E8), curcumin and an antibody of toll-like receptor 4 (anti-TLR4), and subsequently treated with EMF or a sham exposure. Their phagocytic ability was evaluated using phosphatidylserine-containing fluorescent bioparticles. The pro-inflammatory activation of microglia was assessed via CD11b immunoreactivity and the production of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1β (IL-1β) and nitric oxide (NO) via the enzyme-linked immunosorbent assay or the Griess test. We evaluated the ability of curcumin to ameliorate the phagocytic ability of EMF-exposed N9 cells, including checking the expression of MFG-E8, αvβ3 integrin, TLR4, nuclear factor-κB (NF-κB) and signal transducer and activator of transcription 3 (STAT3) using Western blotting.. EMF exposure dramatically enhanced the expression of CD11b and depressed the phagocytic ability of N9 cells. rmMFG-E8 could clearly ameliorate the phagocytic ability of N9 cells after EMF exposure. We also found that EMF exposure significantly increased the secretion of pro-inflammatory cytokines (TNF-α, IL-6 and IL-1β) and the production of NO; however, these increases were efficiently chilled by the addition of curcumin to the culture medium. This reduction led to the amelioration of the phagocytic ability of EMF-exposed N9 cells. Western blot analysis revealed that curcumin and naloxone restored the expression of MFG-E8 but had no effect on TLR4 and cytosolic STAT3. Moreover, curcumin significantly reduced the expression of NF-κB p65 in nuclei and phospho-STAT3 (p-STAT3) in cytosols and nuclei.. This study indicates that curcumin ameliorates the depressed MFG-E8 expression and the attenuated phagocytic ability of EMF-exposed N9 cells, which is attributable to the inhibition of the pro-inflammatory response through the NF-κB and STAT3 pathways.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; CD11b Antigen; Cell Line, Transformed; Curcumin; Cytokines; Dose-Response Relationship, Radiation; Down-Regulation; Electromagnetic Fields; Flow Cytometry; Inflammation; Mice; Microglia; NF-kappa B; Nitric Oxide; Phagocytes; Phagocytosis; STAT3 Transcription Factor; Time Factors

Much evidence demonstrates that microglia mediated neuroinflammation is an important contributor to the inflammatory injury in intracerebral hemorrhage (ICH). Therefore, the compounds that can inhibit neuroinflammation are greatly needed. In the current study, we examined whether curcumin, present in a Chinese medicinal plant, could prevent ICH induced microglia activation and confer protection against neurotoxicity. The cytokines of microglia were measured by ELISA, p38MAPK/PKC and NF-κB were measured by Western blot and EMSA. Microglial toxicity was assessed using MTT and FACS assays. And neurological function was evaluated by animal behavioristics. We found that curcumin prevented ICH-induced inflammatory molecules through NF-κB activation via the p38MAPK/PKC pathway in vitro. In addition, curcumin protected hippocampal HT22 cells from indirect toxicity mediated by ICH-treated microglia cells. Further, curcumin also attenuated ICH-induced neurological deficit and cerebral water content in vivo. Together, our findings suggest that curcumin could suppress ICH induced inflammatory injury and represent a novel herbal sources for ICH therapeutical strategy.

Topics: Animals; Apoptosis; Cell Line; Cell Movement; Cerebral Hemorrhage; Curcumin; Cytokines; Disease Models, Animal; Hippocampus; Inflammation; Inflammation Mediators; Male; Mice; Microglia; Neuroprotective Agents; NF-kappa B; p38 Mitogen-Activated Protein Kinases; Protein Kinase C; Signal Transduction

Curcumin, a natural product derived from the plant Curcuma longa, has been found to have anti-inflammatory, antineoplastic and antifibrosis effects. It has been reported that curcumin attenuates allergic airway inflammation in mice through inhibiting NF-κB and its downstream transcription factor GATA3. It also has been proved the antineoplastic effect of curcumin through down-regulating Notch1 receptor and its downstream nuclear transcription factor NF-κB levels. In this study, we aimed to investigate the anti-inflammatory effect of curcumin on acute allergic asthma and its underlying mechanisms. 36 male BALB/c mice were randomly divided into four groups (normal, asthma, asthma+budesonide and asthma+curcumin groups). BALF (bronchoalveolar lavage fluid) and lung tissues were analyzed for airway inflammation and the expression of Notch1, Notch2, Notch3, Notch4 and the downstream transcription factor GATA3. Our findings showed that the levels of Notch1 and Notch2 receptors were up-regulated in asthma group, accompanied by the increased expression of GATA3. But the expression of Notch2 receptor was lower than Notch1 receptor. Curcumin pretreatment improved the airway inflammatory cells infiltration and reversed the increasing levels of Notch1/2 receptors and GATA3. Notch3 receptor was not expressed in all of the four groups. Notch4 receptor protein and mRNA expression level in the four groups had no significant differences. The results of the present study suggested that Notch1 and Notch2 receptor, major Notch1 receptor, played an important role in the development of allergic airway inflammation and the inhibition of Notch1-GATA3 signaling pathway by curcumin can prevent the development and deterioration of the allergic airway inflammation. This may be a possible therapeutic option of allergic asthma.

Topics: Animals; Anti-Inflammatory Agents; Asthma; Curcuma; Curcumin; GATA3 Transcription Factor; Inflammation; Male; Mice; Mice, Inbred BALB C; Random Allocation; Receptor, Notch1; Signal Transduction

Resveratrol and curcumin are natural antioxidants found in the human diet that have been used in the prevention and treatment of different diseases associated with oxidative stress. Aiming to improve the antioxidant effects of resveratrol and curcumin, lipid-core nanocapsules containing the combination of both polyphenols were developed. Physicochemical characteristics were evaluated and compared to the formulations containing each polyphenol individually. Co-encapsulation did not influence nanotechnological characteristics, and all formulations presented mean diameter around 200 nm, low polydispersity index, and encapsulation efficiency close to 100%. Nanoencapsulation increases the photostability of resveratrol and curcumin, and co-encapsulation improves resveratrol photostability. The in vitro antioxidant activity of polyphenols against HO radicals was enhanced by nanoencapsulation, and a better effect was observed after their co-nanoencapsulation. Also, nanocapsules exhibited controlled release profile, for both polyphenols. The results showed that the strategy to co-encapsulate resveratrol and curcumin is a promising approach to improve the performance of medicines used to prevent and treat diseases associated with oxidative stress.

Topics: Antioxidants; Chromatography, High Pressure Liquid; Curcumin; Drug Delivery Systems; Free Radicals; Humans; Hydrogen-Ion Concentration; Inflammation; Lipids; Microscopy, Electron, Transmission; Nanocapsules; Nanoparticles; Nanotechnology; Oxidative Stress; Particle Size; Polyphenols; Resveratrol; Stilbenes

Hyperglycemia-induced inflammation and apoptosis have important roles in the pathogenesis of diabetic cardiomyopathy. We recently found that a novel curcumin derivative, C66, is able to reduce the high glucose (HG)-induced inflammatory response. This study was designed to investigate the protective effects on diabetic cardiomyopathy and its underlying mechanisms. Pretreatment with C66 significantly reduced HG-induced overexpression of inflammatory cytokines via inactivation of nuclear factor-κB in both H9c2 cells and neonatal cardiomyocytes. Furthermore, we showed that the inhibition of Jun NH2-terminal kinase (JNK) phosphorylation contributed to the protection of C66 from inflammation and cell apoptosis, which was validated by the use of SP600125 and dominant-negative JNK. The molecular docking and kinase activity assay confirmed direct binding of C66 to and inhibition of JNK. In mice with type 1 diabetes, the administration of C66 or SP600125 at 5 mg/kg significantly decreased the levels of plasma and cardiac tumor necrosis factor-α, accompanied by decreasing cardiac apoptosis, and, finally, improved histological abnormalities, fibrosis, and cardiac dysfunction without affecting hyperglycemia. Thus, this work demonstrated the therapeutic potential of the JNK-targeting compound C66 for the treatment of diabetic cardiomyopathy. Importantly, we indicated a critical role of JNK in diabetic heart injury, and suggested that JNK inhibition may be a feasible strategy for treating diabetic cardiomyopathy.

Topics: Animals; Apoptosis; Curcumin; Diabetic Cardiomyopathies; Glucose; Inflammation; JNK Mitogen-Activated Protein Kinases; Male; Mice; Mice, Inbred C57BL; Myocytes, Cardiac; NF-kappa B; Phosphorylation

Curcumin has been reported to possess multiple bioactivities, such as antioxidant, anticancer, and anti-inflammatory properties, however the clinical application of curcumin has been significantly limited by its instability and poor metabolism. Modification of curcumin has led to discovery and development of lots of novel therapeutic candidates. In recent years acute and chronic inflammation has been the focus of numerous studies in various diseases. Here, we synthesized a series of asymmetrical curcumin analogs with high in vitro chemical stability, and their anti-inflammatory activity was evaluated in LPS-stimulated macrophages. According to the bio-screening results and QSAR analysis, these analogs exhibited potent activities against LPS-induced TNF-α and IL-6 release. Among the analogs of the potent anti-inflammatory activity, compounds 3b8 and 3b9 exhibited significant protection and possess enhanced anti-inflammatory activity thereby attenuated the LPS-induced septic death in mice.

Topics: Animals; Anti-Inflammatory Agents; Cell Line, Tumor; Curcumin; Humans; Inflammation; Interleukin-6; Lipopolysaccharides; Macrophages; Male; Mice; Quantitative Structure-Activity Relationship; Structure-Activity Relationship; Tumor Necrosis Factor-alpha

This study investigated the protective effects of curcumin on tetrachloro-p-benzoquinone (TCBQ)-induced hepatotoxicity in mice. TCBQ-treatment causes significant liver injury (the elevation of serum AST and ALT activities, histopathological changes in liver section including centrilobular necrosis and inflammatory cells), oxidative stress (the elevation of TBAR level and the inhibition of SOD and catalase activities) and inflammation (up-regulation of iNOS, COX-2, IL-1β, IL-6, TNF-α and NF-κB). However, these changes were alleviated upon pretreatment with curcumin. Interestingly, TCBQ has no effect on caspase family genes or B-cell lymphoma 2 (Bcl-2)/Bcl-2 associated X (Bax) protein expressions, which implied that TCBQ-induced hepatotoxicity is independent of apoptosis. Moreover, curcumin was shown to induce phase II detoxifying/antioxidant enzymes HO-1 and NQO1 through the activation of nuclear factor erythroid-derived 2-like 2 (Nrf2). In summary, the protective mechanisms of curcumin against TCBQ-induced hepatoxicity may be related to the attenuation of oxidative stress, along with the inhibition of inflammatory response via the activation of Nrf2 signaling.

Topics: Alanine Transaminase; Animals; Apoptosis; Aspartate Aminotransferases; Benzoquinones; Caspases; Curcumin; Hydrocarbons, Chlorinated; Inflammation; Interleukin-6; Liver; Male; Mice; NF-E2-Related Factor 2; NF-kappa B; Nitric Oxide Synthase Type II; Oxidative Stress; Proto-Oncogene Proteins c-bcl-2

Topics: Animals; Apoptosis; Curcumin; Diabetic Cardiomyopathies; Inflammation; JNK Mitogen-Activated Protein Kinases; Male; Myocytes, Cardiac

Curcumin and capsaicin are dietary xenobiotics with well-documented anti-inflammatory properties. Previously, the beneficial effect of these spice principles in lowering chronic inflammation was demonstrated using a rat experimental model for arthritis. The extent of lowering of arthritic index by the spice principles was associated with a significant shift in macrophage function favoring the reduction of pro-inflammatory molecules such as reactive oxygen species and production and release of anti-inflammatory metabolites of arachidonic acid. Beyond the cellular effects on macrophage function, oral administration of curcumin and capsaicin caused alterations in serum protein profiles of rats injected with adjuvant to develop arthritis. Specifically, a 72 kDa acidic glycoprotein, GpA72, which was elevated in pre-arthritic rats, was significantly lowered by feeding either curcumin or capsaicin to the rats. Employing the tandem mass spectrometric approach for direct sequencing of peptides, here we report the identification of GpA72 as T-kininogen I also known as Thiostatin. Since T-kininogen I is an early acute-phase protein, we additionally tested the efficiency of curcumin and capsaicin to mediate the inflammatory response in an acute phase model. The results demonstrate that curcumin and capsaicin lower the acute-phase inflammatory response, the molecular mechanism for which is, in part, mediated by pathways associated with the lowering of T-kininogen I.

Topics: Acute-Phase Proteins; Animals; Arachidonic Acid; Capsaicin; Curcumin; Diet; Disease Models, Animal; Glycoproteins; Inflammation; Kininogens; Male; Mass Spectrometry; Rats; Rats, Wistar; Reactive Oxygen Species

The Mycobacterium tuberculosis 19-kDa lipoprotein (P19) is both cell wall-associated and secreted and is a candidate virulence factor that could cause the apoptosis of human macrophages infected with M. tuberculosis. P19 induces TLR2 activation, resulting in the upregulation of death receptors and ligands, followed by a death-receptor signaling cascade. The mechanisms by which P19 induces macrophage apoptosis are not fully characterized. Curcumin, a natural polyphenol, exhibits a variety of pharmacological effects such as antioxidant, anti-inflammatory and antitumor properties. In the present study, we investigated the effect of curcumin on P19-induced apoptosis in human macrophage cells and the underlying mechanisms. The results showed that both P19 and curcumin inhibit the growth of macrophages in a dose- and time-dependent manner. A low dose of curcumin (10 or 20 µM) attenuated both the macrophage cell growth inhibition and the increase in the expression of IL-6 and TNF-α induced by P19. Curcumin also decreased the phosphorylation of JNK and p38 that were induced by P19. However, JNK but not p38 inhibitors reversed the effect of P19 on the growth inhibition of macrophages. These data suggest that curcumin may protect macrophages from P19-induced cell apoptosis via a TLR2-mediated JNK-dependent pathway.

Topics: Apoptosis; Bacterial Proteins; Cell Line; Curcumin; Humans; Inflammation; Interleukin-6; Lipoproteins; Macrophages; MAP Kinase Signaling System; Mycobacterium tuberculosis; p38 Mitogen-Activated Protein Kinases; Phosphorylation; Receptors, Death Domain; Signal Transduction; Toll-Like Receptor 2; Tuberculosis; Tumor Necrosis Factor-alpha

Inflammatory bowel disease (IBD) is a chronic relapsing disease. Genetic predisposition to the disease reduces an individual's capacity to respond appropriately to environmental challenges in the intestine leading to inappropriate inflammation. IBD patients often modify their diet to mitigate or reduce the severity of inflammation. Turmeric (Curcuma longa L., Zingiberaceae) has historically been used in Chinese, Hindu, and Ayurvedic medicine over several centuries to treat inflammatory disorders. To understand how turmeric may influence the consequences of a genetic predisposition to inappropriate inflammation, we used HEK293 cells to examine the in vitro capacity of turmeric extract and fractions to affect the functionality of two gene variants, solute carrier protein 22 A4 (SLC22A4, rs1050152) and interleukin-10 (IL-10, rs1800896) associated with IBD. We found that a turmeric extract and several chromatographically separated fractions beneficially affected the variants of SLC22A4 and IL-10 associated with IBD, by reducing inappropriate epithelial cell transport (SLC22A4, 503F) and increasing anti-inflammatory cytokine gene promoter activity (IL-10, -1082A). The effect of turmeric on the IL-10 variant was strongly associated with the curcumin content of the extract and its fractions.

Topics: Curcuma; Curcumin; Epithelial Cells; HEK293 Cells; Humans; In Vitro Techniques; Inflammation; Inflammatory Bowel Diseases; Interleukin-10; Organic Cation Transport Proteins; Plant Extracts; Symporters

Flavonoids are group of compounds that have been shown to possess potent anti-inflammatory effects in both cellular and animal models of inflammation. In the current study, the single and combined effects of the two flavonoids, curcumin and quercetin, against carrageenan-induced acute inflammation in rats were evaluated with emphasis on the role of oxidative stress, anti-inflammatory enzyme, heme oxygenase-1 (HO-1) and proinflammatory cytokine, tumor necrosis factor-alpha (TNF-α). Curcumin (50 mg/kg), quercetin (50 mg/kg) and a combination of both were orally administered for 14 days before carrageenan injection in rats and compared with the reference nonsteroidal anti-inflammatory drug, indomethacin (10 mg/kg). The percentage increase in paw thickness was calculated. Frozen hind paws were used for the estimation of lipid peroxides (malondialdehyde, MDA), nitric oxide (NO), reduced glutathione (GSH), TNF-α level and HO-1 messenger RNA (mRNA) expression. Formalin-fixed hind paws were used for histopathological examination. Results showed that both curcumin and quercetin caused reduction in carrageenin-induced edema and lymphocytes infiltration along with the decrease is being even higher in case of their combination. Additionally, both flavonoids reduced MDA and NO formation, and restored GSH contents in the paw. Furthermore, both flavonoids increased HO-1 mRNA expression and decreased the elevated TNF-α level. Results showed that both flavonoids moderately lowered inflammation, while their combination was more effective. Accordingly, this study suggests that the reduction in oxidative stress and modulation of HO-1 mRNA expression and TNF-α release by curcumin and quercetin may contribute to the synergistic anti-inflammatory effects of these two flavonoids upon combination.

Topics: Animals; Anti-Inflammatory Agents; Anti-Inflammatory Agents, Non-Steroidal; Curcumin; Drug Interactions; Heme Oxygenase (Decyclizing); Indomethacin; Inflammation; Male; Oxidative Stress; Quercetin; Rats; Tumor Necrosis Factor-alpha

Endothelial cells initiated inflammation persisting in postmyocardial infarction needs to be controlled and moderated for avoiding fatal complications. Curcuma oil (C.oil, Herbal Medicament), a standardized hexane soluble fraction of Curcuma longa has possessed neuroprotective effect. However, its effect on myocardial ischemia/reperfusion (MI/RP) and endothelial cells remains incompletely defined. Here, using in vivo rat MI/RP injury model and in vitro cellular approaches using EA.hy926 endothelial cells, enzyme-linked immunosorbent assay, real-time polymerase chain reaction, and myograph, we provide evidence that with effective regimen and preconditioning of rats with C.oil (250 mg/kg, PO), before and after MI/RP surgery protects rats from MI/RP-induced injury. C.oil treatment reduces left ventricular ischemic area and endothelial cell-induced inflammation, specifically in the ischemic region (*P < 0.0001) and improved endothelial function by reducing the expression of proinflammatory genes and adhesion factors on endothelial cells both in vitro and in vivo. Furthermore, mechanistic studies have revealed that C.oil reduced the expression of adhesion factors like E-selectin (#P = 0.0016) and ICAM-1 ($P = 0.0069) in initiating endothelial cells-induced inflammation. In line to the real-time polymerase chain reaction expression data, C.oil reduced the adhesion of inflammatory cells to endothelial cells as assessed by the interaction of THP-1 monocytes with the endothelial cells using flow-based adhesion and under inflammatory conditions. These studies provide evidence that salutary effect of C.oil on MI/RP could be achieved with pretreatment and posttreatment of rats, C.oil reduced MI/RP-induced injury by reducing the endothelial cell-mediated inflammation, specifically in the ischemic zone of MI/RP rat heart.

Topics: Animals; Cell Line; Curcuma; Disease Models, Animal; E-Selectin; Endothelial Cells; Enzyme-Linked Immunosorbent Assay; Humans; Inflammation; Male; Monocytes; Myocardial Reperfusion Injury; Oils, Volatile; Rats; Rats, Wistar; Real-Time Polymerase Chain Reaction

Acute Respiratory Distress Syndrome (ARDS) is a clinical syndrome characterized by diffuse alveolar damage usually secondary to an intense host inflammatory response of the lung to a pulmonary or extrapulmonary infectious or non-infectious insult often leading to the development of intra-alveolar and interstitial fibrosis. Curcumin, the principal curcumoid of the popular Indian spice turmeric, has been demonstrated as an anti-oxidant and anti-inflammatory agent in a broad spectrum of diseases. Using our well-established model of reovirus 1/L-induced acute viral pneumonia, which displays many of the characteristics of the human ALI/ARDS, we evaluated the anti-inflammatory and anti-fibrotic effects of curcumin. Female CBA/J mice were treated with curcumin (50 mg/kg) 5 days prior to intranasal inoculation with 10(7)pfu reovirus 1/L and daily, thereafter. Mice were evaluated for key features associated with ALI/ARDS. Administration of curcumin significantly modulated inflammation and fibrosis, as revealed by histological and biochemical analysis. The expression of IL-6, IL-10, IFNγ, and MCP-1, key chemokines/cytokines implicated in the development of ALI/ARDS, from both the inflammatory infiltrate and whole lung tissue were modulated by curcumin potentially through a reduction in the phosphorylated form of NFκB p65. While the expression of TGFß1 was not modulated by curcumin, TGFß Receptor II, which is required for TGFß signaling, was significantly reduced. In addition, curcumin also significantly inhibited the expression of α-smooth muscle actin and Tenascin-C, key markers of myofibroblast activation. This data strongly supports a role for curcumin in modulating the pathogenesis of viral-induced ALI/ARDS in a pre-clinical model potentially manifested through the alteration of inflammation and myofibroblast differentiation.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Chemokine CCL2; Curcumin; Disease Models, Animal; Female; Fibrosis; Gene Expression; Humans; Inflammation; Injections, Intraperitoneal; Interferon-gamma; Interleukin-10; Interleukin-6; Mice; Mice, Inbred CBA; Orthoreovirus, Mammalian; Protein Serine-Threonine Kinases; Receptor, Transforming Growth Factor-beta Type II; Receptors, Transforming Growth Factor beta; Reoviridae Infections; Respiratory Distress Syndrome; Signal Transduction; Tenascin; Transcription Factor RelA; Transforming Growth Factor beta1

Curcumin (CUR) has deserved extensive research due to its anti-inflammatory properties, of interest in human diseases including cancer. However, pleiotropic even paradoxical responses of tumor cells have been reported, and the mechanisms of action of CUR remain uncompletely elucidated.. (1)H-NMR spectroscopy-based metabolomics was applied to get novel insight into responses of MCF7 and MDA-MB-231 breast cancer cells to CUR alone, and MCF7 cells to CUR in cotreatment with docetaxel (DTX). In both cell types, a major target of CUR was glutathione metabolism. Total glutathione (GSx) increased at low dose CUR (≤ 10 mg.l(-1)-28 µM-) (up to +121% in MCF7 cells, P<0.01, and +138% in MDA-MB-231 cells, P<0.01), but decreased at high dose (≥ 25 mg.l(-1) -70 µM-) (-49%, in MCF7 cells, P<0.02, and -56% in MDA-MB-231 cells, P<0.025). At high dose, in both cell types, GSx-related metabolites decreased, including homocystein, creatine and taurine (-60 to -80%, all, P<0.05). Together with glutathione-S-transferase actvity, data established that GSx biosynthesis was upregulated at low dose, and GSx consumption activated at high dose. Another major target, in both cell types, was lipid metabolism involving, at high doses, accumulation of polyunsaturated and total free fatty acids (between ×4.5 and ×11, P<0.025), and decrease of glycerophospho-ethanolamine and -choline (about -60%, P<0.025). Multivariate statistical analyses showed a metabolic transition, even a biphasic behavior of some metabolites including GSx, between low and high doses. In addition, CUR at 10 mg.l(-1) in cotreatment with DTX induced modifications in glutathione metabolism, lipid metabolism, and glucose utilization. Some of these changes were biphasic depending on the duration of exposure to CUR.. Metabolomics reveals major metabolic targets of CUR in breast cancer cells, and biphasic responses that challenge the widely accepted beneficial effects of the phytochemical.

Topics: Antineoplastic Agents; Breast Neoplasms; Cell Line, Tumor; Comet Assay; Curcumin; Docetaxel; Female; Glutathione; Glutathione Transferase; Humans; Inflammation; Magnetic Resonance Spectroscopy; MCF-7 Cells; Metabolomics; Multivariate Analysis; Oxidative Stress; Taxoids; Treatment Outcome

A tenet of contemporary obstetrics is that a significant proportion of preterm births involve bacterial infection. Bacterial endotoxin induces pro-inflammatory cytokines, prostaglandins and proteases via the pro-inflammatory pathway nuclear factor-κB (NF-κB), which plays a key role in initiating uterine contractions and rupture of foetal membranes. In non-gestational tissues, the phytophenols curcumin, naringenin and apigenin exert anti-inflammatory properties via inhibition of NF-κB. The aim of this study was to determine whether these treatments regulate pro-inflammatory and pro-labour mediators in human gestational tissues. Placenta, foetal membranes and myometrium were treated with curcumin, naringenin and apigenin in the presence of lipopolysaccharide (LPS) or interleukin (IL)-1β. In placenta and foetal membranes, all treatments significantly reduced LPS-stimulated release and gene expression of pro-inflammatory cytokines IL-6 and IL-8; placenta decreased cyclooxygenase (COX-2) mRNA expression, subsequent release of prostaglandins PGE2 and PGF2α and expression and activity of matrix-degrading enzyme matrix metalloproteinase (MMP)-9. In myometrial cells, all treatments attenuated IL-1β-induced COX-2 expression, release of PGE2 and PGF2α and expression and activity of MMP-9. Although naringenin significantly attenuated IL-1β-induced IL-6 and IL-8 mRNA expression and release, there was no effect of curcumin and apigenin. LPS-stimulated release of 8-isoprostane, a marker of oxidative stress, was attenuated by all treatments. NF-κB p65 DNA-binding activity was also decreased using these treatments. In conclusion, curcumin, naringenin and apigenin exert anti-inflammatory properties in human gestational tissues by inhibiting the transcriptional activity of NF-κB. Further studies should be undertaken to define a possible implication of these natural spices in the management of preterm labour and delivery.

