curcumin and Atherosclerosis

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

Cardiometabolic multimorbidity (CMM) is an increasingly significant global public health concern. It encompasses the coexistence of multiple cardiometabolic diseases, including hypertension, stroke, heart disease, atherosclerosis, and T2DM. A crucial component to the development of CMM is the disruption of endothelial homeostasis. Therefore, therapies targeting endothelial cells through multi-targeted and multi-pathway approaches hold promise for preventing and treatment of CMM. Curcumin, a widely used dietary supplement derived from the golden spice Carcuma longa, has demonstrated remarkable potential in treatment of CMM through its interaction with endothelial cells. Numerous studies have identified various molecular targets of curcumin (such as NF-κB/PI3K/AKT, MAPK/NF-κB/IL-1β, HO-1, NOs, VEGF, ICAM-1 and ROS). These findings highlight the efficacy of curcumin as a therapeutic agent against CMM through the regulation of endothelial function. It is worth noting that there is a close relationship between the progression of CMM and endothelial damage, characterized by oxidative stress, inflammation, abnormal NO bioavailability and cell adhesion. This paper provides a comprehensive review of curcumin, including its availability, pharmacokinetics, pharmaceutics, and therapeutic application in treatment of CMM, as well as the challenges and future prospects for its clinical translation. In summary, curcumin shows promise as a potential treatment option for CMM, particularly due to its ability to target endothelial cells. It represents a novel and natural lead compound that may offer significant therapeutic benefits in the management of CMM.

Topics: Atherosclerosis; Curcumin; Endothelial Cells; Humans; Multimorbidity; NF-kappa B; Phosphatidylinositol 3-Kinases; Spices

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

In recent years, epidemiological studies have suggested that metabolic disorders are nutritionally dependent. A healthy diet that is rich in polyphenols may be beneficial in the treatment of metabolic diseases such as polycystic ovary syndrome, metabolic syndrome, non-alcoholic fatty liver disease, cardiovascular disease, and, in particular, atherosclerosis. Curcumin is a polyphenol found in turmeric and has been reported to have antioxidant, anti-inflammatory, hepatoprotective, anti-atherosclerotic, and antidiabetic properties, among others. This review summarizes the influence of supplementation with curcumin on metabolic parameters in selected metabolic disorders.

Topics: Anti-Inflammatory Agents; Antioxidants; Atherosclerosis; Cardiovascular Diseases; Curcuma; Curcumin; Dietary Supplements; Female; Humans; Hypoglycemic Agents; Male; Metabolic Diseases; Non-alcoholic Fatty Liver Disease; Phytotherapy; Polycystic Ovary Syndrome

Curcumin, as a vegetative flavonoid, has a protective and therapeutic role in various adverse states such as oxidative stress and inflammation. Remedial properties of this component have been reported in the different chronic diseases including cancers (myeloma, pancreatic, breast, colorectal), vitiligo, psoriasis, neuropathic pains, inflammatory disorders (osteoarthritis, uveitis, ulcerative colitis, Alzheimer), cardiovascular conditions, and diabetes.Cardiovascular disorders include atherosclerosis and various manifestations of atherosclerosis such as stroke, and myocardial infarction (MI) is the leading cause of mortality globally. Studies have shown varying expressions of inflammatory and non-inflammatory chemokines and chemokine receptors in cardiovascular disease, which have been highlighted first in this review. The alteration in chemokines secretion and chemokine receptors has an essential role in the pathophysiology of cardiovascular disease. Chemokines as cytokines with low molecular weight (8-12 kDa) mediate white blood cell (WBC) chemotactic reactions, vascular cell migration, and proliferation that induce endothelial dysfunction, atherogenesis, and cardiac hypertrophy.Several studies reported that curcumin could be advantageous in the attenuation of cardiovascular diseases via anti-inflammatory effects and redress of chemokine secretion and chemokine receptors. We present these studies with a focus on two chemokines: CXCL8 (IL-8) and CCL2 (chemoattractant protein 1 or MCP-1). Future research will further elucidate the precise potential of curcumin on chemokines in the adjustment of cardiovascular system activity or curcumin chemokine-based therapies.

Topics: Atherosclerosis; Cardiovascular Diseases; Chemokine CCL2; Chemokines; Curcumin; Humans; Interleukin-8

Curcumin, a natural polyphenolic compound present in

Topics: Animals; Atherosclerosis; Curcumin; Humans; Signal Transduction

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

Numerous studies document an increased production of reactive oxygen species (ROS) with a subsequent decrease in nitric oxide (NO) bioavailability in different cardiovascular diseases, including hypertension, atherosclerosis, and heart failure. Many natural polyphenols have been demonstrated to decrease ROS generation and/or to induce the endogenous antioxidant enzymatic defense system. Moreover, different polyphenolic compounds have the ability to increase the activity/expression of endothelial nitric oxide synthase (eNOS) with a subsequent enhancement of NO generation. However, as a result of low absorption and bioavailability of natural polyphenols, the beneficial effects of these substances are very limited. Recent progress in delivering polyphenols to the targeted tissues revealed new possibilities for the use of polymeric nanoparticles in increasing the efficiency and reducing the degradability of natural polyphenols. This review focuses on the effects of different natural polyphenolic substances, especially resveratrol, quercetin, curcumin, and cherry extracts, and their ability to bind to polymeric nanoparticles, and summarizes the effects of polyphenol-loaded nanoparticles, mainly in the cardiovascular system.

Topics: Animals; Antioxidants; Atherosclerosis; Biological Availability; Biological Products; Cardiovascular System; Curcumin; Drug Compounding; Heart Failure; Humans; Hypertension; Nanocapsules; Nitric Oxide; Nitric Oxide Synthase Type III; Polymers; Polyphenols; Quercetin; Reactive Oxygen Species; Resveratrol

Monocytes and macrophages are important cells of the innate immune system that have diverse functions, including defense against invading pathogens, removal of dead cells by phagocytosis, antigen presentation in the context of MHC class I and class II molecules, and production of various pro-inflammatory cytokines and chemokines such as IL-1β, IL-6, TNF-α and MCP-1. In addition, pro-inflammatory (M1) and anti-inflammatory (M2) macrophages clearly play important roles in the progression of several inflammatory diseases. Therefore, therapies that target macrophage polarization and function by either blocking their trafficking to sites of inflammation, or skewing M1 to M2 phenotype polarization may hold clinical promise in several inflammatory diseases. Dietary-derived polyphenols have potent natural anti-oxidative properties. Within this group of polyphenols, curcumin has been shown to suppress macrophage inflammatory responses. Curcumin significantly reduces co-stimulatory molecules and also inhibits MAPK activation and the translocation of NF-κB p65. Curcumin can also polarize/repolarize macrophages toward the M2 phenotype. Curcumin-treated macrophages have been shown to be highly efficient at antigen capture and endocytosis via the mannose receptor. These novel findings provide new perspectives for the understanding of the immunopharmacological role of curcumin, as well as its therapeutic potential for impacting macrophage polarization and function in the context of inflammation-related disease. However, the precise effects of curcumin on the migration, differentiation, polarization and immunostimulatory functions of macrophages remain unknown. Therefore, in this review, we summarized whether curcumin can influence macrophage polarization, surface molecule expression, cytokine and chemokine production and their underlying pathways in the prevention of inflammatory diseases.

Topics: Alzheimer Disease; Animals; Antigen Presentation; Atherosclerosis; Cell Movement; Cell Polarity; Curcumin; Cytokines; Diet; Humans; Immunologic Factors; Infections; Liver Cirrhosis; Macrophages; Neoplasms; Obesity

Accumulation of macrophages within the artery wall is an eminent feature of atherosclerotic plaques. Macrophages are influenced by various plaque microenvironmental stimuli, such as oxidized lipids, cytokines, and senescent erythrocytes, and thereby polarize into two main phenotypes called proinflammatory M1 and anti-inflammatory M2 macrophages. In the hemorrhagic zones of atheroma, upon exposure to iron, sequestration of iron by M1 macrophages results in an uncontrolled proinflammatory phenotype impairing wound healing, while M2 macrophages phagocytose both apoptotic cells and senescent erythrocytes. M1 macrophages are prominent phenotype in the unstable plaques, in which plaque shoulder contains macrophages mainly present markers of M1 phenotype, whereas the fibrous cap encompassing the necrotic lipid core content macrophages expressed markers of both M1 and M2 subtypes. The abovementioned findings suggest macrophage modulation as a potent approach for atherosclerosis therapy. Curcumin is a polyphenol dietary derived from turmeric with numerous pharmacological activities. Recent in vitro and in vivo studies have indicated that curcumin exerted lipid-lowering effects, and also can modulate function of different macrophage subsets in various macrophage-involved diseases. The current review aimed to present role of macrophage subtypes in atherosclerosis development and progression, and to understand effect of curcumin on macrophage polarization and foam cell formation in the atherosclerosis lesions. Overall, we would address important targets for macrophage modulation in atherosclerotic plaques.