Topics: Apigenin; Cells, Cultured; Curcumin; Cyclooxygenase 2; Dietary Supplements; Extraembryonic Membranes; Female; Flavanones; Humans; In Vitro Techniques; Inflammation; Interleukin-6; Interleukin-8; Myometrium; Placenta; Pregnancy; Premature Birth; Reverse Transcriptase Polymerase Chain Reaction; Transcription Factor RelA

The present study aimed to determine the protective effects and the underlying mechanisms of curcumin on ovalbumin (OVA)-induced allergic inflammation in a mouse model of allergic asthma. Asthma mice model was established by ovalbumin. A total of 60 mice were randomly assigned to six experimental groups: control, model, dexamethasone (2 mg/kg), and curcumin (50 mg/kg, 100 mg/kg, 200 mg/kg). Airway resistance (Raw) was measured by the forced oscillation technique, differential cell count in BAL fluid (BALF) was measured by Wright-Giemsa staining, histological assessment was measured by hematoxylin and eosin (HE) staining, BALF levels of Treg/Th17 cytokines were measured by enzyme-linked immunosorbent assay, Treg cells and Th17 cells were evaluated by flow cytometry (FCM). Our study demonstrated that curcumin inhibited OVA-induced increases in eosinophil count; interleukin (IL)-17A level were recovered in bronchoalveolar lavage fluid increased IL-10 level in bronchoalveolar lavage fluid. Histological studies demonstrated that curcumin substantially inhibited OVA-induced eosinophilia in lung tissue. Flow cytometry (FCM) studies demonstrated that curcumin remarkably inhibited Th17 cells and significantly increased Treg cells. The results in vivo show ovalbumin-induced significantly broke Treg/Th17 balance; curcumin treatments markedly attenuated the inflammatory in asthma model by regulating Treg/Th17 balance. Our findings support the possible use of curcumin as a therapeutic drug for patients with allergic asthma.

Topics: Airway Resistance; Animals; Anti-Inflammatory Agents; Asthma; Bronchial Hyperreactivity; Bronchoalveolar Lavage Fluid; CD4 Antigens; Curcuma; Curcumin; Eosinophilia; Eosinophils; Female; Inflammation; Interleukin-10; Interleukin-17; Interleukin-2 Receptor alpha Subunit; Lung; Mice; Mice, Inbred BALB C; Ovalbumin; Phytotherapy; Plant Extracts; T-Lymphocytes, Regulatory; Th17 Cells

The present study evaluated the effects of curcumin on epithelial cell apoptosis, the immunoreactivity of the phospho-c-Jun N-terminal kinase (JNK) and phospho-p38 mitogen-activated protein kinases (MAPKs) in inflamed colon mucosa, and oxidative stress in a rat model of ulcerative colitis induced by acetic acid. Rats were randomly divided into three groups: control, acetic acid, and acetic acid+curcumin. Curcumin (100 mg/kg per day, intragastrically) was administered 10 days before the induction of colitis and was continued for two additional days. Acetic acid-induced colitis caused a significant increase in the macroscopic and microscopic tissue ranking scores as well as an elevation in colonic myeloperoxidase (MPO) activity, malondialdehyde (MDA) levels, and the number of apoptotic epithelial cells in colon tissue compared to controls. In the rat colon, immunoreactivity of phospho-p38 MAPK was increased, whereas the phospho-JNK activity was decreased following the induction of colitis. Curcumin treatment was associated with amelioration of macroscopic and microscopic colitis sores, decreased MPO activity, and decreased MDA levels in acetic acid-induced colitis. Furthermore, oral curcumin supplementation clearly prevented programmed cell death and restored immunreactivity of MAPKs in the colons of colitic rats. The results of this study suggest that oral curcumin treatment decreases colon injury and is associated with decreased inflammatory reactions, lipid peroxidation, apoptotic cell death, and modulating p38- and JNK-MAPK pathways.

Topics: Acetic Acid; Animals; Anti-Inflammatory Agents; Antioxidants; Apoptosis; Colitis, Ulcerative; Colon; Curcuma; Curcumin; Dietary Supplements; Disease Models, Animal; Inflammation; Intestinal Mucosa; JNK Mitogen-Activated Protein Kinases; Male; Malondialdehyde; MAP Kinase Signaling System; Mitogen-Activated Protein Kinases; Oxidative Stress; p38 Mitogen-Activated Protein Kinases; Peroxidase; Phytotherapy; Plant Extracts; Rats; Rats, Wistar; Signal Transduction

Chronic alcohol intake is known to induce the selective neuronal damage associated with increase oxidative-nitrosative stress and activation of inflammatory cascade finally resulting in cognitive deficits. In the present study, we investigated the protective effect of curcumin, a potent natural anti-oxidant and anti-inflammatory molecule against chronic alcohol-induced cognitive dysfunction and nuclear factor kappa beta (NF-κβ) mediated inflammatory signaling in the brain of rats chronically administered ethanol. Male Wistar rats were given ethanol (10 g/kg; oral gavage) for 10 weeks, and treated with curcumin (15, 30 and 60 mg/kg) for the same duration. Ethanol-exposed rats showed impaired spatial navigation in the Morris water maze test and poor retention in the elevated plus maze task which was coupled with enhanced acetylcholinesterase activity, increased oxidative-nitrosative stress, cytokines (tumor necrosis factor alpha (TNF-α) and interleukin-1 beta (IL-1β)), NF-kβ and caspase-3 levels in different brain regions (cerebral cortex and hippocampus) of ethanol-treated rats. Co-administration with curcumin significantly and dose-dependently prevented all the behavioral, biochemical and molecular alterations in rats chronically administered ethanol. Thus, findings from the current study demonstrates the possible involvement of oxidative-nitrosative stress mediated cytokine release and inflammatory signaling in chronic alcohol-induced cognitive dysfunction and also suggests the effectiveness of curcumin in preventing cognitive deficits associated with chronic alcohol consumption.

Topics: Acetylcholinesterase; Animals; Anti-Inflammatory Agents, Non-Steroidal; Behavior, Animal; Caspase 3; Cerebral Cortex; Cognition Disorders; Curcumin; Cytokines; Dose-Response Relationship, Drug; Drug Evaluation, Preclinical; Ethanol; Hippocampus; Inflammation; Male; Neuroprotective Agents; Nitrites; Oxidative Stress; Rats; Transcription Factor RelA

We previously reported the design and discovery of three series of 5-carbon linker-containing mono-carbonyl analogs of curcumin (MCACs) as excellent anti-inflammatory agents. In continuation of our ongoing research, we designed and synthesized the fourth series of MCACs, whose central linker is a piperid-4-one. Their inhibitory effects against IL-6 production were evaluated in lipopolysaccharide (LPS)-stimulated macrophages. Among them, compounds F8, F29, F33, F35, and F36 exhibited the IC50 values under 5 μM. The structure-activity relationship was discussed. Mechanistically, F35 and F36 dose-dependently prevented LPS-induced NF-κB and ERK activation. Finally, pretreatment with F35 and F36 significantly protected the C57B/L6 mice from LPS-induced septic death. Together, these data present a series of new analogs of curcumin as promising anti-inflammatory agents.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Cell Line; Curcumin; Dose-Response Relationship, Drug; Drug Discovery; Extracellular Signal-Regulated MAP Kinases; Gene Expression; Inflammation; Lipopolysaccharides; Macrophages; Male; Mice; Mice, Inbred C57BL; NF-kappa B; Piperidones; Sepsis; Signal Transduction; Structure-Activity Relationship; Survival Analysis

Bilateral destruction of the olfactory bulbs is known to cause behavioral changes analogous to symptoms of depression. Curcumin, a traditional Indian spice is currently being investigated in different psychiatric problems including depression. Dietary phytochemicals are currently used as an adjuvant therapy to accelerate their therapeutic efficacy. Therefore, the present study is an attempt to elucidate the neuroprotective mechanism of curcumin and its co-administration with piperine against olfactory bulbectomy induced depression in rats.. Rats undergone olfactory bulbs ablations were analyzed after post-surgical rehabilitation period of 2 weeks. Animals were then treated with different doses of curcumin (100, 200 and 400 mg/kg; p.o.), piperine (20 mg/kg; p.o.) and their combination daily for another 2 weeks. Imipramine (10 mg/kg; i.p.) served as a standard control. Various behavioral tests like forced swim test (FST), open field behaviour and sucrose preference test (SPT) were performed, followed by estimation of biochemical, mitochondrial, molecular and histopathological parameters in rat brain.. Ablation of olfactory bulbs caused depression-like symptoms as evidenced by increased immobility time in FST, hyperactivity in open field arena, and anhedonic like response in SPT along with alterations in mitochondrial enzyme complexes, increased serum corticosterone levels and oxidative damage. These deficits were integrated with increased inflammatory cytokines (TNF-α) and apoptotic factor (caspase-3) levels along with a marked reduction in neurogenesis factor (BDNF) in the brain of olfactory bulbectomized (OBX) rats. Curcumin treatment significantly and dose-dependently restored all these behavioral, biochemical, mitochondrial, molecular and histopathological alterations associated with OBX induced depression. Further, co-administration of piperine with curcumin significantly potentiated their neuroprotective effects as compared to their effects alone.. The present study highlights that curcumin along with piperine exhibits neuroprotection against olfactory bulbectomy induced depression possibly by modulating oxidative-nitrosative stress induced neuroinflammation and apoptosis.

Topics: Alkaloids; Animals; Apoptosis; Benzodioxoles; Brain; Brain-Derived Neurotrophic Factor; Caspase 3; Corticosterone; Curcumin; Depression; Disease Models, Animal; Drug Therapy, Combination; Electron Transport Chain Complex Proteins; Food Preferences; Immobilization; Inflammation; Lipid Peroxidation; Male; Mitochondria; Olfactory Bulb; Piperidines; Polyunsaturated Alkamides; Rats; Rats, Wistar; Signal Transduction; Sucrose; Tumor Necrosis Factor-alpha

To investigate whether curcumin (Cur) suppressed lipopolysaccharide (LPS)-induced inflammation in vascular smooth muscle cells (VSMCs) of rats, and to determine its molecular mechanisms.. Primary rat VSMCs were treated with LPS (1 μg/L) and Cur (5, 10, or 30 μmol/L) for 24 h. The levels of MCP-1, TNF-α, and iNOS were measured using ELISA and real-time RT-PCR. NO level was analyzed with the Griess reaction. Western-blotting was used to detect the activation of TLR4, MAPKs, IκBα, NF-κB p65, and the p47(phox) subunit of NADPH oxidase in the cells.. Treatment of VSMCs with LPS dramatically increased expression of inflammatory cytokines MCP-1 and TNF-α, expression of TLR4 and iNOS, and NO production. LPS also significantly increased phosphorylation of IκBα, nuclear translocation of NF-κB (p65) and phosphorylation of MAPKs in VSMCs. Furthermore, LPS significantly increased production of intracellular ROS, and decreased expression of p47(phox) subunit of NADPH oxidase. Pretreatment with Cur concentration-dependently attenuated all the aberrant changes in LPS-treated VSMCs. The LPS-induced overexpression of MCP-1 and TNF-α, and NO production were attenuated by pretreatment with the ERK inhibitor PD98059, the p38 MAPK inhibitor SB203580, the NF-κB inhibitor PDTC or anti-TLR4 antibody, but not with the JNK inhibitor SP600125.. Cur suppresses LPS-induced overexpression of inflammatory mediators in VSMCs in vitro via inhibiting the TLR4-MAPK/NF-κB pathways, partly due to block of NADPH-mediated intracellular ROS production.

Topics: Animals; Cells, Cultured; Curcumin; Inflammation; Lipopolysaccharides; Male; MAP Kinase Signaling System; Muscle, Smooth, Vascular; NF-kappa B; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species; Toll-Like Receptor 4

The reprogramming of cellular metabolism in cancer cells is a well-documented effect. It has previously been shown that common oncogene expression can induce aerobic glycolysis in cancer cells. However, the direct effect of an inflammatory microenvironment on cancer cell metabolism is not known. Here, we illustrate that treatment of nonmalignant (MCF-10a) and malignant (MCF-7) breast epithelial cells with low-level (10 ng/ml) tumor necrosis factor alpha (TNF-α) significantly increased glycolytic reliance, lactate export and expression of the glucose transporter 1 (GLUT1). TNF-α decreased total mitochondrial content; however, oxygen consumption rate was not significantly altered, suggesting that overall mitochondrial function was increased. Upon glucose starvation, MCF7 cells treated with TNF-α demonstrated significantly lower viability than nontreated cells. Interestingly, these properties can be partially reversed by coincubation with the anti-inflammatory agent curcumin in a dose-dependent manner. This work demonstrates that aerobic glycolysis can be directly induced by an inflammatory microenvironment independent of additional genetic mutations and signals from adjacent cells. Furthermore, we have identified that a natural dietary compound can reverse this effect.

Topics: Anti-Inflammatory Agents; Breast; Cell Line, Tumor; Curcumin; Epithelial Cells; Glucose; Glucose Transporter Type 1; Glycolysis; Humans; Inflammation; Lactic Acid; MCF-7 Cells; Mitochondria; NF-kappa B; Oxygen Consumption; Tumor Microenvironment; Tumor Necrosis Factor-alpha; Walker-Warburg Syndrome

Curcumin, the active ingredient of turmeric (Curcuma longa), has a wide range of beneficial effects including anti-inflammation and analgesia. However, poor bioavailability of curcumin hinders its clinical application. To overcome this limitation, we modified the structure of curcumin and synthesized new derivatives with favourable pharmacokinetic profiles. Recently, curcumin has been shown to have an antagonizing effect on transient receptor potential vanilloid type 1 (TRPV1) ion channels. We investigated the antinociceptive activity of KMS4034 which had the most favourable pharmacokinetics among the tested curcumin derivatives.. To evaluate the mechanism of the antinociceptive effects of KMS4034, capsaicin (I(CAP))- and heat (I(heat))-induced currents in TRPV1 expressing HEK293 cells were observed after the application of KMS4034. Nociceptive behavioural measurement using the hot-plate test, formalin test, and chronic constriction injury (CCI) model were evaluated in mice. Also, calcitonin gene-related peptide (CGRP) was stained immunohistochemically in the L4/5 dorsal horns in mice with neuropathic pain.. I(CAP) (P<0.01) and I(heat) (P<0.05) of TRPV1 were significantly blocked by 10 μM KMS4034. Behaviourally, noticeable antinociceptive effects after 10 mg kg(-1) of KMS4034 treatment were observed in the first (P<0.05) and second phases (P<0.05) of the formalin and hot-plate tests. The mechanical threshold of CCI mice treated with 10 mg kg(-1) KMS4034 was significantly increased compared with control. Immunohistochemical CGRP expression was decreased in the lamina I-II of the lumbar dorsal horns in KMS4034-treated CCI mice compared with the control (P<0.05).. KMS4034 may be an effective analgesic for various pain conditions.

Topics: Analgesics, Non-Narcotic; Animals; Calcitonin Gene-Related Peptide; Cells, Cultured; Curcumin; Drug Evaluation, Preclinical; Formaldehyde; Hot Temperature; Inflammation; Male; Mice; Mice, Inbred ICR; Neuralgia; Patch-Clamp Techniques; Physical Stimulation; Posterior Horn Cells; Reaction Time; TRPV Cation Channels

Aging is associated with chronic inflammation and oxidative stress, which both may promote age-associated disorders including cardiovascular diseases. The cardiovascular system suffers from the life-long impact of stressors, such as reactive oxygen and nitrogen species. A diet rich in vegetables and fruits, and thus phytochemicals, may extend healthy lifespan in humans, in part by improving heart health by lowering of oxidative stress and modulating signal transduction pathways. To investigate the potential impact of dietary anthocyanin-rich bilberry extract and curcumin on oxidative stress and inflammatory markers in the heart, two groups of senescence-accelerated mouse-resistant 1 (SAMR1) and senescence-accelerated mouse-prone 8 (SAMP8) mice, respectively, were fed a Western-type diet (normal control and aged control, respectively) and two groups of SAMP8 mice were fed either bilberry extract (20g/kg diet) or curcumin (500mg/kg diet) over a period of 5 months. An activation of the transcription factor nuclear factor κ B (NFκB), but no differences in the gene and protein expression of NFκB-regulated pro-inflammatory mediators, was observed in the hearts of SAMP8 compared to SAMR1 control mice. Cardiac concentrations of protein and lipid oxidation parameters were similar in SAMR1 and SAMP8 control mice and the phytochemical-fed SAMP8 mice. Our data question the suitability of the SAMP8 and SAMR1 strains as a model for age-dependent changes of pro-inflammatory cytokines and oxidative stress in the heart.

Topics: Animals; Antioxidants; Curcumin; Cytokines; Glutathione Disulfide; Heme Oxygenase-1; Inflammation; Male; Membrane Proteins; Mice; Mice, Inbred Strains; Models, Animal; Myocardium; NF-E2-Related Factor 2; NF-kappa B; Oxidative Stress; Phytochemicals; Plant Extracts; RNA, Messenger; Vaccinium myrtillus

Curcumin, a selective phosphorylase kinase inhibitor, is a naturally occurring phytochemical present in turmeric. Curcumin has been confirmed to have anti-inflammatory properties in addition to the ability to decrease the expression of pro-inflammatory cytokines in keratinocytes. The interleukin-23 (IL-23)/IL-17A cytokine axis plays a critical role in the pathogenesis of psoriasis. Here, we report that topical use of a curcumin gel formulation strongly inhibited imiquimod (IMQ)-induced psoriasis-like inflammation, the development of which was based on the IL-23/IL-17A axis. IMQ-induced epidermal hyperplasia and inflammation in BALB/c mouse ear was significantly inhibited following curcumin treatment. Real-time PCR showed that mRNA levels of IL-17A, IL-17F, IL-22, IL-1β, IL-6 and TNF-α cytokines were decreased significantly by curcumin in ear skin, an effect similar to that of clobetasol. In addition, we found that curcumin may enhance the proliferation of epidermis γδ T cells but inhibit dermal γδ T cell proliferation. We inferred that curcumin was capable of impacting the IL-23/IL-17A axis by inhibiting IL-1β/IL-6 and then indirectly down-regulating IL-17A/IL-22 production. In conclusion, curcumin can relieve the IMQ-induced psoriasis-like inflammation in a mouse model, similar to the effects of clobetasol. Therefore, we have every reason to expect that curcumin will be used in the treatment of psoriasis in the future.

Topics: Aminoquinolines; Animals; Cell Proliferation; Curcumin; Ear; Gene Expression Regulation; Imiquimod; Inflammation; Interleukin-1beta; Interleukin-6; Mice; Mice, Inbred BALB C; Nuclear Receptor Subfamily 1, Group F, Member 3; Psoriasis; Receptors, Antigen, T-Cell, gamma-delta; Receptors, CCR6; RNA, Messenger; Skin

Curcumin shows effective anti-inflammatory activities but is seldom used in clinic because of its poor solubility in water and vulnerablity to sunshine ultraviolet effect. Novel lipid vesicles have been developed as carriers for skin delivery. In this paper, lipid vesicles-propylene glycol liposomes (PGL), Ethosomes and traditional liposomes, were prepared as curcumin carriers respectively. Their morphology, particle size and encapsulation efficiency and drug release behavior in vitro were evaluated. Transdermal efficiency and deposition quantity in abdominal skin were also measured with Franz diffusion device. Carrageenan-induced paw edema was established to evaluate the anti-inflammatory effect. From the result, the particle size order of lipid vesicles was: PGL (182.4 ± 89.2 nm)Ethosomes>traditional liposomes. PGL had the best encapsulation efficiency of 92.74 ± 3.44%. From anti-inflammatory experiment, PGL showed the highest and longest inhibition on the development of paw edema, followed by Ethosomes and Traditional liposomes. With the elevated entrapment efficiency, good transdermic ability and sustained-release behavior, PGL may represent an efficient transdermal lipid vesicle for skin delivery.

Topics: Administration, Cutaneous; Animals; Anti-Inflammatory Agents; Carrageenan; Chemistry, Pharmaceutical; Curcumin; Delayed-Action Preparations; Disease Models, Animal; Drug Stability; Edema; Female; Inflammation; Kinetics; Lipids; Liposomes; Male; Particle Size; Propylene Glycol; Rats, Sprague-Dawley; Skin; Skin Absorption; Solubility; Technology, Pharmaceutical

Radiculopathy, a painful neuroinflammation that can accompany intervertebral disc herniation, is associated with locally increased levels of the pro-inflammatory cytokine tumor necrosis factor alpha (TNFα). Systemic administration of TNF antagonists for radiculopathy in the clinic has shown mixed results, and there is growing interest in the local delivery of anti-inflammatory drugs to treat this pathology as well as similar inflammatory events of peripheral nerve injury. Curcumin, a known antagonist of TNFα in multiple cell types and tissues, was chemically modified and conjugated to a thermally responsive elastin-like polypeptide (ELP) to create an injectable depot for sustained, local delivery of curcumin to treat neuroinflammation. ELPs are biopolymers capable of thermally-triggered in situ depot formation that have been successfully employed as drug carriers and biomaterials in several applications. ELP-curcumin conjugates were shown to display high drug loading, rapidly release curcumin in vitro via degradable carbamate bonds, and retain in vitro bioactivity against TNFα-induced cytotoxicity and monocyte activation with IC50 only two-fold higher than curcumin. When injected proximal to the sciatic nerve in mice via intramuscular (i.m.) injection, ELP-curcumin conjugates underwent a thermally triggered soluble-insoluble phase transition, leading to in situ formation of a depot that released curcumin over 4days post-injection and decreased plasma AUC 7-fold.

Topics: Animals; Anti-Inflammatory Agents; Cell Line, Tumor; Curcumin; Delayed-Action Preparations; Drug Delivery Systems; Elastin; Female; Genetic Engineering; Hot Temperature; Humans; Inflammation; Intervertebral Disc Displacement; Mice; Mice, Inbred C57BL; Peptides; Sciatic Nerve; U937 Cells

Curcumin is a molecule found in turmeric root that has anti-inflammatory, antioxidant, and anti-tumor properties and has been widely used as both an herbal drug and a food additive to treat or prevent neurodegenerative diseases. To explore whether curcumin is able to ameliorate HIV-1-associated neurotoxicity, we treated a murine microglial cell line (N9) and primary rat cortical neurons with curcumin in the presence or absence of neurotoxic HIV-1 gp120 (V3 loop) protein. We found that HIV-1 gp120 profoundly induced N9 cells to produce reactive oxygen species (ROS), tumor necrosis factor-α (TNF-α) and monocyte chemoattractant protein-1 (MCP-1). HIV-1 gp120 also induced apoptosis of primary rat cortical neurons. Curcumin exerted a powerful inhibitory effect against HIV-1 gp120-induced neuronal damage, reducing the production of ROS, TNF-α and MCP-1 by N9 cells and inhibiting apoptosis of primary rat cortical neurons. Curcumin may exert its biological activities through inhibition of the delayed rectification and transient outward potassium (K(+)) current, as curcumin effectively reduced HIV-1 gp120-mediated elevation of the delayed rectification and transient outward K(+) channel current in neurons. We conclude that HIV-1 gp120 increases ROS, TNF-α and MCP-1 production in microglia, and induces cortical neuron apoptosis by affecting the delayed rectification and transient outward K(+) channel current. Curcumin reduces production of ROS and inflammatory mediators in HIV-1-gp120-stimulated microglia, and protects cortical neurons against HIV-1-mediated apoptosis, most likely through inhibition of HIV-1 gp120-induced elevation of the delayed rectification and transient outward K(+) current.

Topics: Animals; Apoptosis; Cell Line; Cell Survival; Cerebral Cortex; Curcumin; Cytoprotection; HIV Envelope Protein gp120; Inflammation; Inflammation Mediators; Mice; Microglia; Neurons; Potassium; Potassium Channels, Voltage-Gated; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species

Viral myocarditis is an inflammation of the myocardium, and coxsackievirus B3 (CVB3) is one of the most important etiologic agents. Curcumin is an active ingredient of Curcumin longa, which has been used as a traditional Chinese herb for the treatment of various inflammatory diseases. The aim of this study was to explore the therapeutic effect of curcumin on CVB3-induced myocarditis and the underlying mechanism. Our results showed that treatment with curcumin could significantly attenuate CVB3-induced myocarditis, as demonstrated by improved weight loss, increased survival rate, reduced serological level cardiac enzymes, and improved heart histopathology. Of importance, curcumin administration was revealed to significantly reduce the systemic and local myocardial expression of proinflammatory cytokines, such as tumor necrosis factor-α, interleukin (IL) 6, and IL-1β, in the CVB3-infected mice. Further study showed that curcumin treatment significantly inhibited the CVB3-induced activation of nuclear factor-κB (NF-κB), a key transcription factor in the pathogenesis of inflammation, in a phosphatidylinositol 3 kinase (PI3K)/Akt pathway-dependent manner. These data indicate that curcumin has protective effect against CVB3-induced myocarditis by inhibiting PI3K/Akt/NF-κB signaling pathway and thus reducing the inflammatory response.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Coxsackievirus Infections; Curcumin; Cytokines; Inflammation; Male; Mice; Mice, Inbred BALB C; Myocarditis; NF-kappa B; Phosphatidylinositol 3-Kinase; Proto-Oncogene Proteins c-akt; Signal Transduction; Tumor Necrosis Factor-alpha

Puerarin (PU) and curcumin (CU), used commonly in traditional Chinese medicine and Ayurveda, have been shown to possess potent anti-inflammatory, anti-oxidation, and neuro-protective properties. Despite the experimental success of CU and PU in in vitro and animal models, their effectiveness has not yet been demonstrated in clinical trials, possibly because of their poor bioavailability. We hypothesized that gold nanoparticle (AuNP)-formulated PU (PU-AuNP), CU (CU-AuNP), or a combination of PU and CU (PU-CU-AuNP) were a more effective and nontoxic alternative to their bulk (nonformulated) counterparts. To test the hypothesis, bioavailability, therapeutic potency, and toxicity of bulk CU and/or PU were compared with those of their nanotized counterparts in rats subjected to the lipopolysaccharide (LPS)-induced inflammation. This study showed that a 20-mg/kg dose of bulk PU or a mixture of PU and CU did not, while their nanotized counterparts, PU-AuNP, CU-AuNP, or PU-CU-AuNP, effectively suppressed the LPS-induced inflammation and cytotoxicity in rats. In addition, PU-CU-AuNP was more potent than PU-AuNP or CU-AuNP alone. The blank AuNP (bAuNP) at ≤40 mg/kg dose did not cause any adverse effects (blood and brain lactic acid concentrations, kidney function, and neuronal apoptosis were measured) in animals. Therefore, the present observations suggest that a bi-functional AuNP loaded with CU and PU may effectively suppress the LPS-induced inflammation and cytotoxicity provided the following conditions are met: (1) The AuNP dose is at or below the no-effect dose; (2) the nanoparticles release a therapeutic dose of CU and PU in vivo; and (3) the active ingredients are released into the intracellular component of the brain.