Topics: Animals; Atherosclerosis; Cell Plasticity; Cell Polarity; Curcumin; Cytokines; Humans; Hypolipidemic Agents; Macrophage Activation; Macrophages; Mice; Phenotype; Plaque, Atherosclerotic

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

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

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, a bioactive polyphenol, is a yellow pigment of the Curcuma longa (turmeric) plant. Curcumin has many pharmacologic effects including antioxidant, anti-carcinogenic, anti-obesity, anti-angiogenic and anti-inflammatory properties. Recently, it has been found that curcumin affects lipid metabolism, and subsequently, may alleviate hyperlipidemia and atherosclerosis. Plasma HDL cholesterol (HDL-C) is an independent negative risk predictor of cardiovascular disease (CVD). However, numerous clinical and genetic studies have yielded disappointing results about the therapeutic benefit of raising plasma HDL-C levels. Therefore, research efforts are now focused on improving HDL functionality, independent of HDL-C levels. The quality of HDL particles can vary considerably due to heterogeneity in composition. Consistent with its complexity in composition and metabolism, a wide range of biological activities is reported for HDL, including antioxidant, anti-glycation, anti-inflammatory, anti-thrombotic, anti-apoptotic and immune modulatory activities. Protective properties of curcumin may influence HDL functionality; therefore, we reviewed the literature to determine whether curcumin can augment HDL function. In this review, we concluded that curcumin may modulate markers of HDL function, such as apo-AI, CETP, LCAT, PON1, MPO activities and levels. Curcumin may subsequently improve conditions in which HDL is dysfunctional and may have potential as a therapeutic drug in future. Further clinical trials with bioavailability-improved formulations of curcumin are warranted to examine its effects on lipid metabolism and HDL function.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Antioxidants; Atherosclerosis; Curcuma; Curcumin; Dyslipidemias; Humans; Lipoproteins, HDL

Atherosclerosis (AS) is a systemic cardiovascular disease with complicated pathogenesis involving oxidative stress, endothelial dysfunction and chronic inflammation. Increasing lines of evidence have questioned the statins-dominated treatment for AS, including their dangerous side-effects such as the breakdown of muscle when taken in larger doses. A multifaceted approach that addresses all major risk factors or pathological targets may provide an ideal treatment for AS. Studies of the herbal remedies on the prevention and treatment of AS have received much attention in recent years. This review summarizes some important experimental findings regarding their mechanisms of action on AS. Using the pre-set PUBMED searching syntax and inclusion criteria, representative citations published in English concerning the experimental studies of 14 herbal materials were included. We found that many extracts and (or) single compounds from these herbal materials, such as Salvia miltiorrhiza, Curcuma longa, Rheum undulatum and Panax notoginseng, could regulate multiple key targets involved in the initiation and propagation of AS. Some important findings about the effects of herbal formulations on AS were also reviewed. Given the complicated nature of AS and the holistic, combinational approach of herbal remedies, we propose that mixed herbal preparations with multiple active ingredients may be preferable for the prevention and treatment of AS. Further rigorously designed pharmacological evaluation and multi-centred clinical trials are warranted.

Topics: Atherosclerosis; Curcuma; Humans; Panax notoginseng; Phytotherapy; Plant Extracts; Rheum; Salvia miltiorrhiza

Angiogenesis, the formation of new blood vessels from preexisting vascular network is a driving force of organ development in ontogeny, is necessary for ovulation and hair growth, and is prerequisite for proper wound healing. It is also a critical mechanism of numerous diseases, the most important of which are cancer and atherosclerosis. Therefore, modulation of angiogenesis is considered as therapeutic strategies of great importance for human health. Numerous bioactive plant compounds, often referred to as nutraceuticals are recently tested for the potential clinical applications. Among the most frequently studied are resveratrol, a polyphenol present in red-wine and grape-seed, epigallocatechin-3-gallate (EGCG) from green tea and curcumin from Curcuma longa. It is also possible that components of other plants, including the constituents of local food diet may find application for modulation of angiogenesis, provided that their effectiveness will be confirmed in controlled, scientifically validated trials.

Topics: Angiogenesis Inhibitors; Animals; Atherosclerosis; Catechin; Curcumin; Dietary Supplements; Flavonoids; Humans; Neoplasms; Neovascularization, Pathologic; Phenols; Polyphenols; Resveratrol; Stilbenes; Vascular Endothelial Growth Factor A

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)

Cardiovascular disease (CVD) is the leading cause of death in patients with non-alcoholic fatty liver disease (NAFLD). Curcumin has been shown to exert glucose-lowering and anti-atherosclerotic effects in type 2 diabetes. Hence, we investigated curcumin's effects on atherogenesis markers, fatty liver, insulin resistance, and adipose tissue-related indicators in patients with NAFLD. In this secondary analysis of a 12-week randomized controlled trial, fifty-two patients with NAFLD received lifestyle modification. In addition, they were randomly allocated to either the curcumin group (1.5 g/day) or the matching placebo. Outcome variables (assessed before and after the study) were: the fatty liver index (FLI), hepatic steatosis index (HSI), fatty liver score (FLS), BMI, age, ALT, TG score (BAAT), triglyceride glucose (TyG) index, Castelli risk index-I (CRI-I), Castelli risk index-II (CRI-II), TG/HDL-C ratio, atherogenic coefficient (AC), atherogenic index of plasma (AIP), lipoprotein combine index (LCI), cholesterol index (CHOLINDEX), lipid accumulation product (LAP), body adiposity index (BAI), visceral adiposity index (VAI), metabolic score for visceral fat (METS-VF), visceral adipose tissue (VAT), and waist-to-height ratio (WHtR) values. The TyG index decreased in the curcumin group and increased in the placebo group, with a significant difference between the groups (

Topics: Atherosclerosis; Body Mass Index; Cardiovascular Diseases; Curcumin; Diabetes Mellitus, Type 2; Glucose; Humans; Life Style; Non-alcoholic Fatty Liver Disease; Triglycerides

COPD is mainly caused by tobacco smoking and is associated with a high frequency of coronary artery disease. There is growing recognition that the inflammation in COPD is not only confined to the lungs but also involves the systemic circulation and can impact nonpulmonary organs, including blood vessels. α1-antitrypsin-low-density lipoprotein (AT-LDL) complex is an oxidatively modified LDL that accelerates atherosclerosis. Curcumin, one of the best-investigated natural products, is a powerful antioxidant. However, the effects of curcumin on AT-LDL remain unknown. We hypothesized that Theracurmin(®), a highly absorptive curcumin with improved bioavailability using a drug delivery system, ameliorates the inflammatory status in subjects with mild COPD.. This is a randomized, double-blind, parallel-group study. Subjects with stages I-II COPD according to the Japanese Respiratory Society criteria were randomly assigned to receive 90 mg Theracurmin(®) or placebo twice a day for 24 weeks, and changes in inflammatory parameters were evaluated.. There were no differences between the Theracurmin(®) and placebo groups in terms of age, male/female ratio, or body mass index in 39 evaluable subjects. The percent changes in blood pressure and hemoglobin A1c and LDL-cholesterol, triglyceride, or high-density lipoprotein-cholesterol levels after treatment were similar for the two groups. However, the percent change in the AT-LDL level was significantly (P=0.020) lower in the Theracurmin(®) group compared with the placebo group.. Theracurmin(®) reduced levels of atherosclerotic AT-LDL, which may lead to the prevention of future cardiovascular events in mild COPD subjects.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; alpha 1-Antitrypsin; Anti-Inflammatory Agents; Atherosclerosis; Biological Availability; Biomarkers; Curcumin; Double-Blind Method; Down-Regulation; Drug Administration Schedule; Drug Compounding; Female; Gastrointestinal Absorption; Humans; Japan; Lipoproteins, LDL; Male; Middle Aged; Pulmonary Disease, Chronic Obstructive; Time Factors; Treatment Outcome; Young Adult

Curcumin is a phytocompound found in the root of turmeric, a common herbal ingredient in many Asian cuisines. The compound contains anti-inflammatory activity, which is mediated through an up-regulation of adiponectin and reduction of leptin. Consumption of curcumin was shown to prevent some deteriorative conditions caused by inflammation, such as ulcerative colitis, rheumatoid arthritis and esophagitis, and so on. Inflammation-associated cardiovascular conditions such as atherosclerosis are common in diabetes patients. The anti-inflammation effect of curcumin might be beneficial to prevent such condition in these patients. We aim to evaluate an antiatherosclerosis effect of curcumin in diabetes patients. Effects of curcumin on risk factors for atherosclerosis were investigated in a 6-month randomized, double-blinded and placebo-controlled clinical trial that included subjects diagnosed with type 2 diabetes. An atherosclerosis parameter, the pulse wave velocity, and other metabolic parameters in patients treated with placebo and curcumin were compared. Our results showed that curcumin intervention significantly reduced pulse wave velocity, increased level of serum adiponectin and decreased level of leptin. These results are associated with reduced levels of homeostasis model assessment-insulin resistance, triglyceride, uric acid, visceral fat and total body fat. In summary, a 6-month curcumin intervention in type 2 diabetic population lowered the atherogenic risks. In addition, the extract helped to improve relevant metabolic profiles in this high-risk population.

Topics: Atherosclerosis; Curcumin; Diabetes Mellitus, Type 2; Double-Blind Method; Female; Humans; Male; Middle Aged; Patient Compliance; Placebos

Conjugate drugs are evolving into potent techniques in the drug development process for enhancing the biopharmaceutical, physicochemical, and pharmacokinetic properties. Atorvastatin (AT) is the first line of treatment for coronary atherosclerosis; however its therapeutic efficacy is limited because of its poor solubility and fast pass metabolism. Curcumin (CU) is evidenced in several crucial signaling pathways linked to lipid regulation and inflammation. To enhance the therapeutic efficacy and physical properties of AT and CU, a new conjugate derivative (AT-CU) was synthesized and assessed by in silico, in vitro characterizations, and in vivo efficacy through mice model. Although the biocompatibility and biodegradability of Polylactic-co-Glycolic Acid (PLGA) in nanoparticles are well documented, burst release is a common issue with this polymer. Hence the current work used chitosan as a drug release modifier to the PLGA nanoparticles. The chitosan-modified PLGA AT-CU nanoparticles were prepaid by single emulsion and solvent evaporation technique. With raising the concentration of chitosan the particle size grew from 139.2 nm to 197.7 nm, the zeta potential rose from -20.57 mV to 28.32 mV, and the drug encapsulation efficiency improved from 71.81% to 90.57%. At 18 h, the burst release of AT-CU from PLGA nanoparticles was seen, hitting abruptly 70.8%. For chitosan-modified PLGA nanoparticles, the burst release pattern was significantly reduced which could be due to the adsorption of the drug on the surface of chitosan. The efficiency of the ideal formulation i.e F4 (chitosan/PLGA = 0.4) in treating atherosclerosis was further strongly evidenced by in vivo investigation.

Topics: Animals; Atherosclerosis; Atorvastatin; Chitosan; Copper; Curcumin; Drug Carriers; Glycols; Mice; Nanoparticles; Particle Size; Polylactic Acid-Polyglycolic Acid Copolymer

To explore the sesquiterpenoids in

Topics: Atherosclerosis; Cholesterol; Curcuma; Foam Cells; Lipopolysaccharides; Lipoproteins, LDL; Monocyclic Sesquiterpenes; Sesquiterpenes

Elevated levels of plasma low-density lipoprotein cholesterol (LDL-C) are causally related to atherosclerotic cardiovascular disease. Enhancing the removal of LDL particles from the plasma, mainly by the liver, is the most efficient strategy for reducing LDL-C and the ensuing atherosclerosis. In this context, polyphenolic compounds like curcumin have generated interest owing to their lipid-modifying capacity. The promising effect of curcumin has been studied in attenuating atherosclerosis (in experimental models), and correcting dyslipidemia (in clinical studies). The underlying mechanisms of the effects of curcumin are relatively unknown, and the impact of curcumin on hepatic LDL uptake warrants further investigations. Here, we present a protocol to assess the effects of curcumin on LDL uptake in hepatocytes.

Topics: Atherosclerosis; Cholesterol, LDL; Curcumin; Hepatocytes; Humans; Liver

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

Studies have shown that cadmium (Cd) exposure primarily occurs through diet, and Cd ingestion is a risk factor for atherosclerosis (AS). However, the underlying mechanism remains unclear. As a target organ, the gastrointestinal tract may play a key role in Cd-induced AS. Additionally, as curcumin is insoluble in water but stable in the stomach of acidic pH, it may play regulative roles in the gut.. We assess the effect of Cd exposure on gut flora, trimethylamine-N-oxide (TMAO) metabolism and macrophage polarization, further investigate whether curcumin protects against Cd-induced AS by remodeling gut microbiota.. The results of 16 S rRNA sequencing show that Cd exposure causes diversity reduction and compositional alteration of the microbial community, resulting in the increasing TMAO synthesis, the imbalance of lipid metabolism, and the M1-type macrophage polarization in the mouse model (ApoE. We first demonstrate that Cd exposure worsens the progression of AS via intestinal flora imbalance and increased TMAO synthesis. Curcumin was verified as a potential novel intervention for preventing Cd-induced AS via remodeling gut microbiota. This study elucidates a new approach for treating AS in regions with significant Cd exposure.

Topics: Animals; Apolipoproteins E; Atherosclerosis; Cadmium; Curcumin; Gastrointestinal Microbiome; Macrophages; Methylamines; Mice; Oxides; Water

Peptide-based high-density lipoprotein (pHDL) structurally and functionally resembles the natural HDL as anti-atherosclerosis (AS) therapies. Since pHDL contains a large hydrophobic core, this study aims to evaluate the potentials of pHDL as a hydrophobic drug carrier and the efficiency of drug-loaded pHDL in the control of AS.. The pHDL encapsulation of hydrophobic components from natural plants, including curcumin (Cur) and tanshinone IIA (TanIIA), was achieved using one-step microfluidics. Then, morphological features and loading efficiencies of pHDL-Cur and pHDL-TanIIA were determined by TEM and high-performance liquid chromatography (HPLC), respectively. Taking the fluorescence advantage of Cur, localizations of loaded Cur in pHDL were investigated by fluorescence quenchers, and recruitments of Cur to AS plaques were assessed with ex vivo imaging. Based on anti-inflammatory properties of TanIIA, pHDL-TanIIA was accordingly developed to evaluate the anti-AS effects through examinations of plasma lipid parameters and pathological alterations of plaque-associated regions.. Both lipophilic Cur and TanIIA can be efficiently loaded into pHDL carriers. The resultant pHDL-Cur and pHDL-TanIIA inherit the homogeneous nano-disk structure of pHDL. By using pHDL-Cur, the encapsulated hydrophobics are tracked in the core of pHDL, and incorporations of Cur with pHDL vehicles greatly improve the bioavailability and association of Cur with AS plaques. Moreover, when loaded with TanIIA, which has established its role in anti-AS as an anti-inflammatory candidate, synergistic effects in reducing AS lesions and improving pathological alterations of main organs related to AS were achieved.. The pHDL system could potentially be applied for both imaging and therapy in animal models of AS. Benefits of pHDL-based drug delivery will potentially extend the application scenarios of bioactive chemicals from natural plants which are underutilized due to features like low bioavailability and facilitate the clinical translation of synthetic HDL therapies in HDL-associated disorders, including but not limited to AS.

Topics: Animals; Atherosclerosis; Biological Availability; Curcumin; Drug Carriers; Peptides

Excessive free fatty acid- (FFA-) induced endothelial lipotoxicity is involved in the pathogenesis of atherosclerosis. Endoplasmic reticulum (ER) stress is mechanistically related to endothelial lipotoxicity. Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) is the major oxidatively modified low-density lipoprotein (OxLDL) receptor in endothelial cells and is highly abundant in atherosclerotic lesions. Curcumin reduces the LOX-1 expression; however, the mechanism underlying this effect remains unknown. In the current study, we explored whether curcumin ameliorates palmitic acid- (PA-) induced endothelial lipotoxicity and LOX-1 upregulation by reducing ER stress in human umbilical vein endothelial cells (HUVECs). We built endothelial lipotoxicity in vitro and found that LOX-1 was upregulated after PA stimulation, during which ER stress played an important role. Next, we observed that curcumin substantially alleviated PA-induced lipotoxicity by restoring cell viability, increasing angiogenesis, and decreasing lipid deposition. Furthermore, LOX-1 upregulation in HUVECs was blocked by curcumin, possibly via ER stress suppression. Overall, our findings demonstrated that curcumin alleviates endothelial lipotoxicity and LOX-1 upregulation, and ER stress inhibition may play a critical role in this effect.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Atherosclerosis; Cell Survival; Cells, Cultured; Curcumin; Endoplasmic Reticulum Stress; Enzyme Inhibitors; Human Umbilical Vein Endothelial Cells; Humans; Palmitic Acid; Scavenger Receptors, Class E

Phenotypic switching is the main cause of the abnormal proliferation and migration of vascular smooth muscle cells (VSMCs). We previously showed that Daxx exerted negative regulatory effect on AngII-induced VSMC proliferation and migration. However, the function of Daxx in VSMC phenotype switching remained unknown. Nicotinate-curcumin (NC) is an esterification derivative of niacin and curcumin that can prevent the formation of atherosclerosis. We found that NC significantly decreased AngII-induced VSMC phenotype switching. Furthermore, NC significantly inhibited AngII-induced cell proliferation and migration. Moreover, NC upregulated Daxx expression and regulated the PTEN/Akt signaling pathway. We concluded that NC inhibited AngII-induced VSMC phenotype switching by regulating the PTEN/Akt pathway, and through a mechanism that might be associated with the upregulation of Daxx expression.

Topics: Atherosclerosis; Cell Movement; Cell Proliferation; Cells, Cultured; Co-Repressor Proteins; Curcumin; Humans; Molecular Chaperones; Muscle, Smooth, Vascular; Myocytes, Smooth Muscle; Niacin; Phenotype; Proto-Oncogene Proteins c-akt; PTEN Phosphohydrolase; Signal Transduction; Up-Regulation

Curcumin has been shown to have beneficial effects on pathogenic factors involved in the development of atherosclerosis. The aim of this study was to assess the effects of curcumin phytosomes on atherosclerosis induced by high-fat diet in rabbits. A total of 16 adult male New Zealand white rabbits (1.8-2 kg) were fed with a diet containing 0.5% cholesterol for 4 weeks. The rabbits were randomly divided into four groups of four animals each. Group I orally received PBS for 4 weeks. Group II animals were treated with curcumin-phosphatidylcholine solid state dispersion (Meriva®, Indena, Italy) suspended in normal saline at doses equivalent to 100 mg/kg of curcuminoids per day p.o., for 4 weeks. Groups III and IV were treated with curcumin-phosphatidylserine solid state dispersion (Meriserin®, Indena, Italy) suspended in normal saline at doses equivalent to 10 and 100 mg/kg of curcuminoids, respectively, per day p.o., for 4 weeks. For atherosclerosis evaluation, histological examinations on aortic arch section were performed. Blood samples were obtained to determine lipid profile and high-sensitivity C-reactive protein (hs-CRP) levels. Curcumin-phosphatidylserine (100 mg/kg) therapy resulted in a significant reduction in grading of atherosclerotic plaque and intima/media thickness ratio (P < 0.05) and decreased presence of inflammatory cells in the atherosclerotic lesions compared to the control group. However, no significant differences were observed between the curcumin-phospholipid preparations and the control group regarding lipid profile and hs-CRP levels. Results of the present study revealed an atheroprotective effect of curcumin-phosphatidylserine (100 mg/kg) solid dispersion as revealed by a reduction in the development of atherosclerotic lesions.

Topics: Animals; Atherosclerosis; Curcumin; Diet, High-Fat; Italy; Male; Plaque, Atherosclerotic; Rabbits

Orally administered curcumin has been found to have a moderate therapeutic effect on dyslipidemia and atherosclerosis. The present study was conducted to determine lipid-modulating and antiatherosclerosis effects of injectable curcumin in the rabbit model of atherosclerosis induced by a high cholesterol diet (HCD). New Zealand white male rabbits were fed on a normal chow enriched with 0.5% (w/w) cholesterol for 8 weeks. Atherosclerotic rabbits were randomly divided into three groups, including a control group receiving intravenous (IV) injection of the saline buffer, two treatment groups receiving IV administration of the injectable curcumin at low (1 mg/kg/week) and high (10 mg/kg/week) over 4 weeks. Plasma lipid parameters, including low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), and total cholesterol (TC) were measured. Aortic arch atherosclerotic lesions were assessed using hematoxylin and eosin (H&E) staining. The low dose of curcumin significantly reduced plasma levels of TC, LDL-C, and TG by -14.19 ± 5.19%, -6.22 ± 1.77%, and - 29.84 ± 10.14%, respectively, and increased HDL-C by 14.05 ± 6.39% (p < 0.05). High dose of curcumin exerted greater lipid-modifying effects, in which plasma levels of TC, LDL-C, and TG were significantly (p < 0.05) decreased by -56.59 ± 10.22%, -44.36 ± 3.24%, and - 25.92 ± 5.57%, respectively, and HDL-C was significantly increased by 36.24 ± 12.5%. H&E staining showed that the lesion severity was lowered significantly in the high dose (p = 0.03) but not significantly (p > 0.05) in the low-dose curcumin groups, compared to control rabbits. The median (interquartile range) of plaque grades in the high dose and low dose, and control groups was found to be 2 [2-3], 3 [2-3], and 4 [3-4], respectively. The injectable curcumin could significantly improve dyslipidemia and alleviate atherosclerotic lesion in HCD-induced atherosclerotic rabbits.