Topics: Animals; Anti-Inflammatory Agents; Apoptosis; Curcumin; Humans; Inflammation; Isoflavones; Lipopolysaccharides; Male; Nanoparticles; Neurons; Plant Extracts; Pueraria; Rats; Rats, Sprague-Dawley

Curcumin, extracted from the rhizome of Curcuma longa, is known to possess anti-inflammatory activities. Despite the fact that neutrophils are key player cells in inflammation, the role of curcumin on neutrophil cell biology is not well documented and, in particular, how curcumin can alter primed neutrophils is unknown. In addition, the effect of curcumin on agent-induced neutrophilic inflammation is not well documented. Here, we demonstrated that curcumin inhibited formyl-methionyl-leucyl-phenylalanine (fMLP)- or lipopolysaccharide (LPS)-induced suppression of human neutrophil apoptosis. In addition, we found that curcumin reversed the ability of phorbol myristate acetate (PMA) to induce reactive oxygen species as assessed by flow cytometry using the CM-H2DCF-DA probe. Using an antibody array approach, curcumin was found to inhibit LPS-induced cytokine production, including MIP-1α, MIP-1β, IL-6, IL-8 (CXCL-8) and GRO-α. The inhibitory effect of curcumin on IL-8 production was confirmed by ELISA. Using both an electrophoretic mobility shift assay and a TransFactor p50 NF-κB ELISA, we demonstrated that curcumin inhibited LPS-induced NF-κB activation. In vivo, using the murine air pouch model of acute inflammation, we demonstrated that intraperitoneal administration of curcumin inhibited LPS-induced neutrophilic infiltration in vivo. As assessed by a murine antibody array approach, curcumin was found to decrease the local production of several cytokines/chemokines induced by LPS, including, but not limit to, MIP-1α and MIP-1β. We conclude that curcumin possesses potent modulatory activities on primed or agent-induced human neutrophils in vitro and that it possesses important anti-inflammatory activities in vivo by inhibiting LPS-induced neutrophilic inflammation.

Topics: Animals; Anti-Inflammatory Agents; Apoptosis; Cells, Cultured; Curcumin; Cytokines; Female; Humans; Inflammation; Interleukin-8; Lipopolysaccharides; Mice; Neutrophils; NF-kappa B; Reactive Oxygen Species

Supra-nutritional doses of curcumin, derived from the spice Curcuma longa, have been proposed as a potential treatment of inflammation and metabolic disorders related to obesity. The aim of the present study was to test whether Curcuma longa extract rich in curcumin and associated with white pepper (Curcuma-P®), at doses compatible with human use, could modulate systemic inflammation in diet-induced obese mice. We questioned the potential relevance of changes in adiposity and gut microbiota in the effect of Curcuma-P® in obesity.. Mice were fed either a control diet (CT), a high fat (HF) diet or a HF diet containing Curcuma longa extract (0.1 % of curcumin in the HF diet) associated with white pepper (0.01 %) for four weeks. Curcumin has been usually combined with white pepper, which contain piperine, in order to improve its bioavailability. This combination did not significantly modify body weight gain, glycemia, insulinemia, serum lipids and intestinal inflammatory markers. Tetrahydrocurcumin, but not curcumin accumulated in the subcutaneous adipose tissue. Importantly, the co-supplementation in curcuma extract and white pepper decreased HF-induced pro-inflammatory cytokines expression in the subcutaneous adipose tissue, an effect independent of adiposity, immune cells recruitment, angiogenesis, or modulation of gut bacteria controlling inflammation.. These findings support that nutritional doses of Curcuma longa, associated with white pepper, is able to decrease inflammatory cytokines expression in the adipose tissue and this effect could be rather linked to a direct effect of bioactive metabolites reaching the adipose tissue, than from changes in the gut microbiota composition.

Topics: Animals; Blood Glucose; Cell Movement; Curcuma; Curcumin; Cytokines; Diet, High-Fat; Dietary Fats; Dietary Supplements; Inflammation; Insulin; Leukocytes; Male; Mice; Mice, Inbred C57BL; Microbiota; Obesity; Piper nigrum; Plant Extracts; Subcutaneous Fat; Weight Gain

Hepatic ischemia-reperfusion (IR) injury is a clinical problem that leads to cellular damage and organ dysfunction mediated mainly via production of reactive oxygen species and inflammatory cytokines. Vinpocetine has long been used in cerebrovascular disorders. This study aimed to explore the protective effect of vinpocetine in IR injury to the liver. Ischemia was induced in rats by clamping the common hepatic artery and portal vein for 30 min followed by 30 min of reperfusion. Serum transaminases and liver lactate dehydrogenase (LDH) activities, liver inflammatory cytokines, oxidative stress biomarkers, and liver histopathology were assessed. IR resulted in marked histopathology changes in liver tissues coupled with elevations in serum transaminases and liver LDH activities. IR also increased the production of liver lipid peroxides, nitric oxide, and inflammatory cytokines interleukin-1β and interleukin-6, in parallel with a reduction in reduced glutathione and interleukin-10 in the liver. Pretreatment with vinpocetine protected against liver IR-induced injury, in a dose-dependent manner, as evidenced by the attenuation of oxidative stress as well as inflammatory and liver injury biomarkers. The effects of vinpocetine were comparable with that of curcumin, a natural antioxidant, and could be attributed to its antioxidant and anti-inflammatory properties.

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Biomarkers, Pharmacological; Curcumin; Cytokines; Glutathione; Inflammation; Interleukin-10; Interleukin-1beta; Interleukin-6; L-Lactate Dehydrogenase; Liver; Male; Oxidative Stress; Rats; Rats, Wistar; Reperfusion Injury; Transaminases; Vinca Alkaloids

Curcumin, an active ingredient of turmeric, is proved to be a potential candidate of controlling inflammation and bone resorption, but few reports are on the periodontitis. The purpose of this study was to evaluate whether the intra-gastric administration of curcumin could inhibit the inflammation and alveolar bone resorption in rats following ligature-induced experimental periodontitis.. Male Wistar rats were randomly divided into three groups: no ligature placement and administration of vehicle, ligature placement and administration of vehicle, ligature placement and administration of curcumin. After the animals were sacrificed, their mandibles were collected for morphological, histological and immunohistochemical analysis; their gingival tissues were collected for cytokine measurements.. Bone resorption was significantly higher in the experimental periodontitis animals treated with vehicle compared with the curcumin-treated group or the control group. Furthermore, receptor activator of nuclear factor-κB ligand (RANKL), receptor activator of nuclear factor-κB (RANK), osteoprotegerin (OPG), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) expression levels were higher in the experimental periodontitis animals treated with vehicle compared with the curcumin treated group or the control group. CONCLUSIONS. Curcumin may decrease alveolar bone loss in the experimental periodontitis rats via suppressing the expression of RANKL/RANK/OPG and its anti-inflammatory properties.

Topics: Animals; Curcumin; Immunohistochemistry; Inflammation; Inflammation Mediators; Male; Osteoporosis; Periodontitis; Rats; Rats, Wistar

There is increasing evidence indicating that inflammatory processes are involved in the development and progression of diabetic complications. However, effective anti-inflammatory treatments for patients who have diabetic complications have yet been practically identified. Curcumin is a main component of Curcuma longa with numerous pharmacological activities. Previously, we synthesized a novel curcumin analogue (B06) that exhibited an improved pharmacokinetic and enhanced anti-inflammatory activity compared to curcumin. The present study aimed to test the hypothesis that B06 may reduce high-glucose-induced inflammation and inflammation-mediated diabetic complications. In vitro, pretreatment with B06 at a concentration of 5 μM significantly reduced the high-glucose-induced overexpression of inflammatory cytokines in macrophages. This anti-inflammatory activity of B06 is associated with its inhibition of c-Jun N-terminal kinase/nuclear factor κB activation. In vivo, despite that B06 administration at 0.2 mg · kg(-1) · d(-1) for 6 weeks did not affect the blood glucose profile of diabetic rats, the B06-treated animals displayed significant decreases in inflammatory mediators in the serum, kidney, and heart and renal macrophage infiltration. This was accompanied with an attenuation of diabetes-induced structural and functional abnormalities in the kidney and heart. Taken together, these data suggest that the novel derivative B06 might be a potential therapeutic agent for diabetic complications via an anti-inflammatory mechanism and support the potential application in diabetic complication therapy via anti-inflammatory strategy.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Bromobenzenes; Curcumin; Diabetes Mellitus, Experimental; Diabetic Nephropathies; Dose-Response Relationship, Drug; Glucose; Heart; Inflammation; Inflammation Mediators; Interleukin-6; JNK Mitogen-Activated Protein Kinases; Kidney; Macrophages, Peritoneal; Male; Mice; Mice, Inbred ICR; Myocardium; NF-kappa B; Pentanones; Protective Agents; Rats; Rats, Sprague-Dawley; Tumor Necrosis Factor-alpha

We hypothesized that curcumin, by increasing the expression of nuclear factor-erythroid-2-related factor 2 (Nrf2), could reduce oxidative stress, inflammation, and renal fibrosis in remnant kidney.. Sprague-Dawley rats were subjected to 5/6 nephrectomy and randomly assigned to untreated (Nx), curcumin-treated (75 mg/kg/day, orally), and telmisartan-treated groups (10 mg/kg/day, orally; as positive control). Sham-operated rats also served as controls. Five/sixth nephrectomy caused renal dysfunction, as evidenced by elevated proteinuria, blood urea nitrogen, and plasma creatinine, and decreased creatinine clearance that were ameliorated by curcumin or telmisartan treatment. The Nx rats demonstrated reduced Nrf2 protein expression, whereas the Kelch-like ECH-associated protein 1 was upregulated and heme oxygenase-1 level was significantly diminished. Consequently, Nx animals had significantly higher kidney malondialdehyde concentration and lower glutathione peroxidase activity, which was associated with the upregulation of nicotinamide adenine dinucleotide phosphatase oxidase subunit (p67(phox) and p22(phox) ), NF-kappaB p65, TNF-α, TGF-β1, cyclooxygenase-2, and fibronectin accumulation in remnant kidney. Interestingly, all of these changes were ameliorated by curcumin or telmisartan.. These findings demonstrate that, by modulating Nrf2-Keap1 pathway, the curcumin effectively attenuates oxidative stress, inflammation, and renal fibrosis, which suggest that curcumin hold promising potential for safe treatment of chronic kidney disease.

Topics: Animals; Benzimidazoles; Benzoates; Blood Pressure; Blood Urea Nitrogen; Creatinine; Curcumin; Cyclooxygenase 2; Fibronectins; Fibrosis; Heme Oxygenase (Decyclizing); Inflammation; Intracellular Signaling Peptides and Proteins; Kelch-Like ECH-Associated Protein 1; Kidney; Kidney Diseases; Male; Nephrectomy; NF-E2-Related Factor 2; NF-kappa B; Oxidative Stress; Proteinuria; Rats; Rats, Sprague-Dawley; Signal Transduction; Telmisartan; Transforming Growth Factor beta1; Tumor Necrosis Factor-alpha

Inflammatory mechanisms may play an important role in the pathogenesis of cisplatin-induced nephrotoxicity. Curcumin is an orange-yellow polyphenol present in curry spice and has anti-inflammatory and antioxidant effects. The purpose of this study was to determine the protective effects of curcumin on cisplatin-induced nephrotoxicity. Mice were randomly divided into four groups: control, cisplatin, cisplatin + curcumin and curcumin. Mice were given cisplatin (20 mg/kg body weight, intraperitoneally) with or without curcumin treatment (100 mg/kg body weight, intraperitoneally, immediately after cisplatin injection). Serum and renal tumor necrosis factor (TNF)-alpha and renal monocyte chemoattractant protein (MCP)-1 concentrations, intercellular adhesion molecule-1 (ICAM-1) mRNA expression in kidney, renal function and histological changes were determined 72 h after cisplatin injection. Serum TNF-alpha concentration in the cisplatin + curcumin group significantly decreased compared with that in the cisplatin group. Renal TNF-alpha and MCP-1 concentrations and ICAM-1 mRNA expression in kidney in the cisplatin + curcumin group also significantly decreased compared with those in the cisplatin group. Consequently, cisplatin-induced renal dysfunction and renal tubular necrosis scores were attenuated by curcumin treatment. These results indicate that curcumin acts to reduce cisplatin-induced nephrotoxicity through its anti-inflammatory effects. Thus, curcumin may become a new therapeutic candidate for the treatment of cisplatin-induced nephrotoxicity.

Topics: Acute Kidney Injury; Animals; Anti-Inflammatory Agents; Antineoplastic Agents; Antioxidants; Chemokine CCL2; Cisplatin; Curcumin; Inflammation; Intercellular Adhesion Molecule-1; Kidney; Male; Mice; Mice, Inbred C57BL; Tumor Necrosis Factor-alpha

Curcumin is a widely used spice with anti-inflammatory and anticancer properties. It has been reported to have beneficial effects in experimental colitis. This study explored whether curcumin improves colonic inflammation in a rat colitis model through inhibition of the TLR4/NF-κB signaling pathway and IL-27 expression. After induction of colitis with 2,4,6-trinitrobenzene sulfonic acid, rats were intragastrically administered with curcumin or sulfasalazine daily for one week. Rat intestinal mucosa was collected for evaluation of the disease activity index, colonic mucosa damage index, and histological score. Myeloperoxidase activity was detected by immunohistochemistry, and mRNA and protein expression levels of TLR4, NF-κB, and IL-27 in colonic mucosa were detected by RT-PCR and Western blot. Compared with the untreated colitis group, the curcumin-treated group showed significant decreases in the disease activity index, colonic mucosa damage index, histological score, myeloperoxidase activity, and expressions of NF-κB mRNA, IL-27 mRNA, TLR4 protein, NF-κB p65 protein, and IL-27 p28 protein (p < 0.05). TLR4 mRNA expression did not differ between groups. Disease activity index decreased more rapidly in the curcumin-treated group than in the sulfasalazine-treated group (p < 0.05). There was no significant difference in TLR4, NF-κB, and IL-27 mRNA and proteins between curcumin-treated and sulfasalazine-treated groups. Curcumin shows significant therapeutic effects on 2,4,6-trinitrobenzene sulfonic acid-induced colitis that are comparable to sulfasalazine. The anti-inflammatory actions of curcumin on colitis may involve inhibition of the TLR4/NF-κB signaling pathway and of IL-27 expression.

Topics: Animals; Anti-Inflammatory Agents; Colitis; Colon; Curcumin; Disease Models, Animal; Gastrointestinal Agents; Inflammation; Interleukins; Intestinal Mucosa; Male; NF-kappa B; Peroxidase; Random Allocation; Rats; Signal Transduction; Sulfasalazine; Toll-Like Receptor 4; Transcription Factor RelA; Trinitrobenzenesulfonic Acid

To examine the effect of the zedoary essential component-eluting stent (ZES) on a porcine coronary neointimal formation.. ZES, sirolimus-eluting stents (SES), and bare metal stents (BMS) were randomly implanted in three different major epicardial vessels in 36 balloon-injured pigs. Coronary angiography, optical coherence tomography, and histomorphological analysis were used to determine antihyperplasia effects.. ZES and SES had a significantly larger lumen diameter and area, and reduced diameter and area of stenosis in arteries at 30 and 90 days compared with arteries implanted with BMS (P<0.01). Histomorphometric analysis showed moderate inflammatory responses, such as infiltration of mononuclear cells, lymphocytes, and multinucleated giant cells in some arteries with SES compared with ZES (P<0.05). Injury scores were not different among the three groups at 30 and 90 days. The endothelialization score in the SES group was 2.69 ± 0.42 at 30 days and 2.83 ± 0.39 at 90 days compared with the ZES and BMS groups (both were 3.00 ± 0.00 at either 30 or 90 days, P<0.05). Well developed endothelium was observed in the ZES group, while incomplete endothelium and inflammatory cells were observed with stent struts partly naked at the vessel lumen in the SES group.. The ZES inhibits neointimal hyperplasia with good endothelia coverage in the porcine balloon injury coronary model.

Topics: Animals; Coated Materials, Biocompatible; Coronary Stenosis; Coronary Vessels; Curcuma; Endothelium, Vascular; Inflammation; Microscopy, Electron, Scanning; Neointima; Prosthesis Implantation; Stents; Sus scrofa; Time Factors

Curcumin is a pleiotropic molecule against inflammatory related diseases. However, poor bioavailability greatly limits its application in clinic. Our previous study synthesized and evaluated a hydrosoluble mono-carbonyl analogue of curcumin, (2E,5E)-2,5-bis(4-(3-(dimethylamino)-propoxy)benzylidene)cyclopentanone (A13). In the present study, we further evaluated the anti-inflammatory effect of A13 in vivo. In lipopolysaccharide-challenged mice, pretreatment of A13 (15 mg/kg, i.v.) attenuated the increase of plasma level of NO, TNF-α, and IL-6, significantly inhibited the increase of hepatic inflammatory gene transcription, and improved pulmonary damages. In addition, A13 (10 or 30 mg/kg, i.p.) reduced vascular permeability in Institute of Cancer Research mice and inhibited pain reaction in chemically induced inflammatory models. Together, A13 exhibits anti-inflammatory activities both in vitro and in vivo by the inhibition of various inflammatory mediators.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Capillary Permeability; Cells, Cultured; Curcumin; Cyclopentanes; Inflammation; Inflammation Mediators; Interleukin-6; Lipopolysaccharides; Liver; Lung; Macrophage Activation; Macrophages; Macrophages, Peritoneal; Male; Mice; Mice, Inbred C57BL; Mice, Inbred ICR; Nitric Oxide; Pneumonia; Transcription, Genetic; Tumor Necrosis Factor-alpha

The present study aimed to determine whether curcumin isolated from the rhizome of Curcuma longa Linn could inhibit di-(2-ethylhexyl) phthalate (DEHP)-induced allergic inflammatory responses in human umbilical vein endothelial cells (HUVECs). We found that DEHP dose-dependently elevated adhesion molecule-1 (ICAM-1) protein level within 15-30 min, which was independent of de novo protein synthesis. And a late-phase induction of ICAM-1 was observed within 8 h treatment of DEHP via de novo protein synthesis through transcription and translation. DEHP also increased the expression of interleukin (IL)-8 in a time- and dose-dependent manner. Pretreatment with curcumin dose-dependently decreased DEHP-induced expression of ICAM-1 and IL-8 as well as phosphorylation of ERK1/2 and p38. Preincubation with ERK1/2 inhibitor (PD98059) or p38 inhibitor (SB203580) markedly blocked DEHP-stimulated activation of ICAM-1 and IL-8. We suggest that curcumin inhibits DEHP-induced expression of ICAM-1 and IL-8 through ERK and p38 MAPK signaling pathways in HUVECs and may contribute to ameliorate pathologies of DEHP-related allergic disorders.

Topics: Cell Line; Cell Survival; Curcumin; Diethylhexyl Phthalate; Endothelium, Vascular; Extracellular Signal-Regulated MAP Kinases; Flavonoids; Human Umbilical Vein Endothelial Cells; Humans; Imidazoles; Inflammation; Intercellular Adhesion Molecule-1; Interleukin-8; MAP Kinase Signaling System; Medicine, Chinese Traditional; p38 Mitogen-Activated Protein Kinases; Phosphorylation; Pyridines; RNA, Messenger

This study investigated the potential antinociceptive efficacy of a novel synthetic curcuminoid analogue, 2,6-bis-(4-hydroxy-3-methoxybenzylidene)cyclohexanone (BHMC), using chemical- and thermal-induced nociception test models in mice. BHMC (0.03, 0.1, 0.3 and 1.0 mg/kg) administered via intraperitoneal route (i.p.) produced significant dose-related inhibition in the acetic acid-induced abdominal constriction test in mice with an ID(50) of 0.15 (0.13-0.18) mg/kg. It was also demonstrated that BHMC produced significant inhibition in both neurogenic (first phase) and inflammatory phases (second phase) of the formalin-induced paw licking test with an ID(50) of 0.35 (0.27-0.46) mg/kg and 0.07 (0.06-0.08) mg/kg, respectively. Similarly, BHMC also exerted significant increase in the response latency period in the hot-plate test. Moreover, the antinociceptive effect of the BHMC in the formalin-induced paw licking test and the hot-plate test was antagonized by pre-treatment with the non-selective opioid receptor antagonist, naloxone. Together, these results indicate that the compound acts both centrally and peripherally. In addition, administration of BHMC exhibited significant inhibition of the neurogenic nociception induced by intraplantar injections of glutamate and capsaicin with ID(50) of 0.66 (0.41-1.07) mg/kg and 0.42 (0.38-0.51) mg/kg, respectively. Finally, it was also shown that BHMC-induced antinociception was devoid of toxic effects and its antinociceptive effect was associated with neither muscle relaxant nor sedative action. In conclusion, BHMC at all doses investigated did not cause any toxic and sedative effects and produced pronounced central and peripheral antinociceptive activities. The central antinociceptive activity of BHMC was possibly mediated through activation of the opioid system as well as inhibition of the glutamatergic system and TRPV1 receptors, while the peripheral antinociceptive activity was perhaps mediated through inhibition of various inflammatory mediators.

Topics: Analgesics; Animals; Curcumin; Cyclohexanones; Disease Models, Animal; Dose-Response Relationship, Drug; Inflammation; Inflammation Mediators; Inhibitory Concentration 50; Injections, Intraperitoneal; Male; Mice; Mice, Inbred BALB C; Naloxone; Narcotic Antagonists; Pain; Toxicity Tests, Acute

This study was designed to identify the inhibitory effect of curcumin on ox-LDL-induced monocyte chemoattractant protein-1 (MCP-1) production and investigated whether the effects are mediated by mitogen-activated protein kinase (MAPK) and NF-κB pathways in rat vascular smooth muscle cells (VSMCs).. The VSMCs cells were pretreated with curcumin, before stimulation with ox-LDL. The ox-LDL-induced MCP-1 expression was determined by enzyme-linked immunosorbent assay (ELISA) and reverse transcription-polymerase chain reaction (RT-PCR). Intracellular signaling was investigated by Western blot.. The concentrations of MCP-1 in cell supernatant and were upregulated by ox-LDL in a dose- and time-dependent manner. Additionally, curcumin decreased the expression of MCP-1 in a dose-dependent manner under treatment with ox-LDL (100 μg/ml). Signal transduction studies indicated that the ox-LDL-induced MCP-1 expression in VSMCs could be partly reversed by the inhibitor of p38 MAPK (SB203580) and NF-κB (BAY11-7082), whereas the ERK inhibitor (PD98059) and the JNK inhibitor (SP600125) had no effect. Western blot revealed that curcumin reduced ox-LDL- induced p38 MAPK phosphorylation and nuclear NF-κB p65 protein at the indicated concentration.. Curcumin suppresses ox-LDL-induced MCP-1 expression in VSMCs via the p38 MAPK and NF-κB pathways, which suggests that the anti-inflammatory effect of curcumin is related to the down-regulation of MCP-1 expression and offers a new theoretical basis in the anti-inflammatory effects of curcumin.

Topics: Animals; Aorta; Cell Nucleus; Cell Survival; Chemokine CCL2; Curcumin; Dose-Response Relationship, Drug; Enzyme Inhibitors; Gene Expression Regulation; Inflammation; Lipoproteins, LDL; Male; Muscle, Smooth, Vascular; NF-kappa B; p38 Mitogen-Activated Protein Kinases; Rats; Rats, Sprague-Dawley; Time Factors

Previously, we showed that curcumin prevents chronic kidney disease (CKD) development in ⅚ nephrectomized (Nx) rats when given within 1 wk after Nx (Ghosh SS, Massey HD, Krieg R, Fazelbhoy ZA, Ghosh S, Sica DA, Fakhry I, Gehr TW. Am J Physiol Renal Physiol 296: F1146-F1157, 2009). To better mimic the scenario for renal disease in humans, we began curcumin and enalapril therapy when proteinuria was already established. We hypothesized that curcumin, by blocking the inflammatory mediators TNF-α and IL-1β, could also reduce cyclooxygenase (COX) and phospholipase expression in the kidney. Nx animals were divided into untreated Nx, curcumin-treated, and enalapril-treated groups. Curcumin (75 mg/kg) and enalapril (10 mg/kg) were administered for 10 wk. Renal dysfunction in the Nx group, as evidenced by elevated blood urea nitrogen, plasma creatinine, proteinuria, segmental sclerosis, and tubular dilatation, was comparably reduced by curcumin and enalapril, with only enalapril significantly lowering blood pressure. Compared with controls, Nx animals had higher plasma/kidney TNF-α and IL-1β, which were reduced by curcumin and enalapril treatment. Nx animals had significantly elevated kidney levels of cytosolic PLA(2), calcium-independent intracellular PLA(2), COX 1, and COX 2, which were comparably reduced by curcumin and enalapril. Studies in mesangial cells and macrophages were carried out to establish that the in vivo increase in PLA(2) and COX were mediated by TNF-α and IL-1β and that curcumin, by antagonizing the cytokines, could significantly reduce both PLA(2) and COX. We conclude that curcumin ameliorates CKD by blocking inflammatory signals even if it is given at a later stage of the disease.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Antihypertensive Agents; Curcumin; Enalapril; Inflammation; Inflammation Mediators; Interleukin-1beta; Kidney; Nephrectomy; Phospholipases; Prostaglandin-Endoperoxide Synthases; Rats; Renal Insufficiency; Tumor Necrosis Factor-alpha

Curcuma longa is a perennial member of the Zingiberaceae family, and cultivated mainly in India, and Southeast Asia. The hypothesis for this study is that turmeric will have distinctive effects from curcumin due to the presence of other bioactive compounds. Thirty Eight-week old Sprague-Dawley rats were separated into three oral feeding groups. Group 1, standard rat chow, Control diet - AIN 93M, group 2 - Curcumin - 700ppm or 0.7g/kg diet, and group 3 - Turmeric - 14,000ppm or 14g/kg diet for a total of 3weeks. One group of rats were feed all three diets only and another group underwent esophagoduodenal anastomosis to evaluate the effects of bioavailability. Curcumin diet did not increase the transcription of mRNA of TNF-alpha, IL-6, iNOS, and COX-2. The average fold change in the mRNAs level was not significant. Whereas turmeric diet increases the levels of IL-6 (1.9-fold, p=0.05), iNOS (4.39-fold, p=0.02), IL-8 (3.11-fold, p=0.04), and COX-2 (2.02-fold, p=0.05), suggesting that turmeric either was more bioavailable or had more affect on pro-inflammatory genes compare to curcumin diet. We have demonstrated the molecular effects of curcumin and turmeric in the role as an anti-inflammatory therapy. However, significant bioavailable differences do occur and must be considered in further chemopreventative investigative trials the setting of reflux esophagitis, Barrett's esophagus, and other upper gastrointestinal cancers.