Topics: Animals; Atherosclerosis; Cholesterol; Cholesterol, HDL; Curcumin; Male; Rabbits; Triglycerides

To seek out the effect of curcumin on cholesterol efflux in THP-1 macrophages and clarify its specific mechanism.. THP-1 macrophages were cultured with curcumin at different concentrations, followed by detection of the toxicity of curcumin to cells utilizing CCK-8 assay. Following culturing with serum-free ox-LDL, THP-1 macrophages were transfected with mi-miR-125a-5p, or in-miR-125a-5p, or pcDNA3.1-SIRT6, or si-SIRT6 for 24 hr, prior to treatment with curcumin at different concentrations. Oil red O staining was applied to examine the formation rate of foam cells, the kits were used for measuring intracellular lipid content of THP-1 macrophages, and the fluorescence detection kit for observing the cholesterol efflux rate. The expressions of miR-125a-5p, SIRT6, and ABCA1 were assayed by qRT-PCR and Western blot. ELISA was adopted to assess the contents of TNF-α, IL-6, and MCP-1. The interaction between miR-125a-5p and SIRT6 was evaluated by dual-luciferase reporter gene assay.. The optimal dosage of curcumin could reduce foam cell formation and intracellular lipid content, and promote cholesterol efflux in THP-1 macrophages. Meanwhile, curcumin markedly suppressed the expression of miR-125a-5p and upregulated the expression of SIRT6. MiR-125a-5p negatively targeted SIRT6. Overexpression of SIRT6 partially reversed the inhibition role of miR-125a-5p mimic in the biological function of curcumin. Silencing of SIRT6 could partially reverse the effect of the miR-125a-5p inhibitor on the biological function of curcumin.. urcumin could promote cholesterol efflux of THP-1 macrophages through miR-125a-5p/SIRT6 axis and regulate the expression of ABCA1.

Topics: Atherosclerosis; ATP Binding Cassette Transporter 1; Cholesterol; Curcumin; Cytokines; Humans; Lipoproteins, LDL; Macrophages; MicroRNAs; Sirtuins; THP-1 Cells

Atherosclerosis (AS) is a chronic progressive inflammatory disease and a leading cause of death worldwide. Being a novel adipokine, chemerin is reported to be positively correlated with the severity of AS, yet its underlying mechanisms in AS remains elusive. It is well-known that AS development is significantly attributed to abnormal proliferation and migration of vascular smooth muscle cells (VSMCs). Therefore, we investigated the role of the chemerin / chemokine-like receptor 1 (CMKLR1, chemerin receptor) signaling, and the potential therapeutic effect of curcumin in VSMCs proliferation and migration during AS by establishing a high fat diet (HFD) mouse model. We found that CMKLR1 was highly expressed in HFD-induced AS tissues and that its expression level was positively correlated with aortic proliferation. Knockdown of CMKLR1 significantly inhibited VSMCs proliferation and migration, as evidenced by the EdU-incorporation assay, wound healing assay, and the induction of proliferating cell nuclear antigen (PCNA) and matrix metalloproteinase-9 (MMP-9) expression. Furthermore, we discovered that Lipocalin-2 (LCN2) acts as a key factor involved in CMKLR1-mediated VSMCs proliferation and migration via the p38 / MAPK and Wnt / β-catenin signaling pathways, and we demonstrated that curcumin inhibits VSMCs proliferation and migration by inhibiting chemerin / CMKLR1 / LCN2, thereby reducing AS progression. Our findings suggest that chemerin / CMKLR1 activation promotes the development of AS; hence, targeting the chemerin / CMKLR1 / LCN2 signaling pathway may be a reasonable treatment modality for AS.

Topics: Animals; Aorta; Apolipoproteins E; Atherosclerosis; Cell Movement; Cell Proliferation; Chemokines; Curcumin; Diet, High-Fat; Gene Knockdown Techniques; Intercellular Signaling Peptides and Proteins; Lipocalin-2; Male; Mice, Knockout; Muscle, Smooth, Vascular; Myocytes, Smooth Muscle; Plaque, Atherosclerotic; Receptors, Chemokine; Signal Transduction

Vascular smooth muscle cells (VSMCs) are becoming a hot spot and target of atherosclerosis research. This study aimed to observe the specific effects of curcumin (CUR)-mediated photodynamic therapy (CUR-PDT) on oxidized low-density lipoprotein (ox-LDL)-treated VSMCs and confirm whether these effects are mediated by autophagy. In this study, the mouse aortic smooth muscle cell line and A7r5 cell lines were used for parallel experiments. VSMC viability was evaluated by Cell Counting Kit-8 assay. VSMCs were treated with ox-LDL to establish a model of atherosclerosis in vitro. The autophagy level and the expression of proteins related to phenotypic transformation were detected by western blotting. The migration ability of the cells was detected by using transwell assay. The presence of intracellular lipid droplets was detected by Oil Red O staining. The results showed that VSMCs transformed from the contraction phenotype to the synthetic phenotype when stimulated by ox-LDL, during which autophagy was inhibited. However, CUR-PDT treatment significantly promoted the level of autophagy and inhibited the process of phenotypic transformation induced by ox-LDL. In addition, ox-LDL significantly promoted VSMC migration and increased the number of lipid droplets, whereas CUR-PDT treatment significantly reduced the ox-LDL-induced increase in the migration ability of, and lipid droplet numbers in, VSMCs. When the VSMCs were pretreated with the autophagy inhibitor 3-methyladenine for 24 hours, the effects of CUR-PDT were reversed. Therefore, our study indicated that CUR-PDT can inhibit the phenotypic transformation, migration, and foaming of ox-LDL-treated VSMCs by inducing autophagy.

Topics: Animals; Atherosclerosis; Autophagy; Cell Line; Cell Movement; Cell Plasticity; Cell Transdifferentiation; Curcumin; Foam Cells; Lipoproteins, LDL; Mice; Muscle, Smooth, Vascular; Myocytes, Smooth Muscle; Photochemotherapy; Photosensitizing Agents; Rats; Treatment Outcome

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

Previous studies have shown that curcumin (Cur) induced by ultrasound has protective effects on atherosclerosis even if low bioavailability of the Cur. The enhancement of bioavailability of the Cur further improved the curative effect of sonodynamic therapy (SDT) on atherosclerosis through nanotechnology. Nanosuspensions as a good drug delivery system had obvious advantages in increasing the solubility and improving the effectiveness of insoluble drugs. The aim of this study was to develop curcumin nanosuspensions (Cur-ns) which used polyvinylpyrrolidone (PVPK30) and sodium dodecyl sulfate (SDS) as stabilizers to improve poor water solubility and bioavailability of the Cur. And then the therapeutic effects of Cur-ns-SDT on atherosclerotic plaques and its possible mechanisms would be investigated and elucidated. Cur-ns with a small particle size has been successfully prepared and the data have confirmed that Cur-ns could be more easily engulfed into RAW264.7 cells than free Cur and accumulated more under the stimulation of the ultrasound. Reactive oxygen species (ROS) inside RAW264.7 cells after SDT led to the decrease of mitochondrial membrane potential (MMP) and the higher expression of cleaved caspase-9/3. The results of in vivo experiments showed that Cur-ns-SDT reduced the level of total cholesterol (TC) and low density lipoprotein (LDL) and promoted the transformation from M1 to M2 macrophages, relieved atherosclerosis syndrome. Therefore, Cur-ns-SDT was a potential treatment of anti-atherosclerosis by enhancing macrophages apoptosis through mitochondrial pathway and inhibiting the progression of plaques by interfering with macrophages polarization.

Topics: Administration, Oral; Animals; Apoptosis; Atherosclerosis; Biological Availability; Cholesterol; Combined Modality Therapy; Curcumin; Disease Models, Animal; Drug Delivery Systems; Humans; Lipoproteins, LDL; Male; Membrane Potential, Mitochondrial; Mice; Mice, Knockout, ApoE; Nanoparticles; Particle Size; Pharmaceutical Vehicles; Povidone; RAW 264.7 Cells; Reactive Oxygen Species; Sodium Dodecyl Sulfate; Theranostic Nanomedicine; Ultrasonic Therapy

Curcumin (Cur) is a hydrophobic polyphenol compound derived from the rhizome of the herb Curcuma longa. Cur has a wide spectrum of biological and pharmacological activities. It has been shown that human cytomegalovirus (HCMV) infection was an important risk factor for atherosclerosis (AS) and Cur exhibited an outstanding anti-HCMV effect. However, anti-AS effects of Cur remain unclear when HCMV infected endothelial cells.. This study will investigate the anti-AS activities and mechanism of Cur,when HCMV infected in vivo and in vitro.. As our results showed that Cur inhibited CMV replication and proliferation, reduced the intracellular ROS overproduction, decreased the release of inflammatory cytokines, down-regulated the level of HMGB1-TLRS-NF-κB signaling pathway-related proteins in vitro experiments. Cur reduced the serum levels of LDL-C, TC and TG, significantly decreased the formation of atherosclerotic plaque in the aorta, reduced the lipid deposition in liver and inflammatory damage in heart, lung and kidney in vivo experiments.. This study showed that Cur prevent AS progression by inhibiting CMV activity and CMV-induced HMGB1-TLRS-NF-κB signaling pathway.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Apolipoproteins E; Atherosclerosis; Curcuma; Curcumin; Cytokines; Cytomegalovirus; Endothelial Cells; Human Umbilical Vein Endothelial Cells; Humans; Male; Mice; Mice, Transgenic; NF-kappa B; Plant Extracts; Plaque, Atherosclerotic; Signal Transduction

Although curcumin possesses anti-atherogenic and anti-inflammatory properties, its application is limited because of its low aqueous solubility and poor oral bioavailability. Recently, our group synthesized a novel linear-dendrimer methoxy-poly (ethylene glycol)-b-poly(ε-caprolactone) copolymer nanoparticle loading curcumin (Cur-NPs) which could improve solubility and release property of curcumin. In the present study, we further evaluated its anti-atherosclerotic effect in apolipoprotein E

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Apolipoproteins E; Atherosclerosis; Curcumin; Gene Deletion; Male; Mice; Nanoparticles

Allergic asthma and atherosclerosis represent different directions of inflammatory responses of CD4. We aimed to investigate the roles of curcumin in asthma-accelerated atherosclerosis plaque formation, and the change of CD4. Six to eight-week-old apolipoprotein E. The accelerated atherosclerosis was induced by allergic asthma accompanied by increased T helper cell (Th)2 and Th17 cells and decreased regulatory T cells (Tregs) in the spleen. After the 8-week treatment with curcumin, the lesion areas in the aortic root in asthmatic mice significantly improved, and the elevated Th2 and Th17 cells significantly decreased, but Tregs markedly increased. Although curcumin treatment markedly reduced the interleukin (IL)-4 and IL-13 in serum and spleen, the elevated IL-17A did not decrease. Moreover, Th1 cells showed no significant change between different groups. The mRNA expression levels of M1 macrophage-related inflammatory factors IL-6, iNOS and IL-1β were markedly elevated in the spleens of asthmatic mice, but significantly decreased after the 8-week treatment with curcumin.. Curcumin ameliorated the aggravation of atherosclerotic lesions and stabilised plaque by modulating the balance of Th2/Tregs in asthmatic apoE

Topics: Animals; Asthma; Atherosclerosis; Curcumin; Interleukins; Mice; Mice, Inbred C57BL; Mice, Knockout, ApoE; Ovalbumin; Plaque, Atherosclerotic; T-Lymphocytes, Regulatory; Th1 Cells; Th17 Cells; Th2 Cells

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 potential usage of curcumin in diverse human diseases has been widely studied, including arteriosclerosis (AS). This study focused on investigating the relationship between curcumin and AS-associated microRNA, which may provide a better understanding of curcumin in a different mechanism. Human microvascular endothelial HMEC-1 cells were treated by curcumin alone or oxidized low-density lipoprotein (ox-LDL) plus curcumin, after which the following parameters were analyzed: cell viability, migration, and the expression of AS-associated factors. The regulatory effects of curcumin on miR-126 and signaling pathways involved in AS were then studied. Further, an animal model of AS was stimulated by feeding rabbits with 1% cholesterol diet. The effects of curcumin on the animal model were explored. We found that curcumin treatment significantly reduced HMEC-1 cells viability, migration, and the protein levels of MMP-2, MMP-9, and vascular endothelial growth factor (VEGF) in the presence or absence of ox-LDL. Meanwhile, the expression of VEGFR1 and VEGFR2 was repressed by curcumin. miR-126 was upregulated by curcumin. The abovementioned effects of curcumin on HMEC-1 cells were all attenuated when miR-126 was silenced. And also, VEGF was a target gene of miR-126, and curcumin could inhibit the activation of PI3K/AKT JAK2/STAT5 signaling pathways via miR-126. The effects of curcumin and its regulation on miR-126 and VEGF were confirmed in the animal model of AS. To sum up, curcumin exerted potent anti-AS property possibly via upregulating miR-126 and thereby inhibiting PI3K/AKT and JAK2/STAT5 signaling pathways.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Atherosclerosis; Cell Line; Cell Movement; Cell Survival; Curcumin; Endothelial Cells; Humans; MicroRNAs; Rabbits; Signal Transduction; Up-Regulation; Vascular Endothelial Growth Factor A

Topics: Animals; Apolipoproteins E; Atherosclerosis; Curcumin; Humans; Intercellular Adhesion Molecule-1; Interleukin-1beta; Male; Mice; Mice, Knockout; Toll-Like Receptor 4; Tumor Necrosis Factor-alpha

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

Atorvastatin known to be a potential inhibitor of HMG-CoA reductase involved in the synthesis of cholesterol. It is touted as miracle drug due to its profound effect in decreasing the low-density lipoproteins in blood. Unfortunately, the high dosage used poses side-effects relatively in comparison to other statins. On the other hand, curcumin has a diverse therapeutic potential in health and disease. However, the poor aqueous solubility and low bioavailability hinders the therapeutic potential of it when administrated orally. Therefore, it was thought to minimise the frequency of atorvastatin doses to avoid the possibility of drug resistance and also to overcome the limitations of curcumin for desirable therapeutic effects by using nanocarriers in drug delivery. In this investigation, synergistic effect of atorvastatin and curcumin nanocarriers was encapsulated by chitosan polymer. The chitosan nanocarriers prepared by ionic gelation method were characterised for their particle size, zeta potential, and other parameters. The drug-loaded nanocarriers exhibited good encapsulation efficiency (74.25%) and showed a slow and sustained release of atorvastatin and curcumin 60.36 and 61.44%, respectively, in a span of 48 h. The drug-loaded nanocarriers found to be haemocompatible and qualified for drug delivery in atherosclerosis.

Topics: Administration, Oral; Anticholesteremic Agents; Atherosclerosis; Atorvastatin; Chitosan; Curcumin; Delayed-Action Preparations; Diffusion; Drug Combinations; Drug Compounding; Humans; Nanocapsules; Particle Size

Topics: Administration, Oral; Angiotensin II; Angiotensinogen; Animals; Atherosclerosis; Chlorogenic Acid; Commiphora; Curcumin; Diet, High-Fat; Dietary Supplements; Fatty Acid-Binding Proteins; Gene Expression Regulation; Inulin; Lipid Metabolism; Male; Mice; Mice, Inbred C57BL; Neoplasm Proteins; Non-alcoholic Fatty Liver Disease; Plant Extracts; Plant Gums; RNA, Messenger; Silymarin; Suppressor of Cytokine Signaling 3 Protein

β-Elemene is a major bioactive sesquiterpenoids compound isolated from the essential oils of Curcuma Wenyujin, a Chinese medicinal herb that treats tumor in clinics. However anti-atherosclerotic effects of β-elemene have not been fully investigated in vivo. The objective of this study is to further elucidate the anti-atherosclerotic activities of β-elemene in ApoE

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Apolipoproteins E; Atherosclerosis; Curcuma; Endothelium, Vascular; Human Umbilical Vein Endothelial Cells; Humans; Lipids; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Nitrates; Nitric Oxide; Nitric Oxide Synthase Type III; Nitrites; Oxidative Stress; Reactive Oxygen Species; Sesquiterpenes

L3, an analog of curcumin, is a compound isolated from a traditional Chinese medicine Turmeric. In this paper, we aims to explore the efficacy of L3 on diabetic atherosclerosis and the related mechanism. The effect of L3 was studied on glucose and lipid metabolism, antioxidant status, atherosclerosis-related indexes and pathological changes of main organs in the mice model of diabetes induced by streptozotocin and high-fat diet. The results showed that L3 treatment could meliorate dyslipidemia and hyperglycemia, reduce oxidative stress, enhance the activity of antioxidases, increase the nitric oxide level in plasma and aortic arch, decrease the production of reactive oxygen species in pancreas and lectin-like oxidized low-density lipoprotein receptor-1 expression in aortic arch, and meliorate the fatty and atherosclerotic degeneration in aortic arch, thereby preventing the development of diabetes and its complications. These results suggested that L3 can alleviate the diabetic atherosclerosis by multiple effects. This study provided scientific basis for the further research and clinical application of L3.

Topics: Animals; Aorta; Atherosclerosis; Curcumin; Diabetes Mellitus, Experimental; Diet, High-Fat; Hyperglycemia; Hyperlipidemias; Hypoglycemic Agents; Hypolipidemic Agents; Liver; Mice; Nitric Oxide; Nitric Oxide Synthase; Oxidative Stress; Pancreas; Reactive Oxygen Species; Scavenger Receptors, Class E

Curcumin, an antioxidant compound found in Asian spices, was evaluated for its protective effects against ethanol-induced hepatosteatosis, liver injury, antiatherogenic markers, and antioxidant status in rats fed with Lieber-deCarli low menhaden (2.7% of total calories from ω-3 polyunsaturated fatty acids (PUFA)) and Lieber-deCarli high menhaden (13.8% of total calories from ω-3 PUFA) alcohol-liquid (5%) diets supplemented with or without curcumin (150 mg/kg/day) for 8 weeks. Treatment with curcumin protected against high ω-3 PUFA and ethanol-induced hepatosteatosis and increase in liver injury markers, alanine aminotransferase, and aspartate aminotransferase. Curcumin upregulated paraoxonase 1 (PON1) mRNA and caused significant increase in serum PON1 and homocysteine thiolactonase activities as compared to high ω-3 PUFA and ethanol group. Moreover, treatment with curcumin protected against ethanol-induced oxidative stress by increasing the antioxidant glutathione and decreasing the lipid peroxidation adduct 4-hydroxynonenal. These results strongly suggest that chronic ethanol in combination with high ω-3 PUFA exacerbated hepatosteatosis and liver injury and adversely decreases antiatherogenic markers due to increased oxidative stress and depletion of glutathione. Curcumin supplementation significantly prevented these deleterious actions of chronic ethanol and high ω-3 PUFA. Therefore, we conclude that curcumin may have therapeutic potential to protect against chronic alcohol-induced liver injury and atherosclerosis.

Topics: Aldehydes; Animals; Antioxidants; Aryldialkylphosphatase; Atherosclerosis; Biomarkers; Chemical and Drug Induced Liver Injury; Curcumin; Diet; Ethanol; Fatty Acids, Omega-3; Fatty Liver; Female; Glutathione; Lipid Metabolism; Lipid Peroxidation; Oxidative Stress; Rats; Rats, Wistar

Our previous studies have indicated that a novel curcumin derivate nicotinate-curcumin (NC) has beneficial effects on the prevention of atherosclerosis, but the precise mechanisms are not fully understood. Given that autophagy regulates lipid metabolism, the present study was designed to investigate whether NC decreases foam cell formation through restoring autophagy flux in oxidized low-density lipoprotein (ox-LDL)-treated THP-1 cells. Our results showed that ox-LDL (100 μg/ml) was accumulated in THP-1 cells and impaired autophagy flux. Ox-LDL-induced impairment of autophagy was enhanced by treatment with the autophagy inhibitor chloroquine (CQ) and rescued by the autophagy inducer rapamycin. The aggregation of ox-LDL was increased by CQ, but decreased by rapamycin. In addition, colocalization of lipid droplets with LC3-II was remarkably reduced in ox-LDL group. In contrast, NC (10 μM) rescued the impaired autophagy flux by significantly increasing level of LC3-II, the number of autophagolysosomes, and the degradation of p62 in ox-LDL-treated THP-1 cells. Inhibition of the PI3K-Akt-mTOR signaling was required for NC-rescued autophagy flux. Notably, our results showed that NC remarkably promoted the colocalization of lipid droplets with autophagolysosomes, increased efflux of cholesterol, and reduced ox-LDL accumulation in THP-1 cells. However, treatment with 3-methyladenine (3-MA) or CQ reduced the protective effects of NC on lipid accumulation. Collectively, the findings suggest that NC decreases lipid accumulation in THP-1 cells through restoring autophagy flux, and further implicate that NC may be a potential therapeutic reagent to reverse atherosclerosis.