Topics: Animals; Antioxidants; Biological Availability; Biomarkers; Curcuma; Curcumin; Gene Expression Regulation; Inflammation; Plant Roots; Rats; Rats, Sprague-Dawley

Inflammation and hepatic stellate cell (HSC) activation are the most crucial steps in the formation of hepatic fibrosis. Hepatocytes damaged by viral or bacterial infection, alcohol or toxic chemicals initiate an inflammatory response that activates collagen production by HSCs. Recent studies indicate curcumin has liver-protective effects due to its anti-inflammatory, antioxidant and anticancer activities; however, the mechanisms are not well understood. In this study, we show that curcumin protected against hepatic fibrosis in BALB/c mice in vivo by inhibiting HSC activation, inflammatory responses and inducing apoptosis of damaged hepatocytes. Using the thioacetamide (TAA)-induced hepatic fibrosis animal model, we found that curcumin treatment up-regulated P53 protein expression and Bax messenger RNA (mRNA) expression and down-regulated Bcl-2 mRNA expression. Together, these responses increased hepatocyte sensitivity to TAA-induced cytotoxicity and forced the damaged cells to undergo apoptosis. Enhancing the tendency of damaged hepatocytes to undergo apoptosis may be the protective mechanism whereby curcumin suppresses inflammatory responses and hepatic fibrogenesis. These results provide a novel insight into the cause of hepatic fibrosis and the cytoprotective effects curcumin has on hepatic fibrosis suppression.

Topics: Animals; Antineoplastic Agents; Antioxidants; Apoptosis; bcl-2-Associated X Protein; Cell Line; Cell Proliferation; Curcumin; DNA Damage; Gene Expression Regulation; Hepatic Stellate Cells; Hepatocytes; In Situ Nick-End Labeling; Inflammation; Liver; Liver Cirrhosis; Male; Mice; Mice, Inbred BALB C; RNA, Messenger; Thioacetamide; Tumor Suppressor Protein p53

Mechanisms underlying the attenuation of body weight gain and insulin resistance in response to high fat diet (HFD) by the curry compound curcumin need to be further explored. Although the attenuation of the inflammatory pathway is an accepted mechanism, a recent study suggested that curcumin stimulates Wnt signaling pathway and hence suppresses adipogenic differentiation. This is in contrast with the known repressive effect of curcumin on Wnt signaling in other cell lineages.. We conducted the examination on low fat diet, or HFD fed C57BL/6J mice with or without curcumin intervention for 28 weeks. Curcumin significantly attenuated the effect of HFD on glucose disposal, body weight/fat gain, as well as the development of insulin resistance. No stimulatory effect on Wnt activation was observed in the mature fat tissue. In addition, curcumin did not stimulate Wnt signaling in vitro in primary rat adipocytes. Furthermore, curcumin inhibited lipogenic gene expression in the liver and blocked the effects of HFD on macrophage infiltration and the inflammatory pathway in the adipose tissue.. We conclude that the beneficial effect of curcumin during HFD consumption is mediated by attenuating lipogenic gene expression in the liver and the inflammatory response in the adipose tissue, in the absence of stimulation of Wnt signaling in mature adipocytes.

Topics: Adipocytes; Adipose Tissue; Adiposity; Animals; Curcumin; Dietary Fats; Dietary Supplements; Gene Expression Regulation; Glucose; Hep G2 Cells; Humans; Inflammation; Insulin; Insulin Resistance; Lipogenesis; Liver; Male; Mice; Mice, Inbred C57BL; Obesity; Phosphorylation; Proto-Oncogene Proteins c-akt; Rats; Signal Transduction; Time Factors; Weight Gain

Obesity contributes to the increased risk of liver- related morbidity and mortality. The accumulation of macrophages in adipose tissue in an inflammatory state is a hallmark of obesity-induced hepatic steatosis. In this study, we reveal the role of curcumin in the molecular mechanisms underlying inflammatory events in a model consisting of obese mice with hepatic steatosis. Obese mice fed with curcumin experienced significant weight loss and significantly reduced serum triglyceride (TG) levels. The adipose tumor necrocis factor-α, interleukin-6 (IL-6) and monocyte chemotactic protein-1 levels were significantly higher in obese mice compared to mice fed with curcumin. Compared to the obese mice, curcumin decreased the number of F4/80-positive macrophages in epididymal adipose and liver tissue. The induction of signal transducer and activator of transcription 3 phosphorylation by curcumin resulted in the downregulation of the suppressor of cytokine signaling 3 in the liver of obese mice. Curcumin decreased hepatic TG in obese mice by downregulating the gene expression of sterol regulatory element-binding protein-1c in the liver. The hepatic expression of several mitochondrial biogenesis genes decreased in the obese mice, including mitochondrial DNA (mtDNA), nuclear respiratory factor 1 (NRF1) and mitochondrial transcription factor A (Tfam), which are responsible for the lower mitochondrial respiratory chain (MRC) complex I activity and adenosine triphosphate production. By contrast, obese mice treated with curcumin showed normalized mtDNA, NRF1 and Tfam gene expression, reduced hepatic nuclear factor-κB activities and levels of thiobarbituric acid reactive substances (TBARS) and restored mitochondrial oxidative metabolism and biogenesis. The results from the present sudy show that curcumin prevents fatty liver disease through multiple mechanisms, and suggest that curcumin may be used to prevent the development and progression of non-alcoholic fatty liver disease (NAFLD).

Topics: Adipose Tissue; Animals; Body Weight; Curcumin; Cytokines; Fatty Liver; Gene Expression Regulation; Inflammation; Inflammation Mediators; Male; Mice; Mice, Inbred C57BL; Mice, Obese; Mitochondria; Non-alcoholic Fatty Liver Disease; Obesity; Signal Transduction

Clinical and experimental evidence have demonstrated that alcohol consumption during pregnancy can disrupt brain development, leading to a variety of behavioral alterations including hyperactivity, motor dysfunction, and cognitive deficits in offsprings. Alcohol-induced neurocognitive deficits are associated with activation of oxidative-inflammatory cascade coupled with extensive apoptotic neurodegeneration in different brain regions.. The present study was designed with an aim to investigate the protective effect of curcumin, a principal curcuminoid present in the Indian spice turmeric, against alcohol-induced cognitive deficits, neuroinflammation, and neuronal apoptosis in rat pups postnatally exposed to ethanol.. Male Wistar rat pups were administered ethanol (5 g/kg, 12 % v/v) by intragastric intubation on postnatal days (PD) 7, 8, and 9 and were treated with curcumin (30 and 60 mg/kg) from PD 6 to 28. Performance of ethanol-exposed pups that did not receive curcumin was significantly impaired as evaluated in both Morris water maze and elevated plus maze tasks recorded by using computer tracking. Cognitive deficit was associated with enhanced acetylcholinesterase activity, increased neuroinflammation (oxidative-nitrosative stress, TNF-α, IL-1β, and TGF-β1), and neuronal apoptosis (NF-κβ and caspase 3) in both cerebral cortex and hippocampus of ethanol-exposed pups. Chronic treatment with curcumin significantly ameliorated all the behavioral, biochemical, and molecular alterations in different brain regions of ethanol-exposed pups.. The current study demonstrates the possible involvement of oxidative-inflammatory cascade-mediated apoptotic signaling in cognitive deficits associated with postnatal ethanol exposure and points towards the neuroprotective potential of curcumin in mitigating alcohol-induced behavioral, biochemical, and molecular deficits.

Topics: Acetylcholinesterase; Animals; Apoptosis; Cerebral Cortex; Cognition Disorders; Curcumin; Disease Models, Animal; Dose-Response Relationship, Drug; Ethanol; Hippocampus; Inflammation; Male; Maze Learning; Neurons; Oxidative Stress; Rats; Rats, Wistar

Wound healing is an intricate multistage process that includes inflammation, cell proliferation, matrix deposition and remodeling phases. It is often associated with oxidative stress and consequent prolonged inflammation, resulting in impaired wound healing. Curcumin has been reported to improve wound healing in different animal models. In order to increase the efficacy of curcumin in the healing arena a curcumin loaded oleic acid based polymeric (COP) bandage was formulated. The in vivo wound healing potency was compared with void bandage and control (cotton gauze treatment) in a rat model. Biochemical parameters and histological analysis revealed increased wound reduction and enhanced cell proliferation in COP bandage treated groups due to its efficient free radical scavenging properties. Comparative acceleration in wound healing was due to early implementation of fibroblasts and its differentiation (increased level of α-smooth muscle actin). Western blotting and semiquantitative PCR analysis clearly indicate that COP bandage can efficiently quench free radicals leading to reduced antioxidative enzyme activity. Further evidence at mRNA and protein level indicates that our system is potent enough to reduce the inflammatory response mediated by the NFκB pathway during wound healing. With this background, we anticipate that such a versatile approach may seed new arena for topical wound healing in the near future.

Topics: Aldehydes; Animals; Antioxidants; Bandages; Chemistry, Pharmaceutical; Collagen; Curcumin; Fibroblasts; Free Radical Scavengers; Free Radicals; Inflammation; Lipid Peroxidation; Male; NF-kappa B; Oleic Acid; Phosphatidylinositol 3-Kinases; Polymers; Proto-Oncogene Proteins c-akt; Rats; Rats, Sprague-Dawley; RNA, Messenger; Wound Healing

Diabetic cardiomyopathy (DCM), characterized by myocardial structural and functional changes, is an independent cardiomyopathy that develops in diabetic individuals. The present study was sought to investigate the effect of curcumin on modulating DCM and the mechanisms involved.. An experimental diabetic rat model was induced by low dose of streptozoticin(STZ) combined with high energy intake on rats. Curcumin was orally administrated at a dose of 100 or 200 mg · kg(-1) · d(-1), respectively. Cardiac function was evaluated by serial echocardiography. Myocardial ultrastructure, fibrosis area and apoptosis were assessed by histopathologic analyses. Metabolic profiles, myocardial enzymes and oxidative stress were examined by biochemical tests. Inflammatory factors were detected by ELISA, and interrelated proteins were measured by western blot.. Rats with DCM showed declined systolic myocardial performance associated with myocardial hypertrophy and fibrosis, which were accompanied with metabolism abnormalities, aberrant myocardial enzymes, increased AGEs (advanced glycation end products) accumulation and RAGE (receptor for AGEs) expression, elevated markers of oxidative stress (MDA, SOD, the ratio of NADP(+)/NADPH, Rac1 activity, NADPH oxidase subunits expression of gp91(phox) and p47(phox) ), raised inflammatory factor (TNF-α and IL-1β), enhanced apoptotic cell death (ratio of bax/bcl-2, caspase-3 activity and TUNEL), diminished Akt and GSK-3β phosphorylation. Remarkably, curcumin attenuated myocardial dysfunction, cardiac fibrosis, AGEs accumulation, oxidative stress, inflammation and apoptosis in the heart of diabetic rats. The inhibited phosphorylation of Akt and GSK-3β was also restored by curcumin treatment.. Taken together, these results suggest that curcumin may have great therapeutic potential in the treatment of DCM, and perhaps other cardiovascular disorders, by attenuating fibrosis, oxidative stress, inflammation and cell death. Furthermore, Akt/GSK-3β signaling pathway may be involved in mediating these effects.

Topics: Animals; Apoptosis; Cell Death; Curcumin; Diabetes Mellitus, Experimental; Diabetic Cardiomyopathies; Fibrosis; Glycogen Synthase Kinase 3; Glycogen Synthase Kinase 3 beta; Heart; Inflammation; Male; Myocardium; Oxidative Stress; Phosphorylation; Proto-Oncogene Proteins c-akt; Rats; Rats, Wistar; Receptor for Advanced Glycation End Products; Receptors, Immunologic; Ventricular Dysfunction, Left

In the present study, post-treatment effects of dietary turmeric on markers related to apoptosis, cell proliferation, and inflammation in 7,12-dimethylbenz(a)anthracene (DMBA)-induced hamster buccal pouch (HBP) tumors were investigated. Tumors were induced by applying 0.5% DMBA topically to the HBP three times per week for 12 weeks. After tumor development, half of the animals continued on the control diet and the other half were shifted to a 1% turmeric diet for 4 weeks. To rule out DMBA discontinuation as a cause of inhibition in tumor growth, DMBA treatment was continued during dietary exposure of turmeric in another set of animals until the end of the experiment. The turmeric diet inhibited tumor growth in animals with or without DMBA carcinogen treatment compared to the animals on the control diet. When compared to hamsters bearing tumors that remained on the control diet, the buccal pouches of hamsters bearing tumors receiving turmeric showed the following results: (1) decreased cell proliferation (diminished PCNA, cyclin D1, and Bcl-2) and PCNA labelling index, (2) enhanced apoptosis (increased Bax, caspase-3, caspase-9, and cytochrome c, and decreased survivin) and apoptotic index, (3) decreased inflammation (decreased Cox-2), and (4) decreased MAPK activation (p-ERK and p-p38). These data indicate that tumor growth decreased due to the modulation of cellular pathways associated with cell proliferation and apoptosis.

Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Apoptosis; Cell Proliferation; Cheek; Cricetinae; Curcuma; Curcumin; Inflammation; Male; Mesocricetus; Mouth Neoplasms; NF-kappa B; Phytotherapy

The anti-inflammatory effects of curcuminoids have been extensively investigated. However, few studies investigate the mechanistic involvement of microRNAs (miRNAs) in their activity. The objective of this study was to examine the protective effects of standardized curcuminoid extract (SCE) in vascular inflammation of human umbilical vein endothelial cells (HUVEC) and the potential involvement of miRNA-126 and miRNA-146a. Escherichia coli lipopolysacharides (LPS) were used to induce inflammation. LPS-challenge increased gene-expression of toll-like receptor-4 (TLR-4) and downstream genes IL-1 receptor-associated kinase 1 (IRAK-1) and tumor necrosis factor receptor-associated factor 6 (TRAF-6) up to 2.58-, 2.39-, and 3.73-fold, respectively, relative to DMSO-treated controls that were not challenged with LPS. LPS up-regulated TLR-4, IRAK-1, and TRAF-6 in SCE pretreated cells (5 mg L(-1)), only up to 0.69-, 1.28-, and 1.15-fold, respectively. miRNA-146a can be up-regulated by transcription nuclear factor kappa B (NF-κB) and acts as a negative feedback loop regulator involving IRAK-1 and TRAF-6 downregulation. In this study, the down-regulation of NF-κB was accompanied by reduced miRNA-146a expression. LPS-challenge induced mRNA levels of vascular cell adhesion molecule-1 (VCAM-1) and intracellular cell adhesion molecule-1 (ICAM-1) up to 5.65- and 10.65-fold, respectively. SCE prevented this effect and increases of up to only 2.92- and 5.26-fold of DMSO-treated controls not challenged with LPS were observed. miRNA-126 regulates endothelial expression of VCAM-1, but was not inversely correlated to the expression of its target gene VCAM-1 upon SCE treatment; therefore, miRNA-126 does not appear to be involved in the down-regulation of VCAM-1. Overall, curcuminoids are confirmed to have anti-inflammatory properties in HUVEC; however, neither miRNA-146a nor miRNA-126 seem to be involved in the SCE-induced down-regulation of the NF-κB-target genes IRAK-1, TRAF-6, and VCAM-1.

Topics: Anti-Inflammatory Agents; Curcuma; Escherichia coli; Gene Expression; Human Umbilical Vein Endothelial Cells; Humans; Inflammation; Interleukin-1 Receptor-Associated Kinases; Lipopolysaccharides; MicroRNAs; NF-kappa B; Plant Extracts; TNF Receptor-Associated Factor 6; Toll-Like Receptor 4

Curcuma has long been used as an anti-inflammatory agent in inflammatory bowel disease. Since gastrointestinal motility is impaired in inflammatory states, the aim of this work was to evaluate if Curcuma Longa had any effect on intestinal motility.. The biological activity of Curcuma extract was evaluated against Carbachol induced contraction in isolated mice intestine. Acute and chronic colitis were induced in Balb/c mice by Dextran Sulphate Sodium administration (5% and 2.5% respectively) and either Curcuma extract (200 mg/kg/day) or placebo was thereafter administered for 7 and 21 days respectively. Spontaneous contractions and the response to Carbachol and Atropine of ileum and colon were studied after colitis induction and Curcuma administration.. Curcuma extract reduced the spontaneous contractions in the ileum and colon; the maximal response to Carbachol was inhibited in a non-competitive and reversible manner. Similar results were obtained in ileum and colon from Curcuma fed mice. DSS administration decreased the motility, mainly in the colon and Curcuma almost restored both the spontaneous contractions and the response to Carbachol after 14 days assumption, compared to standard diet, but a prolonged assumption of Curcuma decreased the spontaneous and Carbachol-induced contractions.. Curcuma extract has a direct and indirect myorelaxant effect on mouse ileum and colon, independent of the anti-inflammatory effect. The indirect effect is reversible and non-competitive with the cholinergic agent. These results suggest the use of curcuma extract as a spasmolytic agent.

Topics: Animals; Anti-Arrhythmia Agents; Anti-Inflammatory Agents; Atropine; Carbachol; Cardiotonic Agents; Colitis; Colon; Curcuma; Ileum; Inflammation; Intestines; Male; Mice; Mice, Inbred BALB C; Muscle Relaxants, Central; Plant Extracts

The aim of this work was to determine the bioavailability of herbs and spices after human consumption by measuring the ability to protect lymphocytes from an oxidative injury and by examining the impact on inflammatory biomarkers in activated THP-1 cells.. Ten to 12 subjects in each of 13 groups consumed a defined amount of herb or spice for 7 days. Blood was drawn from subjects before consumption and 1 hour after taking the final herb or spice capsules. Subject serum and various extractions of the herbs and spices were analyzed for antioxidant capacity by oxygen radical absorbance capacity (ORAC) analysis or by 1,1-diphenyl-2-picrylhydrzyl (DPPH). Subject peripheral blood mononuclear cells (PBMCs) in medium with10% autologous serum were incubated with hydrogen peroxide to induce DNA strand breaks. Subject serum was also used to treat activated THP-1 cells to determine relative quantities of 3 inflammatory cytokine (tumor necrosis factor-α [TNF-α], interleukin-1α [IL-1α], and IL-6) mRNAs.. Herbs and spices that protected PBMCs against DNA strand breaks were paprika, rosemary, ginger, heat-treated turmeric, sage, and cumin. Paprika also appeared to protect cells from normal apoptotic processes. Of the 3 cytokine mRNAs studied (TNF-α, IL-1α, and IL-6), TNF-α was the most sensitive responder to oxidized LDL-treated macrophages. Clove, ginger, rosemary, and turmeric were able to significantly reduce oxidized LDL-induced expression of TNF-α. Serum from those consuming ginger reduced all three inflammatory biomarkers. Ginger, rosemary, and turmeric showed protective capacity by both oxidative protection and inflammation measures.. DNA strand breaks and inflammatory biomarkers are a good functional measure of a food's bioavailability.

Topics: Adult; Antioxidants; Biological Availability; Biomarkers; Cells, Cultured; Cinnamomum zeylanicum; Curcuma; DNA Breaks; Female; Humans; Inflammation; Interleukin-1alpha; Interleukin-6; Leukocytes, Mononuclear; Lipoproteins, LDL; Male; Oxidative Stress; Plant Extracts; Plants, Medicinal; Real-Time Polymerase Chain Reaction; RNA, Messenger; Rosmarinus; Spices; Syzygium; Tumor Necrosis Factor-alpha; Young Adult; Zingiber officinale

Curcumin, a polyphenol compound from Curcuma longa L. has been used for centuries as an anti-inflammatory remedy including asthma. Curcumin has been reported to exert an anti-inflammatory effect, in part, through inhibition of the NF-κB pathway.. The purposes of this study were to determine whether curcumin inhibits NF-κB-dependent transcription in vitro, and test whether treatment with curcumin reduces allergen-induced airway inflammation and hyper-responsiveness in a mouse model of asthma through inhibition of NF-κB pathway.. The effect of curcumin on NF-κB transcriptional activity was investigated using a cell-based luciferase reporter assay in A549 cells and by measuring inhibitory κBα (IκBα), p65, and p50 levels after exposure of Raw264.7 cells to lipopolysaccharide (LPS). BALB/c mice were sensitized to ovalbumin (OVA) by intraperitoneal injection, and challenged with repeated exposure to aerosolized OVA. The effects of daily administered curcumin (200mg/kg body weight, i.p.) on airway hyper-responsiveness (AHR), inflammatory cell number, and IgE levels in bronchoalveolar lavage (BAL) fluid were analyzed. NF-κB activation in lung tissue was also assessed by Western blot analyses.. Curcumin inhibited NF-κB-dependent transcription in reporter assays in A549 cells with an IC(50) of 21.50±1.25μM. Curcumin stabilized IκBα and inhibited nuclear translocation of p65 and p50 in LPS-activated Raw264.7 cells, and curcumin-treated mice showed reduced nuclear translocation of p65 in lung tissue. Treatment with curcumin significantly attenuated AHR and reduced the numbers of total leukocytes and eosinophils in BAL fluid. Infiltration of inflammatory cells and mucus occlusions in lung tissue were significantly ameliorated by treatment with curcumin, which also markedly decreased the level of IgE in BAL fluid.. Curcumin attenuates the development of allergic airway inflammation and hyper-responsiveness, possibly through inhibition of NF-κB activation in the asthmatic lung tissue. Our results indicate that curcumin may attenuate development of asthma by inhibition of NF-κB activation.

Topics: Animals; Anti-Inflammatory Agents; Asthma; Biological Transport; Bronchoalveolar Lavage Fluid; Cell Line; Curcuma; Curcumin; Eosinophils; Female; I-kappa B Proteins; Immunoglobulin E; Inflammation; Inhibitory Concentration 50; Leukocytes; Lung; Mice; Mice, Inbred BALB C; Mucus; NF-kappa B; NF-KappaB Inhibitor alpha; Phytotherapy; Plant Extracts; Rhizome; Transcription Factor RelA

Cholangiocarcinoma (CCA) is a highly metastatic tumor linked to liver fluke infection and consumption of nitrosamine-contaminated foods and is a major health problem especially in South-Eastern Asia. In search for a suitable chemopreventive agents, we investigated the effect of curcumin, a traditional anti-inflammatory agent derived from turmeric (Curcuma longa), on CCA development in an animal model by infection with the liver fluke Opisthorchis viverrini and administration of N-nitrosodimethylamine and fed with curcumin-supplemented diet. The effect of curcumin-supplemented diet on histopathological changes and survival were assessed in relation to NF-κB activation, and the expression of NF-κB-related gene products involved in inflammation, DNA damage, apoptosis, cell proliferation, angiogenesis and metastasis. Our results showed that dietary administration of this nutraceutical significantly reduced the incidence of CCA and increased the survival of animals. This correlated with the suppression of the activation of transcription factors including NF-κB, AP-1 and STAT-3, and reduction in the expression of proinflammatory proteins such as COX-2 and iNOS. The formation of iNOS-dependent DNA lesions (8-nitroguanine and 8-oxo-7,8-dihydro-2'-deoxyguanosine) was inhibited. Curcumin suppressed the expression of proteins related to cell survival (bcl-2 and bcl-xL), proliferation (cyclin D1 and c-myc), tumor invasion (MMP-9 and ICAM-1) and angiogenesis (VEGF), and microvessel density. Induction of apoptotic events as indicated by caspase activation and PARP cleavage was also noted. Our results suggest that curcumin exhibits an anticarcinogenic potential via suppression of various events involved in multiple steps of carcinogenesis, which is accounted for by its ability to suppress proinflammatory pathways.

Topics: Animals; Anticarcinogenic Agents; Apoptosis; Base Sequence; Cell Proliferation; Cell Transformation, Neoplastic; Cholangiocarcinoma; Cricetinae; Curcumin; Deoxyribonucleotides; Diet; Electrophoretic Mobility Shift Assay; Immunohistochemistry; Inflammation; Male; Mesocricetus; NF-kappa B

Curcumin's benefits on tumorigenesis are thought to be mediated by its antiinflammatory activity; however, these effects have not been well characterized in a mouse model of colon cancer. We examined the effects of curcumin on intestinal inflammation in the Apc(Min/+) mouse. Apc(Min/+) mice were given a placebo or curcumin (2%) diet from 4 to 18 weeks of age (n = 10/group). C57BL/6 mice were used as a wild-type control (n = 10/group). Intestines were analyzed for polyp burden (sections 1, 4, and 5) and for mRNA expression, and concentration of interleukin (IL)-1β, IL-6, tumor necrosis factor-α, and chemokine ligand 2 (CCL2) (sections 2 and 3). Plasma was collected for concentration of CCL2. Curcumin decreased total intestinal polyps by 75% (P < 0.05) in all size categories [>2 mm (65%), 1-2 mm (72%), <1 mm (82%); P < 0.05]. mRNA expression of IL-1β, IL-6, tumor necrosis factor-α, and CCL2 was elevated (P < 0.05) and curcumin blunted this increase (P < 0.05). Protein concentration of IL-1β, IL-6 (section 3), and CCL2 was increased (P < 0.05) and curcumin reduced this response for IL-1β (section 2) and CCL2 (P < 0.05). Curcumin also offset the increase in plasma CCL2 (P < 0.05). The benefits of curcumin in colon cancer may be at least in part mediated by its antiinflammatory activity.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Body Weight; Curcumin; Cytokines; Diet; Female; Inflammation; Intestinal Mucosa; Intestines; Male; Mice; Mice, Inbred C57BL; Neoplasms; Random Allocation

Long-term treatment with haloperidol is associated with a number of extrapyramidal side effects, particularly the irregular movements of chorionic type. This limitation presents a marked therapeutic challenge. The present study investigates the molecular etiology of haloperidol neurotoxicity and the role of curcumin, a well-known anti-oxidant, in ameliorating these adverse effects. The redox status of haloperidol-treated brains along with NO, TNF-α, NF-kappaB p65 subunit, caspase-3, and monoamine neurotransmitters were measured in the striatum of rat brain. Chronic treatment with haloperidol (5 mg/kg, i.p., 21 days) produced orofacial dyskinetic movements which were coupled with marked increase in oxidative stress parameters, TNF-α, caspase-3 activity in cytoplasmic lysate and active p65 sub unit of NF-kappaB in nuclear lysates of the striatum. Neurochemically, chronic administration of haloperidol resulted in a significant decrease in the levels of norepinephrine, dopamine, and serotonin. The prototype atypical anti-psychotic, clozapine (10 mg/kg, i.p., 21 days) produced mild oxidative stress but did not alter any other parameters. Interestingly, co-administration of curcumin (25 and 50 mg/kg, i.p., 21 days) dose-dependently prevented all the behavioral, cellular, and neurochemical changes associated with the chronic administration of haloperidol. Curcumin per se (50 mg/kg) did not show any side effects. Co-administration of piperine significantly enhanced the effect of curcumin (25 mg/kg) but not of curcumin (50 mg/kg). Collectively, the data indicated the potential of curcumin as an adjunct to haloperidol treatment and provided initial clues to the underlying molecular mechanisms in haloperidol neurotoxicity. This study also provides a rationale for the combination of piperine and curcumin.

Topics: Alkaloids; Analysis of Variance; Animals; Apoptosis; Behavior, Animal; Benzodioxoles; Caspase 3; Colorimetry; Curcumin; Cytokines; Disease Models, Animal; Dopamine Antagonists; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Enzyme-Linked Immunosorbent Assay; Haloperidol; Inflammation; Male; Neuroprotective Agents; Neurotoxicity Syndromes; Neurotransmitter Agents; Piperidines; Polyunsaturated Alkamides; Rats; Rats, Wistar; Statistics as Topic; Thiobarbituric Acid Reactive Substances

Current therapy-regimens against Helicobacter pylori (Hp) infections have considerable failure rates and adverse side effects that urge the quest for an effective alternative therapy. We have shown that curcumin is capable of eradicating Hp-infection in mice. Here we examine the mechanism by which curcumin protects Hp infection in cultured cells and mice. Since, MMP-3 and -9 are inflammatory molecules associated to the pathogenesis of Hp-infection, we investigated the role of curcumin on inflammatory MMPs as well as proinflammatory molecules. Curcumin dose dependently suppressed MMP-3 and -9 expression in Hp infected human gastric epithelial (AGS) cells. Consistently, Hp-eradication by curcumin-therapy involved significant downregulation of MMP-3 and -9 activities and expression in both cytotoxic associated gene (cag)(+ve) and cag(-ve) Hp-infected mouse gastric tissues. Moreover, we demonstrate that the conventional triple therapy (TT) alleviated MMP-3 and -9 activities less efficiently than curcumin and curcumin's action on MMPs was linked to decreased pro-inflammatory molecules and activator protein-1 activation in Hp-infected gastric tissues. Although both curcumin and TT were associated with MMP-3 and -9 downregulation during Hp-eradication, but unlike TT, curcumin enhanced peroxisome proliferator-activated receptor-γ and inhibitor of kappa B-α. These data indicate that curcumin-mediated healing of Hp-infection involves regulation of MMP-3 and -9 activities.

Topics: Animals; Cells, Cultured; Curcumin; Down-Regulation; Enzyme Inhibitors; Helicobacter Infections; Humans; Inflammation; Inflammation Mediators; Matrix Metalloproteinase 3; Matrix Metalloproteinase 9; Mice; Stomach

Nutritional compounds that potentially limit inflammation and tissue factor expression may decrease the progression of chronic kidney disease (CKD) and associated cardiovascular disease. This project aimed to determine the effect of curcumin, bovine colostrum, and fish oil on inflammatory cytokine and tissue factor procoagulant activity of peripheral blood mononuclear cells (PBMCs) from patients with CKD before dialysis.. Peripheral blood mononuclear cells from patients with CKD before dialysis (n = 13) and age- and sex-matched healthy controls (n = 12) were cultured alone and with low and high doses of the nutritional compounds for 24 h. Cells were cultured with and without lipopolysaccharide. Supernatants were analyzed for tumor necrosis factor-α, interleukin (IL)-6, IL-8, monocyte chemoattractant protein-1, IL-1β, C-reactive protein, and tissue factor procoagulant activity.. The production of C-reactive protein, monocyte chemoattractant protein-1, IL-6, and IL-1β by PBMCs was inhibited by low- and high-dose fish oil in the CKD group (P < 0.05). Curcumin decreased secretion of IL-6 (P = 0.015) and IL-1 β (P = 0.016). Curcumin was more effective than colostrum at decreasing the procoagulant activity of PBMCs in the CKD and control groups (P < 0.019).. Fish oil decreased inflammatory cytokine secretion from CKD PBMCs. In addition, the beneficial effects of curcumin were demonstrated in decreasing inflammation in vitro, often to a similar magnitude as fish oil.

Topics: Adult; Animals; Anti-Inflammatory Agents; C-Reactive Protein; Case-Control Studies; Cattle; Chemokine CCL2; Colostrum; Curcuma; Curcumin; Female; Fish Oils; Humans; Inflammation; Inflammation Mediators; Interleukin-1beta; Interleukin-6; Kidney Failure, Chronic; Leukocytes, Mononuclear; Lipopolysaccharides; Male; Middle Aged; Phytotherapy; Thromboplastin

Curcumin is a plant-derived dietary spice with various biological activities, including anticarcinogenic and anti-inflammatory effects. Its therapeutic applications have been studied in a variety of conditions, including rheumatoid arthritis, colon cancer and depression, but no studies have evaluated the effects of curcumin on periodontal disease in vivo.. Experimental periodontal disease was induced in rats by placing cotton ligatures around both lower first molars. Curcumin was given to the rats by the intragastric route daily at two dosages (30 and 100 mg/kg) for 15 d. Control animals received ligatures but only the corn oil vehicle by gavage, and no treatment-negative control animals were included. Bone resorption was assessed by micro-computed tomography, and the inflammatory status was evaluated by stereometric analysis. Both RT-qPCR and ELISA were used to determine the expression of interleukin-6, tumor necrosis factor-α and prostaglandin E(2) synthase in the gingival tissues. Modulation of p38 MAPK and nuclear factor-κB activation were assessed by western blotting.. Bone resorption was effectively induced in the experimental period, but it was not affected by either dose of curcumin. Curcumin effectively inhibited cytokine gene expression at both the mRNA and the protein level and produced a dose-dependent inhibition of the activation of nuclear factor-κB in the gingival tissues. Activation of p38 MAPK was not inhibited by curcumin. Curcumin-treated animals also presented a marked reduction of the inflammatory cell infiltrate and increased collagen content and fibroblastic cell numbers.. Curcumin did not prevent alveolar bone resorption, but its potent anti-inflammatory effect suggests that it may have a therapeutic potential in periodontal diseases.

Topics: Alveolar Bone Loss; Alveolar Process; Animals; Anti-Inflammatory Agents, Non-Steroidal; Cell Count; Collagen; Curcumin; Cyclooxygenase 2; Dose-Response Relationship, Drug; Fibroblasts; Gingiva; Image Processing, Computer-Assisted; Imaging, Three-Dimensional; Inflammation; Interleukin-6; Intramolecular Oxidoreductases; Male; NF-kappa B; p38 Mitogen-Activated Protein Kinases; Periodontitis; Prostaglandin-E Synthases; Random Allocation; Rats; Rats, Sprague-Dawley; Tumor Necrosis Factor-alpha; X-Ray Microtomography

Therapeutic utility of bone marrow transplantation in diabetes is an attractive approach. However, the oxidative stress generated by hyperglycemia may hinder β-cell regeneration. The present study was undertaken to investigate the therapeutic potential of curcumin, a dietary spice with antioxidant activity, bone marrow transplantation, and their combined effects in the reversal of experimental diabetes. Diabetes was induced in mice by multiple low doses of streptozotocin. After the onset of diabetes, mice were treated with curcumin (10 mM; 100 μl/mouse, i.p., for 28 days) or received a single bone marrow transplantation (10(6) un-fractionated bone marrow cells), or both. Parameters of diabetes, integrity of pancreatic islets, pancreatic oxidative stress markers, and serum pro-inflammatory cytokines, were evaluated. Treatment with either curcumin or bone marrow transplantation significantly reversed streptozotocin-induced hyperglycemia/glucose intolerance, hypoinsulinemia, and damage of pancreatic islets. Interestingly, combination of curcumin and bone marrow transplantation elicited the most profound alleviation of such streptozotocin-evoked anomalies; including islet regeneration/insulin secretion. On the other hand, curcumin, either alone or combined with bone marrow transplantation, blunted the pancreatic lipid-peroxidation, up-regulated activities of the antioxidant enzymes, and suppressed serum levels of TNF-α and IL-1β. Curcumin and single bone marrow transplantation proved their therapeutic potential in reversing diabetes when used in combination. Curcumin, via its antioxidant and anti-inflammatory effects, evidently enhanced the ability of bone marrow transplantation to regenerate functional pancreatic islets. Hence, the use of natural antioxidants combined with other therapeutic regimens to induce pancreatic regeneration is a promising strategy in the management of diabetes.

Topics: Animals; Antioxidants; Blood Glucose; Body Weight; Bone Marrow Cells; Bone Marrow Transplantation; Curcumin; Cytokines; Diabetes Mellitus, Experimental; Glucose Tolerance Test; Inflammation; Insulin; Insulin Secretion; Insulin-Secreting Cells; Interleukin-1beta; Islets of Langerhans; Lipid Peroxidation; Mice; Oxidative Stress; Regeneration; Tumor Necrosis Factor-alpha

Alzheimer's disease (AD) is a neurodegenerative disorder, which depicts features of chronic inflammatory conditions resulting in cellular death and has limited therapeutic options. We aimed to explore the effect of a curcuminoid mixture and its individual components on inflammatory and apoptotic genes expression in AD using an Aβ+ibotenic acid-infused rat model. After 5 days of treatment with demethoxycurcumin, hippocampal IL-1β levels were decreased to 118.54 ± 47.48 and 136.67 ± 31.96% respectively at 30 and 10mg/kg, compared with the amyloid treated group (373.99 ± 15.28%). After 5 days of treatment, the curcuminoid mixture and demethoxycurcumin effectively decreased GFAP levels in the hippocampus. When studied for their effect on apoptotic genes expression, the curcuminoid mixture and bisdemethoxycurcumin effectively decreased caspase-3 level in the hippocampus after 20 days of treatment, where bisdemethoxycurcumin showed a maximal rescuing effect (92.35 ± 3.07%) at 3mg/kg. The curcuminoid mixture at 30 mg/kg decreased hippocampal FasL level to 70.56 ± 3.36% after 5 days of treatment and 19.01 ± 2.03% after 20 days. In the case of Fas receptor levels, demethoxycurcumin decreased levels after 5 days of treatment with all three doses showing a maximal effect (189.76 ± 15.01%) at 10mg/kg. Each compound was effective after 20 days in reducing Fas receptor levels in the hippocampus. This study revealed the important effect of curcuminoids on genes expression, showing that, each component of the curcuminoid mixture distinctly affects gene expression, thus highlighting the therapeutic potential of curcuminoids in AD.

Topics: Alzheimer Disease; Amyloid beta-Peptides; Animals; Anti-Inflammatory Agents, Non-Steroidal; Apoptosis; bcl-2-Associated X Protein; Caspase 3; Curcumin; Cyclooxygenase 2; Disease Models, Animal; Excitatory Amino Acid Agonists; Fas Ligand Protein; fas Receptor; Frontal Lobe; Gene Expression Regulation; Glial Fibrillary Acidic Protein; Hippocampus; Ibotenic Acid; Inflammation; Interleukin-1beta; Male; Peptide Fragments; Proto-Oncogene Proteins c-bcl-2; Rats; Rats, Sprague-Dawley; Time Factors

Inflammatory processes play essential roles in the pathogenesis of tendinitis and tendinopathy. These events are accompanied by catabolic processes initiated by pro-inflammatory cytokines such as interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α). Pharmacological treatments for tendinitis are restricted to the use of non-steroidal anti-inflammatory drugs. Recent studies in various cell models have demonstrated that curcumin targets the NF-κB signaling pathway. However, its potential for the treatment of tendinitis has not been explored. Herein, we used an in vitro model of human tenocytes to study the mechanism of curcumin action on IL-1β-mediated inflammatory signaling. Curcumin at concentrations of 5-20 μm inhibited IL-1β-induced inflammation and apoptosis in cultures of human tenocytes. The anti-inflammatory effects of curcumin included down-regulation of gene products that mediate matrix degradation (matrix metalloproteinase-1, -9, and -13), prostanoid production (cyclooxygenase-2), apoptosis (Bax and activated caspase-3), and stimulation of cell survival (Bcl-2), all known to be regulated by NF-κB. Furthermore, curcumin suppressed IL-1β-induced NF-κB activation via inhibition of phosphorylation and degradation of inhibitor of κBα, inhibition of inhibitor of κB-kinase activity, and inhibition of nuclear translocation of NF-κB. Furthermore, the effects of IL-1β were abrogated by wortmannin, suggesting a role for the phosphatidylinositol 3-kinase (PI-3K) pathway in IL-1β signaling. Curcumin suppressed IL-1β-induced PI-3K p85/Akt activation and its association with IKK. These results demonstrate, for the first time, a potential role for curcumin in treating tendon inflammation through modulation of NF-κB signaling, which involves PI-3K/Akt and the tendon-specific transcription factor scleraxis in tenocytes.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Basic Helix-Loop-Helix Transcription Factors; bcl-2-Associated X Protein; Cell Survival; Cells, Cultured; Collagenases; Curcumin; Cyclooxygenase 2; Dose-Response Relationship, Drug; Humans; Inflammation; Interleukin-1beta; Male; Middle Aged; NF-kappa B; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Signal Transduction; Tendons; Tumor Necrosis Factor-alpha

Mango ginger (Curcuma amada Roxb.) is a unique spice having morphological resemblance with ginger but imparts a raw mango flavour. The main use of mango ginger rhizome is in the manufacture of pickles and culinary preparations. Ayurveda and Unani medicinal systems have given much importance to mango ginger as an appetizer, alexteric, antipyretic, aphrodisiac, diuretic, emollient, expectorant and laxative and to cure biliousness, itching, skin diseases, bronchitis, asthma, hiccough and inflammation due to injuries. The biological activities of mango ginger include antioxidant activity, antibacterial activity, antifungal activity, anti-inflammatory activity, platelet aggregation inhibitory activity, cytotoxicity, antiallergic activity, hypotriglyceridemic activity, brine-shrimp lethal activity, enterokinase inhibitory activity, CNS depressant and analgesic activity. The major chemical components include starch, phenolic acids, volatile oils, curcuminoids and terpenoids like difurocumenonol, amadannulen and amadaldehyde. This article brings to light the major active components present in C. amada along with their biological activities that may be important from the pharmacological point of view.

Topics: Analgesics; Anti-Allergic Agents; Anti-Bacterial Agents; Anti-Inflammatory Agents; Antiemetics; Antioxidants; Bacteria; Curcuma; Curcumin; Humans; Hydroxybenzoates; Hypersensitivity; Inflammation; Microbial Sensitivity Tests; Oils, Volatile; Pain; Plant Extracts; Rhizome; Skin Diseases; Terpenes

Curcumin (diferuloylmethane) shows significant activity across a wide spectrum of conditions, but its usefulness is rather limited because of its low bioavailability. Use of nanoparticle formulations to enhance curcumin bioavailability is an emerging area of research.. In the present study, curcumin-loaded apotransferrin nanoparticles (nano-curcumin) prepared by sol-oil chemistry and were characterized by electron and atomic force microscopy. Confocal studies and fluorimetric analysis revealed that these particles enter T cells through transferrin-mediated endocytosis. Nano-curcumin releases significant quantities of drug gradually over a fairly long period, ∼50% of curcumin still remaining at 6 h of time. In contrast, intracellular soluble curcumin (sol-curcumin) reaches a maximum at 2 h followed by its complete elimination by 4 h. While sol-curcumin (GI(50) = 15.6 µM) is twice more toxic than nano-curcumin (GI(50) = 32.5 µM), nano-curcumin (IC(50)<1.75 µM) shows a higher anti-HIV activity compared to sol-curcumin (IC(50) = 5.1 µM). Studies in vitro showed that nano-curcumin prominently inhibited the HIV-1 induced expression of Topo II α, IL-1β and COX-2, an effect not seen with sol-curcumin. Nano-curcumin did not affect the expression of Topoisomerase II β and TNF α. This point out that nano-curcumin affects the HIV-1 induced inflammatory responses through pathways downstream or independent of TNF α. Furthermore, nano-curcumin completely blocks the synthesis of viral cDNA in the gag region suggesting that the nano-curcumin mediated inhibition of HIV-1 replication is targeted to viral cDNA synthesis.. Curcumin-loaded apotransferrin nanoparticles are highly efficacious inhibitors of HIV-1 replication in vitro and promise a high potential for clinical usefulness.

Topics: Antigens, Neoplasm; Apoproteins; Cell Death; Cell Line; Curcumin; DNA Topoisomerases, Type II; DNA-Binding Proteins; DNA, Viral; Drug Delivery Systems; HIV-1; Humans; Inflammation; Leukocytes, Mononuclear; Nanoparticles; Neutralization Tests; Particle Size; Receptors, Transferrin; Transferrin; Virus Replication

Topics: Anti-Inflammatory Agents, Non-Steroidal; Antineoplastic Agents; Antioxidants; Chronic Disease; Clinical Trials as Topic; Contraindications; Curcumin; Herb-Drug Interactions; Humans; Inflammation; Medicine, Ayurvedic; Neoplasms; Plants, Medicinal

Currently, the major drug discovery paradigm for neurodegenerative diseases is based upon high affinity ligands for single disease-specific targets. For Alzheimer's disease (AD), the focus is the amyloid beta peptide (Aß) that mediates familial Alzheimer's disease pathology. However, given that age is the greatest risk factor for AD, we explored an alternative drug discovery scheme that is based upon efficacy in multiple cell culture models of age-associated pathologies rather than exclusively amyloid metabolism. Using this approach, we identified an exceptionally potent, orally active, neurotrophic molecule that facilitates memory in normal rodents, and prevents the loss of synaptic proteins and cognitive decline in a transgenic AD mouse model.

Topics: Alzheimer Disease; Amyloid beta-Peptides; Animals; Behavior, Animal; Brain-Derived Neurotrophic Factor; Cognition; Curcumin; Disease Models, Animal; Heat-Shock Proteins; Hippocampus; Humans; Immunohistochemistry; Inflammation; Long-Term Potentiation; Memory; Mice; Nerve Growth Factors; Neuroprotective Agents; Oxidants; Oxidative Stress; Phosphorylation; Pyrazoles; Rats; Solubility; Structure-Activity Relationship; Synapses; Up-Regulation

Curcuma longa (turmeric) has a long history of use in Ayurvedic medicine as a treatment for inflammatory conditions. The purpose of the present study was to investigate the preventive effects of curcumin against acute pancreatitis (AP) induced by caerulein in mouse and to elucidate possible mechanism of curcumin action.. Curcumin (50 mg/kg/day) was intraperitoneally injected to Kun Ming male mice for 6 days, followed by injection of caerulein to induce AP. GW9662 (0.3 mg/kg), a specific peroxisome proliferator-activated receptor gamma (PPARγ) antagonist, was intravenously injected along with curcumin. Murine macrophage RAW264.7 cells were treated with 100 μmol/l curcumin for 2 h, and then stimulated with 0.1 μ g/ml lipopolysaccharide (LPS). Serum amylase and transaminase levels were measured at 10 h after AP. TNF-α level in mouse serum and cell culture medium were detected by ELISA. Expression of PPARγ and NF-κB were analyzed by RT-PCR and Western blot.. Curcumin significantly decreased the pancreas injury and reversed the elevation of serum amylase, ALT and AST activities and TNF-α level in mice with AP. Curcumin treatment inhibited the elevation of NF-κB-p65 in the nucleus of mouse pancreas AP group and RAW264.7 cells, but significantly increased the expression of PPARγ. GW9662 could abolish the effects of curcumin on serum levels of amylase, ALT, AST, TNF-α, and NF-κB level.. Our results suggest that curcumin could attenuate pancreas tissue and other organ injury by inhibiting the release of inflammatory cytokine TNF-α. These effects may involve upregulation of PPARγ and subsequent downregulation of NF-κB.

Topics: Alanine Transaminase; Amylases; Anilides; Animals; Cell Nucleus; Ceruletide; Curcuma; Curcumin; Disease Models, Animal; Gene Expression Regulation; Inflammation; Lipopolysaccharides; Macrophages; Male; Mice; NF-kappa B; Pancreatitis; Plant Extracts; PPAR gamma; Transaminases; Tumor Necrosis Factor-alpha

The present study revealed the indirect effect of a turmeric (TUR) diet on the histopathological changes and proliferating cell nuclear antigen staining in Syrian hamsters with partial obstruction by liver fluke (Opisthorchis viverrini) infection and inflammation by N-nitrosodimethylamine (NDMA) administration. The result of the analysis of histopathological changes shows that a TUR diet has an anti-inflammatory property in the case of a single condition of NDMA administration or O. viverrini infection, as has been reported previously. Unfortunately, an adverse indirect effect of TUR was observed in the combination of infection with O. viverrini and administration of NDMA, with a 30-50% increase in new bile duct formation, correlated with an increase in proliferating cell nuclear antigen. Our present result suggests that the properties of curcumin are anti-inflammation and antioxidant including enhancing biliary contraction and bile flow. Thus, a combination of factors (treated with O. viverrini, NDMA, and TUR diet) result in an increasing bile duct proliferation which may cause from biliary homeostasis.

Topics: Animals; Anti-Inflammatory Agents; Bile Ducts; Cholestasis; Cricetinae; Curcuma; Diet; Dimethylnitrosamine; Fasciola hepatica; Inflammation; Mesocricetus; Opisthorchiasis; Opisthorchis

The aim of this study was to investigate the effects of xanthorrhizol (5-(1,5-dimethyl-4-hexenyl)-2-methylphenol, XA) in a mouse model of dextran sulfate sodium (DSS)-induced colitis.. Experimental colitis was induced by exposing male BALB/c mice to 5% DSS in drinking water for 7days. XA (10 or 100mg/kg) was administered orally once a day, together with the DSS. We evaluated body weight, colon length, histological changes, and myeloperoxidase (MPO) activity. A cDNA microarray was used to assess the gene expression profiles that were affected by XA and DSS treatment and a co-citation analysis was used to examine the biological relationship between XA-responsive genes and colitis.. Decreased body weight, shortened colon length, and damaged colon were observed in the group that was exposed to DSS. Oral administration of XA (10 or 100mg/kg) rescued these symptomatic and histopathological features. The DSS-induced increase in MPO activity, which was used as an index of neutrophil infiltration, was significantly decreased after treatment with XA. Microarray analysis revealed that XA treatment regulated the expression of 34 genes that were altered by exposure to DSS, and that these XA-responsive genes were associated with colonic inflammation. Furthermore, co-citation analysis and graphing of XA-responsive genes revealed a network associated with the gene that encodes for MPO.. These results suggest that XA attenuates acute DSS-induced colitis, possibly by modulating the expression of genes mostly associated with colonic inflammation.

Topics: Animals; Colitis; Curcuma; Dextran Sulfate; Gene Expression Profiling; Gene Expression Regulation; Inflammation; Male; Mice; Mice, Inbred BALB C; Phenols; Plant Extracts

This protocol describes microsphere-based protease assays for use in flow cytometry and high-throughput screening. This platform measures a loss of fluorescence from the surface of a microsphere due to the cleavage of an attached fluorescent protease substrate by a suitable protease enzyme. The assay format can be adapted to any site or protein-specific protease of interest and results can be measured in both real time and as endpoint fluorescence assays on a flow cytometer. Endpoint assays are easily adapted to microplate format for flow cytometry high-throughput analysis and inhibitor screening.

Topics: Animals; Biotinylation; Flow Cytometry; Fluorescence Resonance Energy Transfer; Green Fluorescent Proteins; High-Throughput Screening Assays; Humans; Inflammation; Kinetics; Microspheres; Peptide Hydrolases; Peptides; Reproducibility of Results; Temperature

Curcumin is a nontoxic, hepatoprotective antioxidant. It has been shown to efficiently scavenge oxygen free radicals, increase intracellular glutathione concentrations, and prevent lipid peroxidation in rat hepatocytes. Moreover, it has strong anti-inflammatory effects. In the present study we assessed its effect in a model of liver regeneration impaired by bacterial infections.. Male Sprague-Dawley rats underwent sham operation, cecal ligation and puncture (CLP), synchronous partial hepatectomy (PH), and CLP or synchronous PH+CLP with perioperative application of curcumin (100 mg per kg bodyweight per d) 48 h before surgery. Rats were sacrificed 24 h after surgery. Liver function was analyzed by measuring the serum albumin, serum bilirubin, and bile production. The local inflammatory response in the liver tissue was evaluated by quantification of TNF-alpha, IL-6 mRNA, and quantification of IL-1beta by ELISA. In addition, hepatic concentrations of reduced glutathione (GSH) and the oxidized disulfide dimer of glutathione (GSSG) were measured for determination of the redox state.. After simultaneous PH+CLP curcumin significantly reduced the expression of TNF-alpha and IL-6 mRNA in the liver tissue. The IL-1beta concentration in the liver was also slightly, but not significantly, lower in the curcumin group. A severe depletion of hepatic glutathione was found in the PH+CLP group. This was reversed by curcumin application, after which the GSH to GSSG ratio increased markedly. The hepatocellular damage, measured by ALT liberation, was significantly lower in the curcumin treated group. The relative liver weight in the curcumin group was significantly higher 24 h after PH+CLP. However, hepatocellular proliferation parameters were not significantly improved by antioxidative treatment with curcumin. Only the Ki-67 index was slightly higher in the curcumin treated PH+CLP group (14+/-3%) than in the untreated PH+CLP group (7%+/-3%). The hepatocyte density was significantly lower in the curcumin group than in the corresponding untreated group.. In the present model, curcumin revealed significant hepatoprotective effects with stabilization of redox state, reduced liberation of liver enzymes, and attenuated expression of pro-inflammatory cytokines. However, the hepatocellular proliferation was not significantly influenced.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Bacterial Infections; Curcumin; Glutathione; Hepatectomy; Inflammation; Liver; Liver Function Tests; Liver Regeneration; Male; Oxidative Stress; Rats; Rats, Sprague-Dawley

Inflammatory response plays an important role not only in the normal physiology but also in the pathology such as cancers. As chronic inflammations are associated with malignancies, it is important to prevent inflammation-mediated neoplastic formation, promotion and/or progression. One possible intervention will be using cancer chemopreventive agents such as curcumin (CUR), a potent anti-inflammatory and anti-oxidative stress compound. Polyunsaturated fatty acids (PUFA) such as docosahexaenoic acid (DHA) or eicosapentaenoic acid (EPA) are potent anti-inflammatory agents by decreasing the production of inflammatory eicosanoids, cytokines, and reactive oxygen species (ROS). The present study aims at examining whether CUR with DHA or EPA would have synergistic anti-inflammatory effects in RAW 264.7 cells. Non-toxic concentrations of single and combination of the compounds were investigated at 6, 12 and 24h. The nitric oxide (NO) suppression effects were most prominent at 24h. All the combinations of CUR and DHA or EPA with lower concentrations of CUR 5 microM and 25 microM of DHA or EPA were found to have synergistic effects in suppressing LPS-stimulated NO and endogenous NO levels. Importantly, very low doses of CUR 2.5 microM and DHA or EPA of 0.78 microM could synergistically suppress the LPS-induced prostaglandin E(2) (PGE(2)). The combinations were also found to suppress iNOS, COX-2, 5-lipoxygenase (5-LOX) and cPLA(2) but induce HO-1. Taken together, the present study clearly shows the synergistic anti-inflammatory as well as anti-oxidative stress effects of CUR and PUFA.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Cell Line; Cell Survival; Curcumin; Docosahexaenoic Acids; Drug Synergism; Drug Therapy, Combination; Eicosapentaenoic Acid; Fatty Acids, Unsaturated; Inflammation; Mice

Curcumin is a highly pleiotropic molecule with significant regulatory effects upon inflammation and inflammatory related diseases. However curcumin has one major important limitation in which it has poor bioavailability. Design of synthetic structural derivatives of curcumin is but one approach that has been used to overcome its poor bioavailability while retaining, or further enhancing, its drug-like effects. We have synthesized a series of curcumin analogues and describe the effects of 2,6-bis-4-(hydroxyl-3-methoxy-benzylidine)-cyclohexanone or BHMC upon nitric oxide and cytokine synthesis in cellular models of inflammation. BHMC showed a significant dose-response inhibitory action upon the synthesis of NO and we have shown that this effect was due to suppression of both iNOS gene and enzyme expression without any effects upon scavenging of nitrite. We also demonstrated that BHMC has a very minimal effect upon iNOS activity with no effect at all upon the secretion of PGE(2) but has a strong inhibitory effect upon MCP-1 and IL-10 secretion and gene expression. Secretion and gene expression of TNF-alpha and IL-6 were moderately inhibited whereas IL-8 and IL-1beta were not altered. We conclude that BHMC selectively inhibits the synthesis of several inflammatory mediators. BHMC should be considered a promising drug lead for preclinical and further pharmacological studies.