Topics: Adenine; Atherosclerosis; Autophagy; Cell Line; Chloroquine; Cholesterol; Curcumin; Foam Cells; Humans; Lipid Metabolism; Lipoproteins, LDL; Macrophages; Niacin; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Signal Transduction; TOR Serine-Threonine Kinases

To investigated the potential of a novel dendrosomal nanoformulation of curcumin (DNC) in blocking radiation-induced changes in irradiated human umbilical vein endothelial cells (HUVECs), and their adhesion to human THP-1 monocytoid cells.. Co. DNC treatment is a potential preventive method against inflammation and vascular damage from ionizing radiation.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Atherosclerosis; Cell Adhesion; Curcumin; Cytokines; Deoxyguanosine; Glutathione; Human Umbilical Vein Endothelial Cells; Humans; Monocytes; Radiation, Ionizing; Thiobarbituric Acid Reactive Substances

Curcumin possesses significant anti-atherosclerosis properties. Lipocalin-2 (LCN2) is already known as one of the most promising biomarkers of atherosclerosis. However, research on the effect of curcumin on regulating LCN2 expression in atherogenesis is very limited. The aim of the study was to investigate whether curcumin could alleviate atherosclerosis in ApoE-/- mice by down-regulating LCN2 expression.. Fifty apolipoprotein E knockout (ApoE-/-) mice were fed with a western diet for 12 weeks and randomly divided into five groups: model group (Mod), positive control group (Lov, with 30 mg/kg/d lovastatin), three curcumin groups (CurL, CurM and CurH, with 40, 60 and 80 mg/kg/d curcumin), while 10 C57BL/6J mice were fed with a standard mouse chow diet as a control group (Con). LCN2 in serum and aorta, biomarkers of serum lipid and inflammation were determined and the plaque area of the atherosclerosis lesions was quantified.. CurM and CurH group were significantly lower than Mod group in terms of serum LCN2, lipid and inflammatory cytokine levels, plaque area and LCN2 expression in atherosclerotic lesions, similar to lovastatin treatment.. Our findings indicate that dietary curcumin ameliorates western diet-induced atherosclerosis in ApoE-/- mice, which is related to LCN2 down-regulation, anti-hyperlipidemia effect as well as the inhibition of inflammation.

Topics: Animals; Aorta; Apolipoproteins E; Atherosclerosis; Biomarkers; C-Reactive Protein; Cholesterol, HDL; Cholesterol, LDL; Curcumin; Diet, Western; Down-Regulation; Hydrogen-Ion Concentration; Immunohistochemistry; Interleukin-6; Lipocalin-2; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Plaque, Atherosclerotic; Triglycerides; Tumor Necrosis Factor-alpha

Kiom-18 is a novel composition of Cinnamomum cassia, Pinus densiflora, Curcuma longa and Glycyrrhiza glabra. Curcuma longa and Glycyrrhiza glabra, which are traditional medicines in Asia, have been reported to demonstrate preventive effects against atherosclerosis; however, they have not yet been developed into functional atherosclerosis treatments. We therefore studied the anti-atherosclerotic effects and possible molecular mechanisms of Kiom-18 using vascular smooth muscle cells (VSMCs).. To assess the anti-proliferative effect of Kiom-18 in vitro, we performed thymidine incorporation, cell cycle progression, immunoblotting and immunofluorescence assays in VSMCs stimulated by platelet derived-growth factor (PDGF)-BB. In addition, we used LDLr knockout mice to identify the effects of Kiom-18 as a preliminary result in an atherosclerosis animal model.. Kiom-18 inhibited platelet-derived growth factor (PDGF)-BB-stimulated-VSMC proliferation and DNA synthesis. Additionally, Kiom-18 arrested the cell cycle transition of G0/G1 stimulated by PDGF-BB and its cell cycle-related proteins. Correspondingly, the level of p27(kip1) expression was upregulated in the presence of the Kiom-18 extract. Moreover, in an atherosclerosis animal model of LDLr knockout mice, Kiom-18 extract showed a preventive effect for the formation of atherosclerotic plaque and suppressed body weight, fat weight, food treatment efficiency, neutrophil count, and triglyceride level.. These results indicate that Kiom-18 exerts anti-atherosclerotic effects by inhibiting VSMC proliferation via G0/G1 arrest, which upregulates p27(Kip1) expression.

Topics: Animals; Aorta; Atherosclerosis; Cell Proliferation; Cells, Cultured; Cinnamomum aromaticum; Curcuma; Cyclin-Dependent Kinase Inhibitor p27; Cyclin-Dependent Kinase Inhibitor Proteins; Glycyrrhiza; Mice; Mice, Knockout; Pinus; Plant Extracts; Rats; Up-Regulation

Topics: Animals; Antioxidants; Atherosclerosis; Curcumin; Humans; Oxidants

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

A high fat meal, frequently known as western diet (WD), exacerbates atherosclerosis and diabetes. Both these diseases are frequently associated with renal failure. Recent studies have shown that lipopolysaccharide (LPS) leaks into the circulation from the intestine in the setting of renal failure and after WD. However, it is not clear how renal function and associated disorders are affected by LPS. This study demonstrates that circulatory LPS exacerbates renal insufficiency, atherosclerosis and glucose intolerance. Renal insufficiency was induced by 2/3 nephrectomy in LDL receptor knockout mice. Nx animals were given normal diet (Nx) or WD (Nx+WD). The controls were sham operated animals on normal diet (control) and WD (WD). To verify if LPS plays a role in exaggerating renal insufficiency, polymyxin (PM), a known LPS antagonist, and curcumin (CU), a compound known to ameliorate chronic kidney disease (CKD), was given to Nx animals on western diet (Nx+WD+PM and Nx+WD+CU, respectively). Compared to control, all other groups displayed increased circulatory LPS. The Nx+WD cohort had the highest levels of LPS. Nx group had significant renal insufficiency and glucose intolerance but not atherosclerosis. WD had intense atherosclerosis and glucose intolerance but it did not show signs of renal insufficiency. Compared to other groups, Nx+WD had significantly higher cytokine expression, macrophage infiltration in the kidney, renal insufficiency, glucose intolerance and atherosclerosis. PM treatment blunted the expression of cytokines, deterioration of renal function and associated disorders, albeit not to the levels of Nx, and was significantly inferior to CU. PM is a non-absorbable antibiotic with LPS binding properties, hence its beneficial effect can only be due to its effect within the GI tract. We conclude that LPS may not cause renal insufficiency but can exaggerate kidney failure and associated disorders following renal insufficiency.

Topics: Animals; Atherosclerosis; Cholesterol; Curcumin; Diet, High-Fat; Diet, Western; Dietary Fats; Disease Models, Animal; Gene Expression; Glucose Intolerance; Hyperglycemia; Intestinal Mucosa; Intestines; Kidney; Lipopolysaccharides; Macrophages; Mice; Mice, Knockout; Nephrectomy; Polymyxins; Receptors, LDL; Renal Insufficiency

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

A polyherbal formulation consisting of different proportions of Commiphora mukul (Hook ex Stocks) Eng., Salacia reticulata Wight, Terminalia arjuna (Roxb.) Wight & Arn, and Curcuma longa Linn extracts was tested for free-radical scavenging and anti-lipid peroxidative effects on serum and platelets in vitro. The most active formulation (GSTC3) was evaluated for its hypolipidemic potential on a high-fat, high-cholesterol diet (HFD) fed to male Wistar rats for a period of 45 days. At a dose of 100 mg/kg body weight, GSTC3 decreased serum total cholesterol, low-density lipoprotein (LDL), very low-density lipoprotein (VLDL), triglycerides, and phospholipids similar to standard atorvastatin while maintaining high-density lipoprotein (HDL) at normal levels. Significantly lower levels of thiobarbituric acid-reactive substances (TBARS) were observed in both the liver and sera of rats treated with GSTC3. Although the phospholipid levels in liver remained unchanged, lower values of LDL, VLDL, and atherogenic index of plasma as well as higher HMG-CoA/ mevalonate ratios suggested a significant hypolipidemic effect for GSTC3, possibly by partial inhibition of HMG-CoA reductase activity. The histopathological analysis of liver tissue did not reveal lipid accumulation or indicate tissue damage. Overall, the results of this study suggest the hypolipidemic and anti-atherogenic efficacy of a nontoxic herbal formulation.

Topics: Animals; Atherosclerosis; Commiphora; Curcuma; Diet, High-Fat; Dose-Response Relationship, Drug; Free Radical Scavengers; Hypolipidemic Agents; Lipid Peroxidation; Male; Phytotherapy; Plant Extracts; Rats; Rats, Wistar; Salacia; Terminalia

This study was designed to investigate the effect of curcumin on the expression of thrombospondin-4 (THBS-4) in mouse macrophages treated with oxidized low-density lipoprotein (oxLDL). The mouse macrophage cell line ANA-1 was treated with oxLDL. Cell viability was measured by MTT assay. ANA-1 cells were divided into five groups: control group, model group, 5 μM curcumin group, 15 μM curcumin group and 25 μM curcumin group. The gene and protein expression levels of THBS-4 in each group were determined by real-time quantitative polymerase chain reaction (PCR) and western blotting, respectively. MTT assay showed that curcumin concentrations up to 25 μM and oxLDL concentrations up to 20 μg/ml had no significant cytotoxic effects on macrophages at 24 h. Real-time quantitative PCR revealed that THBS-4 mRNA expression was markedly reduced by stimulation with oxLDL, but subsequently significantly increased by treatment with curcumin. Western blotting confirmed that curcumin (5, 15, and 25 μM) significantly prevented the decrease in THBS-4 expression induced by oxLDL (20 μg/ml) in macrophages. Curcumin prevents the decrease in THBS-4 expression induced by oxLDL, which may represent one of the anti-atherosclerotic mechanisms of curcumin.