Topics: Animals; Cell Line; Cell Survival; Chemokines; Curcumin; Cyclohexanones; Cytokines; Dose-Response Relationship, Drug; Gene Expression Regulation, Enzymologic; Humans; Inflammation; Mice; Nitric Oxide; Nitric Oxide Synthase Type II

Our previous report has showed that demethoxycurcumin (DMC), a natural derivative of curcumin (Cur), exhibited stronger inhibitory activity on nitric oxide (NO) and tumor necrosis factor-alpha (TNF-alpha) production compared with Cur in lipopolysaccharide (LPS) activated rat primary microglia. In the present study, the effect and possible mechanism of DMC on the production of pro-inflammatory mediators in LPS-activated N9 microglial cells were further investigated. The results showed that DMC significantly suppressed the NO production induced by LPS in N9 microglial cells through inhibiting the protein and mRNA expression of inducible NO synthase (iNOS). DMC also decreased LPS-induced TNF-alpha and IL-1beta expression at both transcriptional and protein level in a concentration-dependent manner. Further studies revealed that DMC blocked IkappaBalpha phosphorylation and degradation, inhibited the phosphorylation of mitogen-activated protein kinases (MAPKs). Moreover, the level of intracellular reactive oxygen species (iROS) was significantly increased by LPS, which is mainly mediated by the up-regulated expression of gp91phox, the catalytic subunit of nicotinamide adenine dinucleotide phosphate reduced (NADPH) oxidase. Both DMC and Cur could markedly decrease iROS production and the expression of NADPH oxidase induced by LPS, with more potent inhibitory activity of DMC. In summary, these data suggest that DMC exerts its in vitro anti-inflammatory effect in LPS-activated N9 microglial cells by blocking nuclear factor-kappaB (NF-kappaB) and MAPKs activation, which may be partly due to its potent down-regulation of the NADPH-derived iROS production.

Topics: Animals; Anti-Inflammatory Agents; Biphenyl Compounds; Blotting, Western; Cell Survival; Curcumin; Diarylheptanoids; Down-Regulation; Inflammation; Interleukin-1beta; Lipopolysaccharides; Macrophage Activation; Mice; Microglia; Mitogen-Activated Protein Kinases; NF-kappa B; Nitric Oxide; Nitric Oxide Synthase Type II; Nitrites; Picrates; Reactive Oxygen Species; Reverse Transcriptase Polymerase Chain Reaction; Signal Transduction; Tumor Necrosis Factor-alpha

Curcumin and saikosaponin A as antioxidants improve antioxidant status. This study investigated the anti-inflammatory and antifibrotic actions of curcumin and saikosaponin A on CCl(4)-induced liver damage. Sprague-Dawley rats were randomly divided into control, CCl(4), CCl(4)+ curcumin (0.005%; CU), CCl(4) + saikosaponin A (0.004%; SS), and CCl(4) + curcumin + saikosaponin A (0.005% + 0.004%; CU + SS) groups. Carbon tetrachloride (40% in olive oil) at a dose of 0.75 ml/kg was injected intraperitoneally once a week. Curcumin and saikosaponin A were supplemented alone or in combination with diet 1 week before CCl(4) injection for 8 weeks. After 8-week supplementation, histopathological results showed hepatic collagen deposition was significantly reduced in the CU and SS groups, and activated nuclear factor-kappa B expression induced by CCl(4) in the liver was significantly inhibited by curcumin and/or saikosaponin A. Hepatic proinflammatory cytokines tumor necrosis factor-alpha, interleukin-1beta, and interleukin-6 were significantly inhibited, and anti-inflammatory cytokine interleukin-10 was significantly increased by supplementation with curcumin and/or saikosaponin A. Additionally, curcumin and/or saikosaponin A significantly reduced the increased levels of hepatic transforming growth factor-beta1 and hydroxyproline after CCl(4) treatment. Therefore, supplementation with curcumin and/or saikosaponin A suppress inflammation and fibrogenesis in rats with CCl(4)-induced liver injury. However, the combination has no additive effects on anti-inflammation and antifibrosis.

Topics: Animals; Anti-Inflammatory Agents; Bupleurum; Carbon Tetrachloride; Chemical and Drug Induced Liver Injury; Collagen; Curcuma; Curcumin; Cytokines; Dietary Supplements; Drug Therapy, Combination; Fibrosis; Hydroxyproline; Inflammation; Liver; Male; NF-kappa B; Oleanolic Acid; Phytotherapy; Plant Extracts; Plant Roots; Random Allocation; Rats; Rats, Sprague-Dawley; Rhizome; Saponins; Transforming Growth Factor beta1

Curcumin, a component of turmeric (Curcuma longa), is known to exert a variety of biological functions including anti-inflammatory activity. We examined the inhibitory effects of chemically synthesized derivatives of curcumin against inflammatory responses and compared them with those of curcumin, in order to find derivatives with stronger effects than curcumin. In a cell culture system using the mouse macrophage cell line RAW264.7, monoacetylcurcumin strongly inhibited IkappaB phosphorylation, nuclear factor (NF)-kappaB activation and tumor necrosis factor (TNF)-alpha production induced by lipopolysaccharide (LPS). In addition, oral administration of monoacetylcurcumin to mice led to greater suppression of TNF-alpha production after LPS stimulation than the administration of curcumin or tetrahydrocurcumin in vivo. Monoacetylcurcumin also inhibited the LPS-induced NF-kappaB activation in the liver. Collectively, monoacetylcurcumin is a potential chemopreventive agent for treating inflammatory responses more effectively than curcumin.

Topics: Animals; Anti-Inflammatory Agents; Cell Line; Curcumin; Humans; Inflammation; Lipopolysaccharides; Macrophages; Male; Mice; Mice, Inbred C57BL; NF-kappa B; Reactive Oxygen Species; Tumor Necrosis Factor-alpha

Alzheimer's disease (AD) is the most common age-related neurodegenerative disorder. Accumulating data indicate that astrocytes play an important role in the neuroinflammation related to the pathogenesis of AD. It has been shown that microglia and astrocytes are activated in AD brain and amyloid-beta (Abeta) can increase the expression of cyclooxygenase 2 (COX-2), interleukin-1, and interleukin-6. Suppressing the inflammatory response caused by activated astrocytes may help to inhibit the development of AD. Curcumin is a major constituent of the yellow curry spice turmeric and proved to be a potential anti-inflammatory drug in arthritis and colitis. There is a low age-adjusted prevalence of AD in India, a country where turmeric powder is commonly used as a culinary compound. Curcumin has been shown to suppress activated astroglia in amyloid-beta protein precursor transgenic mice. The real mechanism by which curcumin inhibits activated astroglia is poorly understood. Here we report that the expression of COX-2 and glial fibrillary acidic protein were enhanced and that of peroxisome proliferator-activated receptor gamma (PPARgamma) was decreased in Abeta(25-35)-treated astrocytes. In line with these results, nuclear factor-kappaB translocation was increased in the presence of Abeta. All these can be reversed by the pretreatment of curcumin. Furthermore, GW9662, a PPARgamma antagonist, can abolish the anti-inflammatory effect of curcumin. These results show that curcumin might act as a PPARgamma agonist to inhibit the inflammation in Abeta-treated astrocytes.

Topics: Amyloid beta-Peptides; Anilides; Animals; Animals, Newborn; Astrocytes; Cells, Cultured; Curcumin; Cyclooxygenase 2; Glial Fibrillary Acidic Protein; Inflammation; Nerve Tissue Proteins; Nuclear Proteins; PPAR gamma; Rats; Rats, Sprague-Dawley

Chronic infection with the liver fluke, Opisthorchis viverrini, induces advanced periductal fibrosis and is a relative risk factor for cholangiocarcinoma in Southeastern Asia. We examined the reducing effect of curcumin on hepatobiliary fibrosis using O. viverrini-infected hamsters supplemented with dietary 1% curcumin (w/w) as an animal model. The expression profile of matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs), cytokines, and collagens was assessed in relation to liver fibrosis. Histopathological studies revealed that curcumin had no effect on fibrosis at the short-term infection (21 days and 1 month); however, peribiliary fibrosis was significantly reduced after the long-term curcumin treatment for 3 months, compared to the untreated group. Expression of alpha-smooth muscle actin was associated with the reduction of liver fibrosis. A decrease in hepatic hydroxyproline level and mRNA expression of collagen I and III supported the reduction of fibrosis. The expression of TIMP-1, TIMP-2, and tumor necrosis factor-alpha genes was also decreased after curcumin treatment. In contrast, curcumin increased mRNA expression of MMP-13, MMP-7 (at 6 months), interleukin-1 beta, and transforming growth factor beta, implying that increased MMPs activity contributes to extracellular matrix degradation. These results suggest that curcumin reduces periductal fibrosis after long-term treatment by tissue resorption via inhibition of TIMPs expression and enhancement of MMPs expression mediated by cytokines. In conclusion, curcumin may serve as a promising nutraceutical agent exerting antifibrotic effect in O. viverrini-infected patients and contribute to cholangiocarcinoma prevention.

Topics: Actins; Animals; Collagen; Cricetinae; Curcumin; Drug Administration Schedule; Gene Expression Regulation; Hydroxyproline; Inflammation; Interleukin-1beta; Liver Cirrhosis; Liver Cirrhosis, Experimental; Male; Matrix Metalloproteinases; Opisthorchiasis; Tissue Inhibitor of Metalloproteinase-1; Tissue Inhibitor of Metalloproteinase-2; Tissue Inhibitor of Metalloproteinases; Transforming Growth Factor beta; Tumor Necrosis Factor-alpha

We have identified a novel anti-inflammatory signaling pathway that leads to the expression of heme oxygenase-1 (HO-1) in response to bisdemethoxycurcumin (BDMC), an analog of curcumin. Treatment with BDMC suppressed inducible nitric oxide synthase expression and nitric oxide (NO) production by down-regulating NF-kappaB activity in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. These effects were reversed by blocking HO-1 activity or expression. The signaling pathway involved in BDMC-mediated HO-1 induction included Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) and extracellular signal-regulated kinase 1/2 (ERK1/2). BDMC induced phosphorylation of ERK1/2 in a CaMKII-dependent manner. Pretreatment with the mitogen-activated protein kinase kinase 1/2 (MEK1/2) inhibitor, U0126, inhibited CaMKII-induced stimulation of HO-1 promoter activity, suggesting that ERK1/2 is a downstream mediator of CaMKII in BDMC signaling to HO-1 expression. Furthermore, the CaMKII-ERK1/2 cascade targets the transcription factor, NF-E2-related factor-2 (Nrf2). Finally, inhibition of the Ca(2+)-CaMKII-ERK1/2-linked cascade attenuated significantly suppression by BDMC of LPS-induced iNOS expression and subsequent NO production. Collectively, our findings identify a Ca(2+)/calmodulin-CaMKII-ERK1/2-Nrf2 cascade as a novel anti-inflammatory pathway mediating BDMC signaling to HO-1 expression in macrophages.

Topics: Animals; Butadienes; Calcium; Calcium-Calmodulin-Dependent Protein Kinase Type 2; Cell Line; Curcumin; Diarylheptanoids; Gene Expression Regulation, Enzymologic; Heme Oxygenase-1; Inflammation; Lipopolysaccharides; Macrophages; Mice; Mitogen-Activated Protein Kinase 1; Mitogen-Activated Protein Kinase 3; NF-E2-Related Factor 2; NF-kappa B; Nitriles; Signal Transduction; Up-Regulation

Chronic inflammation and oxidative stress increase with advancing age and appear to be involved in the pathogenesis of coronary heart disease, the leading cause of death worldwide. There is a need for animal models that reflect the increases in pro-inflammatory cytokines and oxidative damage observed during aging in humans. We therefore aimed to investigate the suitability of the fast-aging senescence-accelerated mouse-prone 8 (SAMP8) strain and its normally aging control senescence-accelerated mouse-resistant 1 (SAMR1) to study the age-dependent changes in cytokines, oxidative damage and antioxidants in the heart. To this end, 2-months-old male SAMR1 and SAMP8 mice were fed a Western type diet (control groups) for 5 months. Two groups of SAMP8 mice were simultaneously fed identical diets fortified with 0.5 g curcumin or 1.0 g Ginkgo biloba extract EGb 761(®) per kg diet. Heart tissue homogenates were analysed for protein carbonyls, glutathione, glutathione disulfide, methionine, cysteine and uric acid as well as the cytokines tumor-necrosis factor-α, interleukin-1β, interleukin-6, and monocyte chemoattractant protein 1. Neither the strain (SAMR1 or SAMP8) nor antioxidant intake (curcumin or EGb 761(®)) affected the concentrations of the measured parameters. In conclusion, our data do not support the suitability of the SAMP8 and SAMR1 strains as a model to study age-related changes in pro-inflammatory cytokines and oxidative stress parameters in the heart.

Topics: Age Factors; Aging; Animals; Antioxidants; Atherosclerosis; Coronary Disease; Curcumin; Cytokines; Female; Ginkgo biloba; Heart; Humans; Inflammation; Interleukin-1beta; Interleukin-6; Male; Mice; Mice, Inbred C57BL; Mice, Inbred Strains; Models, Animal; Oxidative Stress; Plant Extracts; Protein Carbonylation

The health beneficial effects of Resveratrol, Curcumin and Simvastatin have been demonstrated in various experimental models of inflammation. We investigated the potential anti-inflammatory and immunomodulatory mechanisms of the above mentioned compounds in a murine model of hyper-acute Th1-type ileitis following peroral infection with Toxoplasma gondii.. Here we show that after peroral administration of Resveratrol, Curcumin or Simvastatin, mice were protected from ileitis development and survived the acute phase of inflammation whereas all Placebo treated controls died. In particular, Resveratrol treatment resulted in longer-term survival. Resveratrol, Curcumin or Simvastatin treated animals displayed significantly increased numbers of regulatory T cells and augmented intestinal epithelial cell proliferation/regeneration in the ileum mucosa compared to placebo control animals. In contrast, mucosal T lymphocyte and neutrophilic granulocyte numbers in treated mice were reduced. In addition, levels of the anti-inflammatory cytokine IL-10 in ileum, mesenteric lymph nodes and spleen were increased whereas pro-inflammatory cytokine expression (IL-23p19, IFN-γ, TNF-α, IL-6, MCP-1) was found to be significantly lower in the ileum of treated animals as compared to Placebo controls. Furthermore, treated animals displayed not only fewer pro-inflammatory enterobacteria and enterococci but also higher anti-inflammatory lactobacilli and bifidobacteria loads. Most importantly, treatment with all three compounds preserved intestinal barrier functions as indicated by reduced bacterial translocation rates into spleen, liver, kidney and blood.. Oral treatment with Resveratrol, Curcumin or Simvastatin ameliorates acute small intestinal inflammation by down-regulating Th1-type immune responses and prevents bacterial translocation by maintaining gut barrier function. These findings provide novel and potential prophylaxis and treatment options of patients with inflammatory bowel diseases.

Topics: Administration, Oral; Animals; Anti-Inflammatory Agents; Anti-Inflammatory Agents, Non-Steroidal; Curcumin; Disease Models, Animal; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Ileitis; Inflammation; Intestine, Small; Mice; Mice, Inbred C57BL; Resveratrol; Simvastatin; Stilbenes; Th1 Cells; Toxoplasma

The effects of Curcuma mangga ethanolic extract (CME) and its fractions, e.g., aqueous, chloroform, ethyl acetate, and hexane fractions, from C. mangga rhizome were investigated on nociceptive responses using writhing, hot plate, and formalin tests in mice and inflammatory models using carrageenan-induced rat paw edema and croton oil-induced mouse ear edema. The results showed that CME and all fractions (200 mg/kg, p.o.) significantly reduced the number of writhings. Oral administration (p.o.) of CME, chloroform, and hexane fractions (200 mg/kg) significantly prolonged the latency time, whereas aqueous and ethyl acetate fractions were inactive. The activities of CME, chloroform, and hexane fractions were abolished by naloxone (2 mg/kg, intraperitoneal (i.p.)). CME and all fractions at the dose of 200 mg/kg significantly produced antinociception in both early and late phases of the formalin test. CME, chloroform, and hexane fractions were more prominent in licking inhibition than those of the aqueous and ethyl acetate fractions. CME and all fractions (150 mg/kg, p.o.) showed significant reduction of rat paw edema. The order of activity on inhibition of paw edema at 4 h was chloroform fraction > hexane fraction > ethyl acetate fraction > CME > aqueous fraction. When topically applied at 0.5 mg/ear, CME and all fractions suppressed ear edema induced by croton oil. CME and chloroform fraction showed a greater inhibition by 53.97 and 50.29%, respectively. These results suggested that CME and its fractions, especially chloroform and hexane fractions from C. mangga rhizome, possessed centrally acting analgesic as well as anti-inflammatory activities.

Topics: Analgesics; Animals; Anti-Inflammatory Agents; Curcuma; Disease Models, Animal; Dose-Response Relationship, Drug; Female; Inflammation; Male; Mice; Pain; Plant Extracts; Rats; Rhizome; Solvents

Cerebral vasospasm is a major cause of death and disability after subarachnoid hemorrhage (SAH); however, clinical therapies to limit the development of cerebral vasospasm are lacking. Although the causative factors underlying the development of cerebral vasospasm are poorly understood, oxidative stress contributes to disease progression. In the present study, curcumin (150 or 300 mg/kg) protected against the development of cerebral vasospasm and limited secondary cerebral infarction after SAH in mice. The protective effect of curcumin was associated with a significant attenuation of inflammatory gene expression and lipid peroxidation within the cerebral cortex and the middle cerebral artery. Despite the ability of curcumin to limit the development of cerebral vasospasm and secondary infarction, behavioral outcome was not improved, indicating a dissociation between cerebral vasospasm and neurologic outcome. Together, these data indicate a novel role for curcumin as a possible adjunct therapy after SAH, both to prevent the development of cerebral vasospasm and to reduce oxidative brain injury after secondary infarction.

Topics: Animals; Curcumin; Disease Models, Animal; Endothelium, Vascular; Inflammation; Lipid Peroxidation; Male; Mice; Mice, Inbred Strains; NF-kappa B; Subarachnoid Hemorrhage; Superoxides; Thiobarbituric Acid Reactive Substances; Vasospasm, Intracranial

The aim of the present investigation was to develop and study topical gel delivery of curcumin for its anti-inflammatory effects. Carbopol 934P (CRB) and hydroxypropylcellulose (HPC) were used for the preparation of gels. The penetration enhancing effect of menthol (0-12.5% w/w) on the percutaneous flux of curcumin through the excised rat epidermis from 2% w/w CRB and HPC gel system was investigated. All the prepared gel formulations were evaluated for various properties such as compatibility, drug content, viscosity, in vitro skin permeation, and anti-inflammatory effect. The drug and polymers compatibility was confirmed by Differential scanning calorimetry and infrared spectroscopy. The percutaneous flux and enhancement ratio of curcumin across rat epidermis was enhanced markedly by the addition of menthol to both types of gel formulations. Both types of developed topical gel formulations were free of skin irritation. In anti-inflammatory studies done by carrageenan induced rat paw oedema method in wistar albino rats, anti-inflammatory effect of CRB, HPC and standard gel formulations were significantly different from control group (P < 0.05) whereas this effect was not significantly different for CRB and HPC gels formulations to that of standard (diclofenac gel) formulation (P > 0.05). CRB gel showed better % inhibition of inflammation as compared to HPC gel.

Topics: Acrylates; Administration, Topical; Animals; Anti-Infective Agents, Local; Calorimetry, Differential Scanning; Carrageenan; Cellulose; Chemistry, Pharmaceutical; Curcumin; Drug Evaluation, Preclinical; Edema; Excipients; Forelimb; Gels; Histocompatibility; Inflammation; Menthol; Permeability; Rats; Rats, Wistar; Skin Absorption; Spectrophotometry, Infrared; Viscosity

Present study was performed to assess the effect of curcumin treatment on macrophage functions using RAW264.7 cells, a murine macrophage cell line. Phagocytic activity of RAW264.7 cells was enhanced by the treatment with curcumin for 48 hours while the nitric oxide synthesis from RAW264.7 cells following lipopolysaccharide exposure was blocked. The incubation of RAW264.7 cells with curcumin dose-dependently inhibited the stimulatory responses of macrophage triggered by lipopolysaccharide; the enhanced secretion of inflammatory cytokines such as TNF-alpha and IL-1beta and the up-regulated expression of surface antigens like CD14 and CD40. Curcumin alone, however, was able to increase the basal level of TNF-alpha secretion and elevated markedly the expression of CD14 and slightly CD40. The marked enhancement of both phagocytic activity and CD14 was detectable as early as 75min after curcumin treatment which is the minimum time period required for the phagocytosis and CD14 measurement, suggesting a signaling pathway distinct from that triggered by apoptotic cells. In conclusion, this study elucidates that curcumin treatment enhances the phagocytic activity with blocking nitric oxide synthesis, a scavenger function of macrophages in non-inflammatory condition. In addition, this enhancement of phagocytic activity is triggered directly by the signals from curcumin itself not by apoptotic cells.

Topics: Animals; CD40 Antigens; Cell Cycle; Curcumin; Inflammation; Interleukin-1beta; Lipopolysaccharide Receptors; Lipopolysaccharides; Macrophages; Mice; Phagocytosis; Tumor Necrosis Factor-alpha

Curcumin (diferuloylmethane) is an orange-yellow compound from turmeric (Curcuma longa), a spice found in curry powder. Traditionally known for its anti-inflammatory effects, curcumin has established itself in the last two decades to be a potent immunomodulatory agent that can regulate the activation of a variety of immunocytes and the expression of inflammatory factors. Considering that the beta-diketone moiety of curcumin may result in its instability and poor metabolic property, we previously designed a series of mono-carbonyl analogues of curcumin with enhanced stability by deleting this moiety. These compounds demonstrate improved pharmacokinetic profiles both in vitro and in vivo. In this study, we reported a total of 44 mono-carbonyl analogues, which have been evaluated for the inhibitory activities against LPS-induced TNF-alpha and IL-6 release in the macrophages. Based on the screening results of these analogues, five active compounds A01, A03, A13, B18 and C22 were investigated to inhibit TNF-alpha and IL-6 release in a dose-dependent manner, three of which further demonstrated inhibitory effects on LPS-induced TNF-alpha, IL-1beta, IL-6, MCP-1, COX-2, PGES, iNOS and p65 NF-kappaB mRNA production. The results indicated that these mono-carbonyl analogues may possess anti-inflammatory activities similar to curcumin despite the absence of the beta-diketone. These mono-carbonyl analogues may be a favourable alternative for the development of curcumin-based anti-inflammatory drugs both pharmacokinetically and pharmacologically. We further examined the biological properties of A13, the only hydrosoluble analogue when combined with hydrochloric acid. The results showed a dose-dependent inhibition of LPS-induced cytokine production. These data further indicated that compound A13 may be explored as a promising anti-inflammatory molecule.

Topics: Animals; Carbon; Curcuma; Curcumin; Inflammation; Interleukin-6; Ketones; Lipopolysaccharides; Macrophages; Mice; Models, Chemical; Plant Extracts; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Tumor Necrosis Factor-alpha

Topics: Animals; Curcumin; Drug Delivery Systems; Humans; Inflammation; Randomized Controlled Trials as Topic

To study the mechanism of curcumin-attenuated inflammation and liver pathology in early stage of alcoholic liver disease, female Sprague-Dawley rats were divided into four groups and treated with ethanol or curcumin via an intragastric tube for 4 weeks. A control group treated with distilled water, and an ethanol group was treated with ethanol (7.5 g/kg bw). Treatment groups were fed with ethanol supplemented with curcumin (400 or 1 200 mg/kg bw). The liver histopathology in ethanol group revealed mild-to-moderate steatosis and mild necroinflammation. Hepatic MDA, hepatocyte apoptosis, and NF-kappaB activation increased significantly in ethanol-treated group when compared with control. Curcumin treatments resulted in improving of liver pathology, decreasing the elevation of hepatic MDA, and inhibition of NF-kappaB activation. The 400 mg/kg bw of curcumin treatment revealed only a trend of decreased hepatocyte apoptosis. However, the results of SOD activity, PPARgamma protein expression showed no difference among the groups. In conclusion, curcumin improved liver histopathology in early stage of ethanol-induced liver injury by reduction of oxidative stress and inhibition of NF-kappaB activation.

Topics: Analysis of Variance; Animals; Apoptosis; Curcumin; Ethanol; Fatty Liver, Alcoholic; Female; Histocytochemistry; Inflammation; Liver Diseases, Alcoholic; Malondialdehyde; Necrosis; Oxidative Stress; PPAR gamma; Rats; Rats, Sprague-Dawley; Superoxide Dismutase; Transcription Factor RelA

Recent studies have demonstrated that K-ras mutations in lung epithelial cells elicit inflammation that promotes carcinogenesis in mice (intrinsic inflammation). The finding that patients with chronic obstructive pulmonary disease (COPD), an inflammatory disease of the lung, have an increased risk of lung cancer after controlling for smoking suggests a further link between lung cancer and extrinsic inflammation. Besides exposure to cigarette smoke, it is thought that airway inflammation in COPD is caused by bacterial colonization, particularly with non-typeable Hemophilus influenzae (NTHi). Previously, we have shown that NTHi-induced COPD-like airway inflammation promotes lung cancer in an airway conditional K-ras-induced mouse model. To further test the role of inflammation in cancer promotion, we administered the natural anti-inflammatory agent, curcumin, 1% in diet before and during weekly NTHi exposure. This significantly reduced the number of visible lung tumors in the absence of NTHi exposure by 85% and in the presence of NTHi exposures by 53%. Mechanistically, curcumin markedly suppressed NTHi-induced increased levels of the neutrophil chemoattractant keratinocyte-derived chemokine by 80% and neutrophils by 87% in bronchoalveolar lavage fluid. In vitro studies of murine K-ras-induced lung adenocarcinoma cell lines (LKR-10 and LKR-13) indicated direct anti-tumoral effects of curcumin by reducing cell viability, colony formation and inducing apoptosis. We conclude that curcumin suppresses the progression of K-ras-induced lung cancer in mice by inhibiting intrinsic and extrinsic inflammation and by direct anti-tumoral effects. These findings suggest that curcumin could be used to protract the premalignant phase and inhibit lung cancer progression in high-risk COPD patients.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Antineoplastic Agents; Apoptosis; Cell Line, Tumor; Cell Proliferation; Cell Survival; Chemokines; Curcumin; Female; Genes, ras; Haemophilus Infections; Haemophilus influenzae; Inflammation; Lung Neoplasms; Male; Mice; Neutrophils; Pulmonary Disease, Chronic Obstructive

Currently available treatments for osteoarthritis (OA) are restricted to nonsteroidal anti-inflammatory drugs, which exhibit numerous side effects and are only temporarily effective. Thus novel, safe and more efficacious anti-inflammatory agents are needed for OA. Naturally occurring polyphenolic compounds, such as curcumin and resveratrol, are potent agents for modulating inflammation. Both compounds mediate their effects by targeting the NF-kappaB signalling pathway.. We have recently demonstrated that in chondrocytes resveratrol modulates the NF-kappaB pathway by inhibiting the proteasome, while curcumin modulates the activation of NF-kappaB by inhibiting upstream kinases (Akt). However, the combinational effects of these compounds in chondrocytes has not been studied and/or compared with their individual effects. The aim of this study was to investigate the potential synergistic effects of curcumin and resveratrol on IL-1beta-stimulated human chondrocytes in vitro using immunoblotting and electron microscopy.. Treatment with curcumin and resveratrol suppressed NF-kappaB-regulated gene products involved in inflammation (cyclooxygenase-2, matrix metalloproteinase (MMP)-3, MMP-9, vascular endothelial growth factor), inhibited apoptosis (Bcl-2, Bcl-xL, and TNF-alpha receptor-associated factor 1) and prevented activation of caspase-3. IL-1beta-induced NF-kappaB activation was suppressed directly by cocktails of curcumin and resveratrol through inhibition of Ikappakappa and proteasome activation, inhibition of IkappaBalpha phosphorylation and degradation, and inhibition of nuclear translocation of NF-kappaB. The modulatory effects of curcumin and resveratrol on IL-1beta-induced expression of cartilage specific matrix and proinflammatory enzymes were mediated in part by the cartilage-specific transcription factor Sox-9.. We propose that combining these natural compounds may be a useful strategy in OA therapy as compared with separate treatment with each individual compound.

Topics: Anti-Inflammatory Agents; Apoptosis; Blotting, Western; Cell Proliferation; Cells, Cultured; Chondrocytes; Curcumin; Drug Synergism; Humans; Inflammation; Interleukin-1beta; Microscopy, Electron, Transmission; NF-kappa B; Resveratrol; Signal Transduction; Stilbenes

Evidence has accumulated to suggest that systemic administration of lipopolysaccharide (LPS), in addition to elevating tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), and interleukin-6 (IL-6) as well as fever, induces overproduction of glutamate, hydroxyl radicals and prostaglandin E(2) (PGE(2)) in the rabbit's hypothalamus. Current study was attempted to assess whether Curcumin exerts its antipyresis by reducing circulating pro-inflammatory cytokines and hypothalamic glutamate, hydroxyl radicals and PGE(2) in rabbits. The microdialysis probes were stereotaxically and chronically implanted into the preoptic anterior hypothalamus of rabbit brain for determination of glutamate, hydroxyl radicals, and PGE(2) in situ. It was found that systemic administration of LPS (2 microg/kg) induced increased levels of both core temperature and hypothalamic levels of both glutamate and hydroxyl radicals accompanied by increased plasma levels of TNF-alpha, IL-1beta, and IL-6. The rise in both the core temperature and hypothalamic glutamate and hydroxyl radicals could also be induced by direct injection of TNF-alpha, IL-1beta, or IL-6 into the lateral ventricle of rabbit brain. Pretreatment with Curcumin (5-40 mg/kg, i.p.) 1 h before an i.v. dose of LPS significantly reduced the LPS-induced overproduction of circulating TNF-alpha, IL-1beta, and IL-6, and brain glutamate, PGE(2), and hydroxyl radicals. Both the febrile response and overproduction of both glutamate and hydroxyl radicals in the hypothalamus caused by central administration of TNF-alpha, IL-1beta, or IL-6 could be suppressed by Curcumin. These results indicate that systemic injection of Curcumin may exert its antipyresis by inhibiting the glutamate-hydroxyl radicals-PGE(2) pathways in the hypothalamus and circulating TNF-alpha, IL-1beta, and IL-6 accumulation during LPS fever.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Curcumin; Data Interpretation, Statistical; Dinoprostone; Fever; Glutamic Acid; Hydroxyl Radical; Hypothalamus; Inflammation; Injections, Intraventricular; Interleukin-1beta; Interleukin-6; Lipopolysaccharides; Male; Rabbits; Tumor Necrosis Factor-alpha

Porphyromonas gingivalis, a major periodontopathic bacterium, is necessary for periodontitis to take place. The lipopolysaccharide (LPS) of P. gingivalis stimulates cytokine secretion in immune cells, and thereby initiates the inflammation related to periodontitis. Macrophages are the important ones of the immune cells that are prominent at inflammatory periodontal sites. Curcumin, a major curcumanoid found in the spice turmeric, exhibits anti-inflammatory properties. The aim of this study was to investigate the anti-inflammatory effect and the mechanism of action of curcumin in macrophages stimulated by P. gingivalis LPS.. RAW264.7 cells pre-treated with various concentrations of curcumin were stimulated by P. gingivalis LPS. TNF-alpha and IL-1beta expressions were separately detected by RT-PCR and ELISA. Next, activation of NF-kappaB-dependent transcription was examined by luciferase assay.. Curcumin dose-dependently inhibited TNF-alpha and IL-1beta gene expression and protein synthesis in RAW264.7 cells stimulated with P. gingivalis LPS. P. gingivalis LPS activated NF-kappaB-dependent transcription in RAW264.7 cells, which were down-regulated by pre-treatment with curcumin as well.. Our data suggest that curcumin can inhibit P. gingivalis LPS-induced cytokine expression, and that this could be due to the inhibition of the NF-kappaB pathway.

Topics: Animals; Anti-Inflammatory Agents; Cell Line; Curcumin; Dose-Response Relationship, Drug; Enzyme-Linked Immunosorbent Assay; Gene Expression Regulation; Inflammation; Interleukin-1beta; Lipopolysaccharides; Luciferases; Macrophages; Mice; NF-kappa B; Periodontitis; Porphyromonas gingivalis; Reverse Transcriptase Polymerase Chain Reaction; Transcription, Genetic; Tumor Necrosis Factor-alpha

Chronic inhalation of high concentrations of respirable quartz particles has been implicated in various lung diseases including lung fibrosis and cancer. Generation of reactive oxygen species (ROS) and oxidative stress is considered a major mechanism of quartz toxicity. Curcumin, a yellow pigment from Curcuma longa, has been considered as nutraceutical because of its strong anti-inflammatory, antitumour and antioxidant properties. The aim of our present study was to investigate whether curcumin can protect lung epithelial cells from the cytotoxic, genotoxic and inflammatory effects associated with quartz (DQ12) exposure. Electron paramagnetic resonance (EPR) measurements using the spin-trap DMPO demonstrated that curcumin reduces hydrogen peroxide-dependent hydroxyl-radical formation by quartz. Curcumin was also found to reduce quartz-induced cytotoxicity and cyclooxygenase 2 (COX-2) mRNA expression in RLE-6TN rat lung epithelial cells (RLE). Curcumin also inhibited the release of macrophage inflammatory protein-2 (MIP-2) from RLE cells as observed upon treatment with interleukin-1 beta (IL-1beta) and tumour necrosis factor-alpha (TNFalpha). However, curcumin failed to protect the RLE cells from oxidative DNA damage induced by quartz, as shown by formamidopyrimidine glycosylase (FPG)-modified comet assay and by immunocytochemistry for 8-hydroxydeoxyguanosine. In contrast, curcumin was found to be a strong inducer of oxidative DNA damage itself at non-cytotoxic and anti-inflammatory concentrations. In line with this, curcumin also enhanced the mRNA expression of the oxidative stress response gene heme oxygenase-1 (ho-1). Curcumin also caused oxidative DNA damage in NR8383 rat alveolar macrophages and A549 human lung epithelial cells. Taken together, these observations indicate that one should be cautious in considering the potential use of curcumin in the prevention or treatment of lung diseases associated with quartz exposure.

Topics: Animals; Base Sequence; Cell Line; Cell Survival; Curcumin; DNA Damage; DNA Primers; Epithelial Cells; Humans; Inflammation; Lung; Oxidative Stress; Quartz; Rats; Reverse Transcriptase Polymerase Chain Reaction

We previously demonstrated that curcumin, a polyphenolic antioxidant purified from turmeric, up-regulated peroxisome proliferator-activated receptor (PPAR)-gamma gene expression and stimulated its signaling, leading to the inhibition of activation of hepatic stellate cells (HSC) in vitro. The current study evaluates the in vivo role of curcumin in protecting the liver against injury and fibrogenesis caused by carbon tetrachloride (CCl(4)) in rats and further explores the underlying mechanisms. We hypothesize that curcumin might protect the liver from CCl(4)-caused injury and fibrogenesis by attenuating oxidative stress, suppressing inflammation, and inhibiting activation of HSC. This report demonstrates that curcumin significantly protects the liver from injury by reducing the activities of serum aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase, and by improving the histological architecture of the liver. In addition, curcumin attenuates oxidative stress by increasing the content of hepatic glutathione, leading to the reduction in the level of lipid hydroperoxide. Curcumin dramatically suppresses inflammation by reducing levels of inflammatory cytokines, including interferon-gamma, tumor necrosis factor-alpha, and interleukin-6. Furthermore, curcumin inhibits HSC activation by elevating the level of PPARgamma and reducing the abundance of platelet-derived growth factor, transforming growth factor-beta, their receptors, and type I collagen. This study demonstrates that curcumin protects the rat liver from CCl(4)-caused injury and fibrogenesis by suppressing hepatic inflammation, attenuating hepatic oxidative stress and inhibiting HSC activation. These results confirm and extend our prior in vitro observations and provide novel insights into the mechanisms of curcumin in the protection of the liver. Our results suggest that curcumin might be a therapeutic antifibrotic agent for the treatment of hepatic fibrosis.

Topics: Animals; Antioxidants; Carbon Tetrachloride Poisoning; Curcumin; Inflammation; Liver; Liver Cirrhosis; Male; Oxidative Stress; Rats; Rats, Sprague-Dawley

Obesity is a major risk factor for the development of type 2 diabetes, and both conditions are now recognized to possess significant inflammatory components underlying their pathophysiologies. We tested the hypothesis that the plant polyphenolic compound curcumin, which is known to exert potent antiinflammatory and antioxidant effects, would ameliorate diabetes and inflammation in murine models of insulin-resistant obesity. We found that dietary curcumin admixture ameliorated diabetes in high-fat diet-induced obese and leptin-deficient ob/ob male C57BL/6J mice as determined by glucose and insulin tolerance testing and hemoglobin A1c percentages. Curcumin treatment also significantly reduced macrophage infiltration of white adipose tissue, increased adipose tissue adiponectin production, and decreased hepatic nuclear factor-kappaB activity, hepatomegaly, and markers of hepatic inflammation. We therefore conclude that orally ingested curcumin reverses many of the inflammatory and metabolic derangements associated with obesity and improves glycemic control in mouse models of type 2 diabetes. This or related compounds warrant further investigation as novel adjunctive therapies for type 2 diabetes in man.

Topics: Adiponectin; Adipose Tissue, White; Animals; Anti-Inflammatory Agents, Non-Steroidal; Antioxidants; Blood Glucose; Curcumin; Diabetes Mellitus, Type 2; Dietary Supplements; Disease Models, Animal; Gene Expression; Immunohistochemistry; Inflammation; Interleukin-6; Liver; Male; Mice; Mice, Inbred C57BL; Mice, Obese; NF-kappa B; Obesity; Reverse Transcriptase Polymerase Chain Reaction; Tumor Necrosis Factor-alpha

Curcumin can reduce inflammation and neurodegeneration, but its chemical instability and metabolism raise concerns, including whether the more stable metabolite tetrahydrocurcumin (TC) may mediate efficacy. We examined the antioxidant, anti-inflammatory, or anti-amyloidogenic effects of dietary curcumin and TC, either administered chronically to aged Tg2576 APPsw mice or acutely to lipopolysaccharide (LPS)-injected wild-type mice. Despite dramatically higher drug plasma levels after TC compared with curcumin gavage, resulting brain levels of parent compounds were similar, correlating with reduction in LPS-stimulated inducible nitric-oxide synthase, nitrotyrosine, F2 isoprostanes, and carbonyls. In both the acute (LPS) and chronic inflammation (Tg2576), TC and curcumin similarly reduced interleukin-1beta. Despite these similarities, only curcumin was effective in reducing amyloid plaque burden, insoluble beta-amyloid peptide (Abeta), and carbonyls. TC had no impact on plaques or insoluble Abeta, but both reduced Tris-buffered saline-soluble Abeta and phospho-c-Jun NH(2)-terminal kinase (JNK). Curcumin but not TC prevented Abeta aggregation. The TC metabolite was detected in brain and plasma from mice chronically fed the parent compound. These data indicate that the dienone bridge present in curcumin, but not in TC, is necessary to reduce plaque deposition and protein oxidation in an Alzheimer's model. Nevertheless, TC did reduce neuroinflammation and soluble Abeta, effects that may be attributable to limiting JNK-mediated transcription. Because of its favorable safety profile and the involvement of misfolded proteins, oxidative damage, and inflammation in multiple chronic degenerative diseases, these data relating curcumin dosing to the blood and tissue levels required for efficacy should help translation efforts from multiple successful preclinical models.

Topics: Alzheimer Disease; Animals; Biological Availability; Curcumin; Disease Models, Animal; Female; Inflammation; Male; Mice; Mice, Inbred C57BL; Structure-Activity Relationship

Goldenseal (Hydrastis canadenisis) is a native American medicinal plant used as an immune stimulant. Astragalus (Astragalus membranaceus) is a widely used herbal product in China, other Asian countries, and the United States as an immune stimulant to be taken on first clinical signs of infection. In this study, the innate effects of goldenseal and Astragalus on pro-inflammatory cytokines produced by cultured macrophages were examined using two different commercial preparations of goldenseal and Astragalus. Both goldenseal and Astragalus were found to exhibit little to no direct effect on stimulation of mouse macrophages (J774A.1 cells), with only Astragalus able to affect production of tumor necrosis factor (TNF)-alpha when used in high concentrations. However, both goldenseal and Astragalus were able to modify responses from lipopolysaccharide-stimulated macrophages, with identified immunomodulatory effects to reduce production of TNF-alpha, interleukin (IL)-6, IL-10, and IL-12 in a dose-dependent manner. The results obtained indicate that both goldenseal and Astragalus exhibit abilities to modulate macrophage responses during stimulation. Therefore, it is hypothesized that their historical use as therapeutic agents may be due to reduction in the pro-inflammatory response that indirectly leads to limiting of clinical symptoms during infection. Both products differ in their immune stimulatory patterns, offering insight into differential use and therapeutic potential of these products to regulate macrophage immune responses and activation events.

Topics: Animals; Astragalus Plant; Cell Line; Cells, Cultured; Cytokines; Hydrastis; Inflammation; Lipopolysaccharides; Macrophages; Mice; Phytotherapy; Plant Extracts

The experimental finding of Asian traditional medicine revealed the pharmacological effect of the local application of ghee which was taken from cow butterfat and the rhizomes of Curcuma longa. These materials significantly improved the healing process of the wound. In addition, ancient physicians of Middle East discovered that the powdered rhizomes of Curcuma longa (common turmeric) also had impressive medicinal qualities. Over the centuries, this spice has been used as a pain relieving, anti-inflammatory agent to relieve pain and inflammation in the skin and muscles.. We decided to mix ghee which was taken from sheep butterfat with the powdered rhizomes of Curcuma longa to formulate a novel cost-benefit material and then, evaluate its potential therapeutic effect on acceleration of surgical wound healing; moreover, this present study was performed to compare the effects of Curcuma longa-ghee formulation and hyaluronic acid on gingival wound healing following surgery.. Five healthy 3-year-old male beagle dogs were used in this study. They had intact teeth and the clinical and radiographic examination revealed no periodontal disease. Ghee was obtained from the refined sheep butterfat heated to 70 degrees C mixed with the powdered rhizomes of Curcuma longa and was applied with two different ratios including materials A and B. Randomly, these three materials including hyaluronic acid, materials A and B were applied topically in test regions and then covered with periodontal pack. Histological changes were monitored in days 4 and 7 after operation to evaluate the inflammatory and repair stage of healing process.. We observed significant difference in the inflammatory and repair parameters of the healing process between cases treated with this new formulation and cases of hyaluronic acid application.. The results suggested a positive potential therapeutic effect on surgical wound healing particularly improvement of periodontal treatment consequences after surgery.

Topics: Adjuvants, Immunologic; Animals; Cost-Benefit Analysis; Curcuma; Dietary Fats; Disease Models, Animal; Dogs; Gingiva; Gingivectomy; Hyaluronic Acid; Inflammation; Male; Medicine, Traditional; Phytotherapy; Random Allocation; Rhizome; Sheep; Wound Healing; Wounds and Injuries

To investigate the anti-inflammatory effect of topical application of Curcuma longa (C. longa) and Berberis aristata (B. aristata) aqueous extracts on experimental uveitis in the rabbit.. Anterior uveitis was induced in rabbits by intravitreal injection of lipopolysaccharide from Escherichia coli after pretreatment with C. longa and B. aristata aqueous extracts. Subsequently, the anti-inflammatory activity of C. longa and B. aristata was evaluated by grading the clinical signs and histopathologic changes and estimating the inflammatory cell count, protein, and TNF-alpha levels in the aqueous humor.. The anterior segment inflammation in the control group was significantly higher than in both the extract-treated groups, as observed by clinical and histopathologic grading. The inflammatory cell count in the control group was 30.75 +/- 7.33 x 10(5) cells/mL, whereas it was 2.39 +/- 0.59 x 10(5) (P < 0.001 vs. control) and 11.56 +/- 2.44 x 10(5) (P = 0.001 vs. control) cells/mL in the C. longa- and B. aristata-treated groups, respectively. The protein content of the aqueous humor was 18.14 +/- 4.98, 3.16 +/- 0.55 (P < 0.001 vs. control), and 8.24 +/- 1.42 (P < 0.01 vs. control) mg/mL in the control, C. longa-, and B. aristata-treated groups, respectively. The aqueous TNF-alpha level in the control group was 976.29 +/- 66.38 pg/mL and was 311.96 +/- 28.50 (P < 0.0001 vs. control) and 654.09 +/- 47.66 (P < 0.001vs. control) pg/mL in the C. longa- and B. aristata-treated groups, respectively.. Topical instillation of aqueous extracts of C. longa and B. aristata showed potent anti-inflammatory activity against endotoxin-induced uveitis in rabbits.

Topics: Animals; Anti-Inflammatory Agents; Berberis; Curcuma; Disease Models, Animal; Inflammation; Lipopolysaccharides; Plant Extracts; Rabbits; Uveitis

Curcumin is the main constituent of the spice turmeric, used in diet and in traditional medicine, particularly across the Indian subcontinent. Anti-inflammatory activity and inhibition of LPS signaling are some of its many activities. We show that curcumin binds at submicromolar affinity to the myeloid differentiation protein 2 (MD-2), which is the LPS-binding component of the endotoxin surface receptor complex MD-2/TLR4. Fluorescence emission of curcumin increases with an absorbance maximum shift toward the blue upon the addition of MD-2, indicating the transfer of curcumin into the hydrophobic environment. Curcumin does not form a covalent bond to the free thiol group of MD-2, and C133F mutant retains the binding and inhibition by curcumin. The binding site for curcumin overlaps with the binding site for LPS. This results in the inhibition of MyD88-dependent and -independent signaling pathways of LPS signaling through TLR4, indicating that MD-2 is one of the important targets of curcumin in its suppression of the innate immune response to bacterial infection. This finding, in addition to the correlation between the dietary use of curcumin and low incidence of gastric cancer in India, may have important implications for treatment and epidemiology of chronic inflammatory diseases caused by bacterial infection.

Topics: Amino Acid Substitution; Antineoplastic Agents; Bacterial Infections; Binding Sites; Cell Line; Chronic Disease; Curcumin; Humans; Immunity, Innate; India; Inflammation; Lipopolysaccharides; Lymphocyte Antigen 96; Mutation, Missense; Myeloid Differentiation Factor 88; Stomach Neoplasms; Toll-Like Receptor 4

Curcumin, a yellow pigment of turmeric in curry, is reported to interfere with nuclear factor (NF)-kappaB. This study was designed to investigate the underlying pathway of antiinflammation of curcumin on endothelial cells. Human umbilical vein endothelial cells (HUVECs) were stimulated with 10 ng/mL tumor necrosis factor (TNF)-alpha. Curcumin blocked the activation of NF-kappaB by TNF-alpha. Curcumin also reduced the intracellular reactive oxygen species (ROS), monocyte adhesion, phosphorylation of c-Jun N-terminal kinase (JNK), p38, and signal transducer and activator of transcription (STAT)-3 in TNF-alpha-stimulated HUVECs. The expression of intracellular cell adhesion molecule (ICAM)-1, monocyte chemoattractant protein (MCP)-1, and interleukin (IL)-8 were attenuated by curcumin at both mRNA and protein level. Curcumin, however, did not affect the expression of TNF receptor I and II in TNF-alpha-stimulated HUVECs. We suggest that curcumin could contribute to protection against the adverse vascular effect of the proinflammatory response through the modulation of p38 and STAT-3 in addition to NF-kappaB and JNK in endothelial cells.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Cells, Cultured; Curcumin; Endothelium, Vascular; Gene Expression; Humans; Inflammation; Intercellular Adhesion Molecule-1; JNK Mitogen-Activated Protein Kinases; Monocytes; NF-kappa B; p38 Mitogen-Activated Protein Kinases; Phosphorylation; Reactive Oxygen Species; Receptors, Tumor Necrosis Factor; RNA, Messenger; STAT3 Transcription Factor; Tumor Necrosis Factor-alpha; Umbilical Veins

Chronic alcohol drinking has been associated with the development of a number of abnormalities, including neuron-behavioral disorders, liver, pancreas, and heart-related diseases and inflammation and immune disorders. Because diverse mechanisms are involved in the development of these disorders, the commonly used receptor- or enzyme-specific drugs do not provide comprehensive protection against the adverse effects of alcoholism. This study describes possible therapeutic potency of puerarin (PU) from kudzu root, polyenylphosphatidylcholine from soy (SPCh), and curcumin (CU) from turmeric against alcohol's addiction-related and inflammatory-related abnormalities in alcohol-preferring P rats receiving free choice water and 15% ethanol in water. P-rats were fed once daily either the vehicle (for control) or different doses of PU, SPCh, CU, PU + SPCh, or PU + CU. The rats were divided in two groups: one received water alone, and the other free choice water and ethanol. Four rats from each group were fitted with electroencephalogram (EEG) electrodes for EEG recording. After 70 days of alcohol drinking, alcohol was withdrawn for 2 weeks, and the withdrawal symptoms were assessed. This study showed that alcohol drinking for 70 days (1) caused liver inflammation characterized by elevated tumor necrosis factor-alpha, interleukin-1beta, and matrix metalloproteinase-9 expression and (2) dysregulated lipopolysaccharide (LPS)-induced pleurisy. Alcohol withdrawal after 70 days of drinking generated severe withdrawal symptoms including seizure-type EEG activity. PU suppressed the addiction-mediated abnormalities but did not affect the inflammation-related abnormalities, while SPCh or CU suppressed only the inflammation-related abnormalities in alcohol-drinking rats subjected to LPS-induced pleurisy. A combination of PU with SPCh or CU suppressed both the addiction-related and inflammation-related abnormalities of alcohol drinking. Therefore, a mixture consisting of PU and either SPCh or CU may provide alternative therapy for alcohol-related disorders.