Topics: Animals; Atherosclerosis; Cell Line; Cell Survival; Curcumin; Down-Regulation; Enzyme Inhibitors; Lipoproteins, LDL; Macrophages; Medicine, Chinese Traditional; Mice; Neovascularization, Physiologic; Thrombospondins

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 male sex has a higher risk to develop coronary artery diseases, including atherosclerosis. The androgen receptor (AR) is expressed in several atherosclerosis-associated cell types, including monocytes/macrophages, endothelial cells (ECs), and smooth muscle cells (SMCs), but its pathophysiological role in each cell type during the development of atherosclerotic lesions remains unclear. Using the Cre-loxP system, we selectively knocked out AR in these 3 cell types and the resultant AR knockout (ARKO) mice, monocyte/macrophage ARKO, EC-ARKO, and SMC-ARKO, were then crossed with the low-density lipoprotein receptor (LDLR) deficient (LDLR(-/-)) mice to develop monocyte/macrophage ARKO-LDLR(-/-), EC-ARKO-LDLR(-/-), and SMC-ARKO-LDLR(-/-) mice for the study of atherosclerosis. The results showed that the monocyte/macrophage ARKO-LDLR(-/-) mice had reduced atherosclerosis compared with the wild-type-LDLR(-/-) control mice. However, no significant difference was detected in EC-ARKO-LDLR(-/-) and SMC-ARKO-LDLR(-/-) mice compared with wild-type-LDLR(-/-) mice, suggesting that the AR in monocytes/macrophages, and not in ECs and SMCs, plays a major role to promote atherosclerosis. Molecular mechanism dissection suggested that AR in monocytes/macrophages upregulated the tumor necrosis factor-α, integrin β2, and lectin-type oxidized LDL receptor 1 molecules that are involved in 3 major inflammation-related processes in atherosclerosis, including monocytes/macrophages migration and adhesion to human umbilical vein ECs, and subsequent foam cell formation. Targeting AR via the AR degradation enhancer, ASC-J9, in wild-type-LDLR(-/-) mice showed similar effects as seen in monocyte/macrophage ARKO-LDLR(-/-) mice with little influence on lipid profile. In conclusion, the AR in monocytes/macrophages plays key roles in atherosclerosis and targeting AR with ASC-J9 may represent a new potential therapeutic approach to battle atherosclerosis.

Topics: Animals; Atherosclerosis; Blotting, Western; CD18 Antigens; Cell Adhesion; Cell Line, Tumor; Cell Movement; Cells, Cultured; Curcumin; Diet, High-Fat; Foam Cells; Human Umbilical Vein Endothelial Cells; Humans; Macrophages; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Models, Biological; Monocytes; Myocytes, Smooth Muscle; Receptors, Androgen; Receptors, LDL; Tumor Necrosis Factor-alpha

Association between circulating lipopolysaccharide (LPS) and metabolic diseases (such as Type 2 Diabetes and atherosclerosis) has shifted the focus from Western diet-induced changes in gut microbiota per se to release of gut bacteria-derived products into circulation as the possible mechanism for the chronic inflammatory state underlying the development of these diseases. Under physiological conditions, an intact intestinal barrier prevents this release of LPS underscoring the importance of examining and modulating the direct effects of Western diet on intestinal barrier function. In the present study we evaluated two strategies, namely selective gut decontamination and supplementation with oral curcumin, to modulate Western-diet (WD) induced changes in intestinal barrier function and subsequent development of glucose intolerance and atherosclerosis. LDLR-/- mice were fed WD for 16 weeks and either received non-absorbable antibiotics (Neomycin and polymyxin) in drinking water for selective gut decontamination or gavaged daily with curcumin. WD significantly increased intestinal permeability as assessed by in vivo translocation of FITC-dextran and plasma LPS levels. Selective gut decontamination and supplementation with curcumin significantly attenuated the WD-induced increase in plasma LPS levels (3.32 vs 1.90 or 1.51 EU/ml, respectively) and improved intestinal barrier function at multiple levels (restoring intestinal alkaline phosphatase activity and expression of tight junction proteins, ZO-1 and Claudin-1). Consequently, both these interventions significantly reduced WD-induced glucose intolerance and atherosclerosis in LDLR-/- mice. Activation of macrophages by low levels of LPS (50 ng/ml) and its exacerbation by fatty acids is likely the mechanism by which release of trace amounts of LPS into circulation due to disruption of intestinal barrier function induces the development of these diseases. These studies not only establish the important role of intestinal barrier function, but also identify oral supplementation with curcumin as a potential therapeutic strategy to improve intestinal barrier function and prevent the development of metabolic diseases.

Topics: Administration, Oral; Animals; Anti-Bacterial Agents; Atherosclerosis; Curcumin; Diet, Western; Intestinal Mucosa; Lipopolysaccharides; Macrophage Activation; Mice; Mice, Knockout; NF-kappa B; Receptors, LDL

Curcumin, the yellow substance found in turmeric, possesses antioxidant, anti-inflammation, anticancer, and lipid-lowering properties. Because we hypothesized that curcumin could ameliorate the development of atherosclerosis, the present study focused on the effects and potential mechanisms of curcumin consumption on high-cholesterol diet-induced atherosclerosis in rabbits. During our study, New Zealand white rabbits were fed 1 of 3 experimental diets: a normal diet, a normal diet enriched with 1% cholesterol (HCD), or an HCD supplemented with 0.2% curcumin. At the end of 8 weeks, blood samples were collected to determine the levels of serum lipids, cytokines, and soluble adhesion molecule levels. Gene expression of adhesion molecules and matrix metalloproteinases (MMPs) in aortas were measured by quantitative real-time polymerase chain reaction and Western blot. Compared with the HCD group, rabbits fed an HCD supplemented with 0.2% curcumin had significantly less aortic lesion areas and neointima thickening. Curcumin reduced the levels of total cholesterol, triglyceride, low-density lipoprotein cholesterol, and oxidized low-density lipoprotein cholesterol in serum by 30.7%, 41.3%, 30.4%, and 66.9% (all P < .05), respectively, but did not affect high-density lipoprotein cholesterol levels. In addition, curcumin attenuated HCD-induced CD36 expression, circulating inflammatory cytokines, and soluble adhesive molecule levels. Curcumin reduced the mRNA and protein expression of intracellular adhesion molecule-1, vascular cell adhesion molecule-1, P-selectin, and monocyte chemotactic protein-1, and it inhibited HCD-induced up-regulation of MMP-1, MMP-2, and MMP-9. Our results demonstrate that curcumin exerts an antiatherosclerotic effect, which is mediated by multiple mechanisms that include lowering serum lipids and oxidized low-density lipoprotein, thus modulating the proinflammatory cytokine levels and altering adhesion molecules and MMP gene expression.

Topics: Animals; Antioxidants; Aorta; Atherosclerosis; CD36 Antigens; Cell Adhesion Molecules; Chemokine CCL2; Cholesterol; Curcuma; Curcumin; Cytokines; Hypercholesterolemia; Intercellular Adhesion Molecule-1; Male; Matrix Metalloproteinases; P-Selectin; Phytotherapy; Plant Extracts; Rabbits; RNA, Messenger; Triglycerides; Up-Regulation; Vascular Cell Adhesion Molecule-1

Artemisiaiwayomogi Kitamura and Curcuma longa Linne. (ACE) has been popularly used to treat atherosclerosis as well as hyperlipidemia in the Asian countries.. Antiatherosclerotic and anti-hyperlipidemic effects of ACE were evaluated at protein and gene expression level by using apoE(-/-) mice.. Apoprotein E deficient (apoE(-/-)) mice were randomly divided into five groups and fed freely Western diet (WD) which contained ACE (50, 100 and 200mg/kg) or curcumin (50mg/kg). The C57/BLJ mice were used as normal and which were fed the WD. After 10 weeks of being fed the WD, the atherosclerosis related mediators and hyperlipidemia induced hepatic steatosis were analyzed in serum, aorta tissue or hepatic tissues.. Ten-week feeding of WD considerably increased the serum lipid profiles including total cholesterol (TC), low density lipoprotein, high density lipoprotein (HDL), triglyceride, TC/HDL ratio and glucose, and also elevated the total reactive oxygen species (ROS) and inflammatory cytokines (tumor necrosis factor-α, TNF-α; and interlukin-6, IL-6) in the serum levels. ACE treatment significantly resolved these alterations. The aortic lesion formation was significantly decreased as were lipid formations by ACE treatment. Moreover, ACE not only caused significant decreases of the lipid drops on the hepatic tissues, but also restored the antioxidant components. The gene expression levels including SREBP-1c, FAS, SCD-1, PPAR-α, CPT-1, IL-6, IL-1β and TNF-α in hepatic tissue were altered by Western diet fed in apoE(-/-) mice, while ACE treatment significantly normalized those alterations.. The ACE treatment is beneficial for atherosclerosis in arterial area and hyperlipidemia induced hepatic tissue steatosis.

Topics: Animals; Apolipoproteins E; Artemisia; Atherosclerosis; Curcuma; Cytokines; Dose-Response Relationship, Drug; Fatty Liver; Gene Expression Regulation; Hyperlipidemias; Lipids; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Plant Extracts; Reactive Oxygen Species

Consumption of repeatedly heated soy oil has been linked with incidence of atherosclerosis particularly in oestrogen deficient states. In the present study, effect of curcumin extract on the prevention of atherosclerosis was evaluated.. Forty eight female Spraque-Dawley rats (weighing 200-250 gm) were divided into eight groups. All groups were fed with 2% cholesterol diet. The sham control groups consisted of vitamin E free-RBD Olein (IV62) that acted as vehicle, and curcumin treated groups without undergoing ovariectomy. The other six groups were subjected to ovariectomy and later treated with vehicle-only, curcumin-only, once heated soy oil (1HSO) with vehicle, 1HSO with curcumin, five times heated soy oil (5HSO) with vehicle and 5HSO with curcumin. Curcumin was administered orally at a dose of 50 mg/kg which was commenced two weeks following ovariectomy. Following four months, the rats were sacrificed and serial sections of arch of aorta were harvested and processed for electron microscopic studies (EM).. EM studies showed thickened tunica intima, fenestration of internal elastic lamina and migration of smooth muscle cells from tunica media to tunica intima in the ovariectomized control, 1HSO and 5HSO treated groups, with the latter being most prominent. There were no significant ultra structural changes in the curcumin-treated groups compared to the non-treated groups.. Oral administration of curcumin at a dose of 50 mg/ kg body weight did not show any changes in the aorta of the ovariectomized rats fed with 2% cholesterol and heated soy oil.