Topics: Acetaldehyde; Alcohol-Related Disorders; Alcoholism; Animals; Apoptosis; Curcumin; Electroencephalography; Ethanol; Female; Hepatitis, Alcoholic; Inflammation; Interleukin-1beta; Isoflavones; Liver; Matrix Metalloproteinase 9; Monocytes; Phosphatidylcholines; Phytotherapy; Pleural Effusion; Rats; RNA, Messenger; Tumor Necrosis Factor-alpha

Nephrotoxicity is a major complication and a dose limiting factor for cisplatin therapy. Recent evidence suggests that inflammation and oxidative stress may contribute to the pathogenesis of cisplatin-induced acute renal failure. Curcumin is claimed to be a potent anti-inflammatory and antioxidant agent. The present study was performed to explore the effect of curcumin against cisplatin-induced experimental nephrotoxicity. Curcumin in the dosages of 15, 30, and 60 mg kg(-1) was administered 2 days before and 3 days after cisplatin administration. Renal injury was assessed by measuring serum creatinine, blood urea nitrogen, creatinine, urea clearance, and serum nitrite levels. Renal oxidative stress was assessed by determining renal malondialdehyde levels, reduced glutathione levels and enzymatic activities of superoxide dismutase and catalase. Systemic inflammation was assessed by tumor necrosis factor-alpha (TNF-alpha) levels. A single dose of cisplatin resulted in marked inflammation (486% rise in TNF-alpha level) and oxidative stress and significantly deranged renal functions as well as renal morphology. The serum TNF-alpha level was markedly reduced in curcumin-treated rats. Curcumin treatment significantly and dose-dependently restored renal function, reduced lipid peroxidation, and enhanced the levels of reduced glutathione and activities of superoxide dismutase and catalase. The present study demonstrates that curcumin has a protective effect on cisplatin-induced experimental nephrotoxicity, and this effect is attributed to its direct anti-inflammatory and strong antioxidant profile. Hence, curcumin has a strong potential to be used as a therapeutic adjuvant in cisplatin nephrotoxicity.

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Cisplatin; Curcumin; Inflammation; Kidney Diseases; Lipid Peroxidation; Male; Oxidative Stress; Rats; Rats, Wistar; Tumor Necrosis Factor-alpha

Curcumin and quercetin are antioxidant molecules with anti-proliferative, anti-inflammatory and immunosuppressive activities. The objective of this study was to investigate the inhibitory activity of these agents using four assays of inflammatory aspects of arthritis.. Crystal-induced neutrophil activation was measured by luminol-dependent chemiluminescence. Synoviocyte proliferation was measured by an MTS assay using HIG-82 rabbit synoviocytes in cell culture. Chondrocyte (cultured primary cells) expression of the matrix metalloproteinases collagenase and stromelysin was measured by Northern Blot analysis. Angiogenesis was measured using the chorioallantoic membrane of the chick embryo.. Both agents inhibited neutrophil activation, synoviocyte proliferation and angiogenesis. Curcumin strongly inhibited collagenase and stromelysin expression at micromolar concentrations whereas quercetin had no effect in this assay.. These studies suggest that curcumin and to a lesser extent quercetin may offer therapeutic potential for the treatment of crystal-induced arthritis or rheumatoid arthritis.

Topics: Animals; Antioxidants; Apoptosis; Arthritis; Cattle; Cell Line; Cell Proliferation; Chondrocytes; Collagenases; Curcumin; Gene Expression Regulation; Inflammation; Interleukin-1; Luminescent Measurements; Matrix Metalloproteinase 3; Neutrophils; Proteoglycans; Quercetin; Rabbits

The beneficial influence of dietary curcumin, capsaicin and their combination on the susceptibility of low-density lipoprotein (LDL) to oxidation was examined in an animal study. Individually, both dietary curcumin and capsaicin significantly inhibited the in vivo iron-induced LDL oxidation, as well as copper-induced oxidation of LDL in vitro. The protective effect of the combination of curcumin and capsaicin on LDL oxidation was greater than that of individual compounds. This protective influence of spice principles was also indicated by the relative anodic electrophoretic mobility of oxidized LDL on agarose gel. In another study, rats injected with iron showed hepatic toxicity as measured by an increase in lipid peroxides and elevated serum enzymes, alanine aminotransferase, aspartate aminotransferase and lactate dehydrogenase. Dietary curcumin, capsaicin and their combination reduced the activities of these enzymes, and lowered the liver lipid peroxide level, indicating amelioration of the severity of iron-induced hepatotoxicity. In yet another study, a comparison of the extent of carrageenan-induced paw inflammation showed that both dietary curcumin and capsaicin moderately lowered inflammation, while the spice principles in combination were more effective. Dietary curcumin and capsaicin significantly decreased the activity of 5'-lipoxygenase activity in the polymorphonuclear lymphocytes in carrageenan-injected rats, the decrease being even higher in the case of combination of these two spice principles. Results suggest that dietary curcumin and capsaicin individually are protective to LDL oxidation both in vivo and in vitro, to iron-induced hepatotoxicity and to carrageenan-induced inflammation. This beneficial effect was higher when the two compounds were fed in combination.

Topics: Animals; Arachidonate 5-Lipoxygenase; Capsaicin; Carrageenan; Copper; Curcumin; Diet; Inflammation; Iron; Lipoproteins, LDL; Liver; Male; Neutrophils; Oxidation-Reduction; Rats; Rats, Wistar

We investigated poly(L-lactic acid) (PLLA) fibers and coils, simulating stents and the influence of impregnation with curcumin, a non-steroidal anti-inflammatory drug, intended to reduce the pro-inflammatory property of these implants. Fibers obtained by melt extrusion of 137 kDa PLLA resin containing 10% curcumin (C-PLLA) exhibited a stable curcumin release rate for periods up to 36 days. Curcumin increased the fiber tensile strength at break and decreased embrittlement vs. controls in 36 day 37 degrees C saline incubation. A mouse peritoneal phagocyte model was employed to test the anti-inflammatory properties of C-PLLA fibers in vitro. Myeloperoxidase and non-specific esterase activity assays were performed for adherent cells (polymorphonuclear leukocytes (PMN) and macrophages (MPhi), respectively). PMN and MPhi adhesion to C-PLLA fibers were significantly reduced compared to control PLLA fibers (2.6 +/- 0.91) x 10(5) vs. (5.6 +/- 0.67) x 10(5) PMN/cm2 and (3.9 +/- 0.23) x 10(3) vs. (9.1 +/- 0.7) x 10(3) MPhi/cm2 (P < 0.05), respectively. In addition, superoxide release in the phagocyte pool contacting C-PLLA fibers was 97% less than that for PLLA controls. A fresh human whole blood recirculation system was employed to analyze cell adhesion under flow conditions, employing scanning electron microscopy (SEM). Reduced adhesion of cells on C-PLLA fiber coils vs. controls was observed. These in vitro studies demonstrate that bulk curcumin impregnation can reduce the inflammatory response to bioresorbable PLLA fibers, whilst improving mechanical properties, thereby suggesting curcumin loading may benefit PLLA-based implants.

Topics: Animals; Anti-Inflammatory Agents; Anti-Inflammatory Agents, Non-Steroidal; Biocompatible Materials; Cell Adhesion; Curcumin; Flow Cytometry; Humans; Inflammation; Lactic Acid; Macrophages; Materials Testing; Mice; Microscopy, Electron, Scanning; Neutrophils; Peritoneum; Peroxidase; Phagocytes; Polyesters; Polymers; Superoxides; Surface Properties; Temperature; Tensile Strength; Time Factors

The use of turmeric, derived from the root of the plant Curcuma longa, for treatment of different inflammatory diseases has been described in Ayurveda and in traditional Chinese medicine for thousands of years. The active component of turmeric responsible for this activity, curcumin, was identified almost two centuries ago. Modern science has revealed that curcumin mediates its effects by modulation of several important molecular targets, including transcription factors (e.g., NF-kappaB, AP-1, Egr-1, beta-catenin, and PPAR-gamma), enzymes (e.g., COX2, 5-LOX, iNOS, and hemeoxygenase-1), cell cycle proteins (e.g., cyclin D1 and p21), cytokines (e.g., TNF, IL-1, IL-6, and chemokines), receptors (e.g., EGFR and HER2), and cell surface adhesion molecules. Because it can modulate the expression of these targets, curcumin is now being used to treat cancer, arthritis, diabetes, Crohn's disease, cardiovascular diseases, osteoporosis, Alzheimer's disease, psoriasis, and other pathologies. Interestingly, 6-gingerol, a natural analog of curcumin derived from the root of ginger (Zingiber officinalis), exhibits a biologic activity profile similar to that of curcumin. The efficacy, pharmacologic safety, and cost effectiveness of curcuminoids prompt us to "get back to our roots."

Topics: Alzheimer Disease; Arthritis, Rheumatoid; Atherosclerosis; Blood Glucose; Curcumin; Diabetes Mellitus, Type 2; Humans; India; Inflammation; Multiple Sclerosis; Myocardial Infarction; Plant Roots; Transcription, Genetic

Inflammatory cytokines interleukin 1 (IL-1), IL-2, IL-6, and tumor necrosis factor-alpha (TNF-alpha) have been recognized as important mediators of pathophysiological and immunological events associated with shock. These inflammatory events after hemorrhage and resuscitation are characterized by the activation of transcription regulators such as nuclear factor-kappaB (NF-kappaB) and activator protein-1 (AP-1). Curcumin, an anti-inflammatory remedy used in Indian medicine, is known to suppress NF-kappaB and AP-1 activation and also to reduce ischemia-reperfusion injuries in animal models. Therefore, the aim of this study was to determine whether administration of curcumin before hemorrhagic shock has any salutary effects on cytokines and the redox-sensitive transcription factors NF-kappaB and AP-1. mRNA levels of IL-1alpha, IL-1beta, IL-2, IL-6, IL-10, and TNF-alpha were determined by reverse transcriptase-polymerase chain reaction in rat livers collected at 2 and 24 h after hemorrhage/resuscitation. The effect of curcumin on the activation of NF-kappaB and AP-1 was determined by electrophoretic mobility shift assays. Significant increases in the levels of liver cytokines IL-1alpha, IL-1beta, IL-2, IL-6, and IL-10 were observed in the 2-h posthemorrhage/resuscitation group compared with sham animals. In contrast, oral administration of curcumin for 7 days followed by hemorrhage/resuscitation regimen resulted in significant restoration of these cytokines to depleted levels, and, in fact, IL-1beta levels were lower than sham levels. Also, the 24-h postresuscitation group showed similar patterns with some exceptions. NF-kappaB and AP-1 were differentially activated at 2 and 24 h posthemorrhage and were inhibited by curcumin pretreatment. Serum aspartate transaminase estimates indicate decreased liver injury in curcumin-pretreated hemorrhage animals. These results suggest that protection against hemorrhage/resuscitation injury by curcumin pretreatment may result from the inactivation of transcription factors involved and regulation of cytokines to beneficial levels.

Topics: Animals; Aspartate Aminotransferases; Blotting, Western; Cell Nucleus; Curcumin; Cytokines; Enzyme Inhibitors; Hemorrhage; Inflammation; Interleukin-1; Interleukin-10; Interleukin-2; Interleukin-6; Liver; Male; Proto-Oncogene Proteins c-fos; Proto-Oncogene Proteins c-jun; Rats; Rats, Sprague-Dawley; Resuscitation; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Time Factors; Transcription Factor AP-1; Transcription Factors; Tumor Necrosis Factor-alpha

We previously reported that a phenolic compound, petasiphenol, was a selective inhibitor of DNA polymerase lambda (pol lambda) in vitro. We found here that another phenolic compound, curcumin (diferuloylmethane), which is known as an anti-chronic inflammatory agent and is structurally quite similar to petasiphenol, was also a potent pol lambda inhibitor. The IC(50) values of petasiphenol and curcumin were 7.8 and 7.0 microM, respectively. Curcumin, as well as petasiphenol, did not influence the activities of replicative DNA polymerases, such as alpha, gamma, delta, and epsilon, but also showed no effect even on the pol beta activity belonging to the X family. Curcumin could prevent the growth of human NUGC-3 cancer cells with LD(50) values of 13 microM, and halted them at the G2/M phase in the cell cycle, whereas petasiphenol suppressed the cell growth at 66 microM and arrested the cells at the G1 phase. These data showed that curcumin and petasiphenol were slightly different functionally. We also previously reported that novel anti-inflammatory terpeno benzoic acids and triterpenoids were inhibitors of mammalian DNA polymerases. They could also efficiently inhibit the pol lambda activity, although they influenced the other polymerase species to the same extent, suggesting that there may be a physiological relationship between pol lambda inhibition and anti-12-O-tetradecanoylphorbol-13-acetate-induced inflammation. Expectedly, petasiphenol also showed an anti-12-O-tetradecanoylphorbol-13-acetate-induced inflammatory effect in mice. This finding may provide clues to investigating the molecular mechanism of inflammation.

Topics: Animals; Anti-Inflammatory Agents; Caffeic Acids; Cell Division; Curcumin; DNA Polymerase beta; Enzyme Inhibitors; Humans; Inflammation; Mice; Phenols; Tetradecanoylphorbol Acetate

Curcumin has been strongly implicated as an anti-inflammatory agent, but the precise mechanisms of its action are largely unknown. In this study, we show that the inhibitory action of curcumin on Janus kinase (JAK)-STAT signaling can contribute to its anti-inflammatory activity in the brain. In both rat primary microglia and murine BV2 microglial cells, curcumin effectively suppressed the ganglioside-, LPS-, or IFN-gamma-stimulated induction of cyclooxygenase-2 and inducible NO synthase, important enzymes that mediate inflammatory processes. These anti-inflammatory effects appear to be due, at least in part, to the suppression of the JAK-STAT inflammatory signaling cascade. Curcumin markedly inhibited the phosphorylation of STAT1 and 3 as well as JAK1 and 2 in microglia activated with gangliosides, LPS, or IFN-gamma. Curcumin consistently suppressed not only NF binding to IFN-gamma-activated sequence/IFN-stimulated regulatory element, but also the expression of inflammation-associated genes, including ICAM-1 and monocyte chemoattractant protein 1, whose promoters contain STAT-binding elements. We further show that activation of Src homology 2 domain-containing protein tyrosine phosphatases (SHP)-2, a negative regulator of JAK activity, is likely to be one of the mechanisms underlying the curcumin-mediated inhibition of JAK-STAT signaling. Treatment of microglial cells with curcumin led to an increase in phosphorylation and association with JAK1/2 of SHP-2, which inhibit the initiation of JAK-STAT inflammatory signaling in activated microglia. Taken together, these data suggest curcumin suppresses JAK-STAT signaling via activation of SHP-2, thus attenuating inflammatory response of brain microglial cells.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Brain; Cells, Cultured; Curcumin; Cyclooxygenase 2; DNA-Binding Proteins; Down-Regulation; Gene Expression Regulation; Inflammation; Interferon-gamma; Intracellular Signaling Peptides and Proteins; Isoenzymes; Janus Kinase 1; Janus Kinase 2; Microglia; Nitric Oxide Synthase; Nitric Oxide Synthase Type II; Phosphorylation; Prostaglandin-Endoperoxide Synthases; Protein Phosphatase 2; Protein Tyrosine Phosphatase, Non-Receptor Type 11; Protein Tyrosine Phosphatases; Protein-Tyrosine Kinases; Proto-Oncogene Proteins; Rats; Rats, Sprague-Dawley; Regulatory Sequences, Nucleic Acid; SH2 Domain-Containing Protein Tyrosine Phosphatases; Signal Transduction; src Homology Domains; STAT1 Transcription Factor; STAT3 Transcription Factor; Trans-Activators; Up-Regulation

Alpinia oxphylla Miquel, which belongs to the ginger family (Zingiberaceae), has been used in Oriental herbal medicine. Our recent studies have revealed that the methanolic extract of A. oxyphylla suppresses mouse skin tumor promotion and induces apoptosis in cultured human promyelocytic leukemia cells. In the present work, we have assessed effects of yakuchinone A and yakuchinone B, phenolic diarylheptanoids derived from A. oxyphylla, on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced inflammation and epidermal ornithine decarboxylase (ODC) activity as well as on skin tumor promotion in female ICR mice. Thus, topical application of 2 or 6 micromol of the diarylheptanoids prior to each topical dose of TPA significantly ameliorated 7,12-dimethylbenz[a]anthracene-initiated mouse skin tumor formation. In parallel with suppression of tumor promotion, topically applied yakuchinone A and B markedly inhibited TPA-induced epidermal ODC activity and ODC mRNA expression. In another experiment, yakuchinone A and B reduced production of tumor necrosis factor-alpha in TPA-stimulated mouse skin. Furthermore, both compounds inhibited the TPA-induced expression of cyclooxygenase-2 at both transcriptional and translational levels. These findings indicate that pungent diarylheptanoids from A. oxyphylla Miquel have an antitumor promotional activity that might be related to their anti-inflammatory properties.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Curcumin; Diarylheptanoids; Edema; Guaiacol; Inflammation; Mice; Phytotherapy; Skin; Skin Neoplasms; Zingiber officinale

Curcumin, a natural constituent of Curcuma longa (turmeric, CAS 458-37-7) was formulated as prolonged release biodegradable microspheres for treatment of inflammation. Natural biodegradable polymers, namely, bovine serum albumin and chitosan were used to encapsulate curcumin to form a depot forming drug delivery system. Microspheres were prepared by emulsion-solvent evaporation method coupled with chemical cross-linking of the natural polymers. Curcumin could be encapsulated into the biodegradable carriers upto an extent of 79.49 and 39.66% respectively with albumin and chitosan. Different drug:polymer ratios did not affect the mean particle size or particle size distribution significantly. However, the concentration of the crosslinking agent had remarkable influence on the drug release. In-vitro release studies indicated a biphasic drug release pattern, characterized by a typical burst-effect followed by a slow release which continued for several days. Evaluation of antinflammatory activity using Freund's adjuvant induced arthritic model in Wistar rats revealed significant difference between both the formulations, albumin microspheres and chitosan micropheres as well as against control. It was evident from the present study that the curcumin biodegradable microspheres could be successfully employed as prolonged release drug delivery system for better therapeutic management of inflammation as compared to oral or subcutaneous route.

Topics: Absorbable Implants; Animals; Chemistry, Pharmaceutical; Curcumin; Inflammation; Male; Microspheres; Rats; Rats, Wistar

Persistent expression of pro-inflammatory cytokines is believed to play a major role in the pathogenesis of chronic lung disease (CLD) in premature infants. Inhibition of pro-inflammatory cytokine production in the lungs of preterm newborns may result in the attenuation of CLD. Curcumin is a naturally occurring phenolic compound derived from the food spice tumeric with broad based in vitro anti-inflammatory properties. In this study lung inflammatory cells from preterm newborns at risk for the development of CLD were derived via modified broncho-alveolar lavage and stimulated ex vivo with lipopolysaccharide (LPS) (10 ng/ml). Curcumin was added to these cultures at 0, 0.5 and 20 uM concentrations. Pro-inflammatory cytokine, TNFalpha, IL-1beta and IL-8 protein was measured from the culture supernatants 12 hours post culture. For control, adult peripheral blood mononuclear cells (PBMC) were cultured under the same conditions. Both neonatal lung inflammatory cells and adult PBMC produced high levels of pro-inflammatory cytokines in response to LPS. Curcumin produced significant inhibition of IL-1beta and IL-8 but minimal inhibition of TNFalpha expression by preterm lung inflammatory cells at 20 uM concentrations. Adult PBMC expression of IL-8 was significantly inhibited by curcumin at 20 uM concentrations. Therefore, curcumin inhibits pro-inflammatory cytokine production (TNFalpha, IL-1beta and IL-8) by lung inflammatory cells ex vivo. Pathways involved with curcumin regulation of these cytokines are developmentally intact and functional in premature infants. Curcumin may be effective as a therapeutic agent in the attenuation of CLD.

Topics: Adult; Anti-Inflammatory Agents, Non-Steroidal; Bronchoalveolar Lavage Fluid; Coculture Techniques; Curcumin; Cytokines; Enzyme-Linked Immunosorbent Assay; Humans; Hyaline Membrane Disease; Infant, Newborn; Inflammation; Lipopolysaccharides

NF-kappa B plays a critical role in the transcriptional regulation of proinflammatory gene expression in various cells. Cytokine-mediated activation of NF-kappa B requires activation of various kinases, which ultimately leads to the phosphorylation and degradation of I kappa B, the NF-kappa B cytoplasmic inhibitor. The food derivative curcumin has been shown to inhibit NF-kappa B activity in some cell types. In this report we investigate the mechanism of action of curcumin on cytokine-induced proinflammatory gene expression using intestinal epithelial cells (IEC). Curcumin inhibited IL-1 beta-mediated ICAM-1 and IL-8 gene expression in IEC-6, HT-29, and Caco-2 cells. Cytokine-induced NF-kappa B DNA binding activity, RelA nuclear translocation, I kappa B alpha degradation, I kappa B serine 32 phosphorylation, and I kappa B kinase (IKK) activity were blocked by curcumin treatment. Wound-induced p38 phosphorylation was not inhibited by curcumin treatment. In addition, mitogen-activated protein kinase/ERK kinase kinase-1-induced IL-8 gene expression and 12-O-tetraphorbol 12-myristate 13-acetate-responsive element-driven luciferase expression were inhibited by curcumin. However, I kappa B alpha degradation induced by ectopically expressed NF-kappa B-inducing kinase or IKK was not inhibited by curcumin treatment. Therefore, curcumin blocks a signal upstream of NF-kappa B-inducing kinase and IKK. We conclude that curcumin potently inhibits cytokine-mediated NF-kappa B activation by blocking a signal leading to IKK activity.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Cell Line; Curcumin; Cytokines; DNA-Binding Proteins; Enzyme Activation; Enzyme Inhibitors; Gene Expression Regulation; HT29 Cells; Humans; I-kappa B Kinase; I-kappa B Proteins; Inflammation; Intercellular Adhesion Molecule-1; Interleukin-8; Intestinal Mucosa; MAP Kinase Kinase Kinase 1; NF-kappa B; Phosphorylation; Protein Serine-Threonine Kinases; Rats; Signal Transduction

A wide array of phytochemicals have been shown to possess potential cancer chemopreventive properties. Ginger contains pungent phenolic substances with pronounced antioxidative and antiinflammatory activities. In the present study, we have determined the antitumor promotional activity of [6]-gingerol, a major pungent principle of ginger, using a two-stage mouse skin carcinogenesis model. Topical application of [6]-gingerol onto shaven backs of female ICR mice prior to each topical dose of 12-O-tetradecanoylphorbol-13-acetate (TPA) significantly inhibited 7,12-dimethylbenz[a]anthracene-induced skin papillomagenesis. The compound also suppressed TPA-induced epidermal ornithine decarboxylase activity and inflammation.

Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Capillary Permeability; Catechols; Curcumin; Epidermis; Fatty Alcohols; Female; Inflammation; Mice; Mice, Inbred ICR; Ornithine Decarboxylase; Ornithine Decarboxylase Inhibitors; Plants, Medicinal; Skin Neoplasms; Tetradecanoylphorbol Acetate

Brown Norway rats were primed intraperitoneally with beta-lactoglobulin for 3 wk to induce reaginic antibody, during which time they were fed diets containing 10% each of coconut oil (CO), high oleic safflower oil, safflower oil (SO), or fish oil, then they were challenged for 3 h orally with the antigen. The dietary SO, compared to other dietary fats, resulted in lower circulatory release of rat chymaseII (RChyII), an indicator of degranulation of mucosal mast cells in the intestine, in response to the antigen. Addition of 0.5% curcumin to the CO or SO diet lowered the release. The SO diet, compared to CO diet, tended to increase the concentration of reaginic antibody, but the influence of curcumin addition was not prominent. These results indicate that dietary ingredients differently influence the synthesis of immunoglobulin E and degranulation of mast cells.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Cell Degranulation; Curcumin; Dietary Fats; Food Hypersensitivity; Immunoglobulin E; Inflammation; Intestines; Lactoglobulins; Linoleic Acids; Mast Cells; Rats; Rats, Inbred BN; Rats, Sprague-Dawley

In chronic inflammation, cytokines induce the production of nitric oxide (NO.) that is converted to DNA damaging and carcinogenic peroxynitrite and nitrite. The compounds epigallocatechin gallate (EGCG), carnosol, and curcumin are non-vitamin phytochemicals contained in commonly consumed dietary plants. They are known to be anti-inflammatory and cancer preventive. Therefore, we studied their effect on the generation of peroxynitrite radicals and nitrite. They inhibited lipopolysaccharide (LPS) and interferon-gamma (IFN gamma) induced nitrite production by mouse peritoneal cells by more than 50% at 2.5-10 microM. Cell viability assays verified that the inhibition was not due to general cellular toxicity.

Topics: Abietanes; Animals; Anti-Inflammatory Agents, Non-Steroidal; Antioxidants; Catechin; Cell Survival; Curcumin; Inflammation; Interferon-gamma; Lipopolysaccharides; Macrophage Activation; Macrophages; Mice; Mice, Inbred BALB C; Nitrites; Phenanthrenes; Recombinant Proteins; Spices; Tea; Tumor Necrosis Factor-alpha

The antioxidant spice principles curcumin and eugenol when given by gavage lowered the carrageenan-induced edema in the foot pads of rats. This lowering effect was dependent on the concentration, the time gap between the administration of spice principles and the induction of inflammation by carrageenan. Dietary lipids also influenced the extent of inflammation. Animals fed 10% cod liver oil [containing n-3 polyunsaturated fatty acids (PUFA)] for 10 weeks showed a significantly lower inflammation compared to that observed in animals fed diets supplemented with 10% groundnut oil (rich in n-6 PUFA) or 10% coconut oil (rich in medium-chain saturated fatty acids). Supplementation of diets with 1 weight% of curcumin did not affect the inflammatory responses of animals to carrageenan injection. However, supplementation of diets with 0.17 weight% eugenol further lowered inflammation by 16, 32 and 30% in animals fed coconut oil, groundnut oil and cod liver oil, respectively. Therefore, combinations of dietary lipids with spice principles like eugenol can help in lowering inflammation.

Topics: Administration, Oral; Animals; Antioxidants; Carrageenan; Curcumin; Dietary Fats; Dietary Fats, Unsaturated; Dose-Response Relationship, Drug; Edema; Eugenol; Fatty Acids, Omega-3; Fatty Acids, Omega-6; Fatty Acids, Unsaturated; Food, Fortified; Foot; Inflammation; Male; Rats; Rats, Wistar; Vitamin E

Topics: Acid Phosphatase; Adenosine Triphosphatases; Adrenal Glands; Animals; Anti-Inflammatory Agents; Catechols; Cathepsin D; Curcumin; Female; Glucuronidase; Ibuprofen; Inflammation; Male; Prostaglandins; Rats; Stimulation, Chemical