Topics: Animals; Aorta; Atherosclerosis; Curcumin; Diet; Female; Hot Temperature; Microscopy, Electron; Ovariectomy; Rats; Rats, Sprague-Dawley; Soybean Oil

To observe the effect of curcumin on nitric oxide (NO) in plasma of atherosclerotic rabbits, activity of constitutive nitric oxide synthase (cNOS) and asymmetric dimethylarginine (ADMA), and discuss curcumin's effect against AS and its correlation with ADMA.. Thirty-eight male Japanese white rabbits were randomly divided into four groups: the control group (eight rabbits fed with standard diets), the model group (ten rabbits fed with high-fat diets), the low dose curcumin group (ten rabbits fed with high-fat diets and 100 mg . kg-1 d -1 ) and the high dose curcumin group (ten rabbits fed with high-fat diets and 200 mg kg-1 d-1 curcumin). At the end of the 12th week, their plasmas were tested for TC, LDL-C, NO, endothelin (ET) , ADMA and activity of aortic cNOS. Aortic tissues were collected for histological examinations.. The three groups fed with high-fat diets showed higher plasma ADMA and ET than the control group (P <0. 01) , but with decrease in plasma NO concentration and arterial cNOS activity (P <0. 01). Compared with the model group (P <0. 05) , the curcumin groups showed lower plasma ADMA and ET (P <0. 05), but higher plasma NO concentration and arterial cNOS activity than the model group (P <0. 01). There was no significant difference between the two curcumin groups.. Curcumin may play an important protective role in AS process by reducing plasma ADMA level. [Key words] atherosclerosis; asymmetric dimethylarginine; crucumin; nitric oxide; nitric oxide synthase

Topics: Animals; Arginine; Atherosclerosis; Curcumin; Endothelium, Vascular; Male; Nitric Oxide Synthase; Rabbits

Besides joint destruction, extra-articular complications (outside the locomotor system) are frequent in rheumatoid arthritis (RA) patients, especially cardiovascular, hematological and metabolic disorders. Here, we evaluated and compared the protective activity of two different doses of mixture of ginger and turmeric rhizomes powder (1 : 1) suspended in distilled water (GTaq) in alleviating both articular and extra-articular manifestations in rat adjuvant-induced arthritis (AIA).. Arthritis was induced by a single intra-dermal injection of 0.1 mL of Complete Freund's adjuvant (containing heat-killed Mycobacterium tuberculosis) into the palmar surface of the left hind paw after the rats were subjected to light diethyl ether anesthesia. Arthritic rats received orally and daily (for 28 consecutive days) distilled water as vehicle, indomethacin (1.0 mg/kg body weight), or GTaq (200 or 400 mg/kg body weight) from the day of arthritis induction.. The present study showed that GTaq (especially the high dose) was more effective (4.2-38.4% higher, P < 0.05-0.001) than indomethacin (a non-steroidal/anti-inflammatory drug) in alleviating the loss in body weight gain, the histopathological changes observed in ankle joints, blood leukocytosis and thrombocytosis, iron deficiency anemia, serum hypoalbuminemia and globulinemia, the impairment of kidney functions, and the risks for cardiovascular disease in arthritic rats. These protective effects of GTaq were mediated through increasing the food intake and decreasing the systemic inflammation that occur at the appearance of polyarthritis, oxidative stress and dyslipidemia.. Ginger-turmeric rhizomes mixture may be effective against RA severity and complications as shown in an AIA rat model.

Topics: Animals; Anti-Inflammatory Agents; Arthritis, Experimental; Arthritis, Rheumatoid; Atherosclerosis; Biomarkers; Body Weight; Cardiovascular Diseases; Curcuma; Disease Progression; Dyslipidemias; Eating; Freund's Adjuvant; Humans; Indomethacin; Joints; Kidney; Kidney Diseases; Male; Oxidative Stress; Phytotherapy; Plant Preparations; Plants, Medicinal; Rats; Rats, Wistar; Rhizome; Severity of Illness Index; Zingiber officinale

Curcumin, a potent antioxidant extracted from Curcuma longa, confers protection against atherosclerosis, yet the detailed mechanisms are not fully understood. In this study, we examined the effect of curcumin on lipid accumulation and the underlying molecular mechanisms in macrophages and apolipoprotein E-deficient (apoE⁻/⁻) mice.. Treatment with curcumin markedly ameliorated oxidized low-density lipoprotein (oxLDL)-induced cholesterol accumulation in macrophages, which was due to decreased oxLDL uptake and increased cholesterol efflux. In addition, curcumin decreased the protein expression of scavenger receptor class A (SR-A) but increased that of ATP-binding cassette transporter (ABC) A1 and had no effect on the protein expression of CD36, class B receptor type I (SR-BI), or ATP-binding cassette transporter G1 (ABCG1). The downregulation of SR-A by curcumin was via ubiquitin-proteasome-calpain-mediated proteolysis. Furthermore, the curcumin-induced upregulation of ABCA1 was mainly through calmodulin-liver X receptor α (LXRα)-dependent transcriptional regulation. Curcumin administration modulated the expression of SR-A, ABCA1, ABCG1, and SR-BI in aortas and retarded atherosclerosis in apoE⁻/⁻ mice.. Our findings suggest that inhibition of SR-A-mediated oxLDL uptake and promotion of ABCA1-dependent cholesterol efflux are two crucial events in suppression of cholesterol accumulation by curcumin in the transformation of macrophage foam cells.

Topics: Animals; Anticholesteremic Agents; Apolipoprotein A-I; Apolipoproteins E; Atherosclerosis; ATP Binding Cassette Transporter 1; ATP Binding Cassette Transporter, Subfamily G, Member 1; ATP-Binding Cassette Transporters; Calmodulin; Calpain; CD36 Antigens; Cholesterol; Curcumin; Foam Cells; Lipid Metabolism; Lipoproteins; Lipoproteins, LDL; Liver X Receptors; Mice; Mice, Mutant Strains; Orphan Nuclear Receptors; Proteasome Endopeptidase Complex; Scavenger Receptors, Class A; Scavenger Receptors, Class B

The aim of the study was to examine the atheroprotective effect of dietary curcumin in a mouse model of atherosclerosis and to identify its cellular and molecular targets at the vascular level.. ApoE(-/-) mice were fed with curcumin at 0.2% (wt/wt) in diet for 4 months. This supplementation reduced the extent of atherosclerotic lesion by 26% and induced changes in expression of genes implicated in cell adhesion and transendothelial migration or cytoskeleton organization, as revealed by a transcriptomic analysis in the aorta. Expression profile of these genes suggests reduction in both leukocyte adhesion and transendothelial migration. In agreement with this hypothesis, we observed a reduction (-37%) in macrophage infiltration in the plaque, as measured by immunohistochemistry, and, in vitro, a lower adhesion of monocytes to TNF-α-stimulated endothelial cells (-32%) after exposure to a nutritionally achievable concentration of curcumin. These changes in gene expression could be related to the observed increased expression of IκB protein and decrease of TNF-α-induced NF-κB/DNA binding and NF-κB-transcriptional activity upon exposure to curcumin.. Our findings pointed out that the antiatherogenic effect of curcumin could be linked to its effect on gene networks and cell functions related to leukocyte adhesion and transendothelial migration via NF-κB-dependent pathways.

Topics: Animals; Aorta; Apolipoproteins E; Atherosclerosis; Cell Adhesion; Curcumin; Dietary Supplements; Endothelial Cells; Gene Expression Regulation; I-kappa B Proteins; Leukocytes; Macrophages; Mice; Mice, Mutant Strains; Monocytes; NF-kappa B; Protective Agents; Transendothelial and Transepithelial Migration; Tumor Necrosis Factor-alpha

Oxidative stress has been implicated as a causative factor of atherosclerosis. Defense systems against oxidative stress are maintained by radical scavenging antioxidants and/or by regulating the expression of antioxidant genes by activating oxidative stress-sensitive transcription factor: nuclear factor (erythroid-derived 2)-like 2 (Nrf2). We investigated the anti-atherogenic effects of three synthesized compounds (shogaol A: radical scavenging antioxidant activity; shogaol N: Nrf2-activating activity; shogaol N + A: both activities) and curcumin (both activities) in apolipoprotein E (apoE)-deficient mice. We expected compounds with both activities to have additive or synergistic anti-atherogenic effects; however, atherosclerosis was exacerbated significantly by curcumin and slightly by shogaol N + A. Shogaol A, shogaol N, and shogaol N + A showed no significant effect on atherosclerosis development. Immunohistochemical analysis of the aorta revealed that expression of CD36, an Nrf2-regulated gene, was strongly induced by treatment with curcumin. The total antioxidant capacity of plasma collected from mice administered the three compounds was evaluated using a hydrophilic probe, pyranine. Shogaol N or shogaol N + A significantly enhanced the antioxidant capacity of plasma, whereas shogaol A and curcumin did not show this activity. The concentrations of the three shogaol derivatives in plasma were similar (approximately 100 nM), while that of curcumin was much lower. These results suggest that plasma antioxidant capacity is maintained at high levels via Nrf2 activation and that CD36 expression enhances atherosclerosis development.

Topics: Animals; Antioxidants; Aorta; Apolipoproteins E; Atherosclerosis; Caprylates; Catechols; CD36 Antigens; Curcumin; Free Radical Scavengers; Lauric Acids; Macrophages; Male; Mice; NF-E2-Related Factor 2; Oxidative Stress; Up-Regulation

Paraoxonase 1 (PON1) is an enzyme that is mainly synthesised in the liver and protects LDL from oxidation, thereby exhibiting antiatherogenic properties. Using a luciferase reporter gene assay, we tested curcumin for its ability to induce PON1 in Huh7 hepatocytes in culture. Curcumin ( ≥ 10 μmol/l) dose-dependently induced PON1 transactivation in Huh7 cells. However, dietary supplementation of female B6C3F1 mice with curcumin (500 mg/kg diet) for 2 weeks did not increase the hepatic PON1 mRNA and protein levels. No curcumin was detectable in the plasma of the 12 h fasted mice. In conclusion, curcumin may be a potent PON1 inducer in cultured cells in vitro, but not in the liver of curcumin-fed mice because of its low concentrations in vivo.

Topics: Animals; Antioxidants; Aryldialkylphosphatase; Atherosclerosis; Base Sequence; Cell Line; Curcumin; Dietary Supplements; DNA Primers; Enzyme Induction; Female; Hepatocytes; Humans; In Vitro Techniques; Liver; Mice; RNA, Messenger; Transcriptional Activation; Transfection

Two-dimensional difference gel electrophoresis and mass spectrum were used to study the anti-atherosclerosis mechanism of curcumin.. The proteins from RAW264.7 cell and RAW264.7 cell treated with 25 micromol x L(-1) curcumin were labeled with Cy3 or Cy5 randomly. Each Cy3-labeled sample and Cy5-labeled sample was mixed on the same 2-D gel along with a Cy2-labeled mixture of all samples as an internal standard and run on the same gel. The gels were scanned under different wave-length light after electrophoresis. All images were analyzed by DeCyder 6.5 software, and the different proteins were identified by mass spectrum.. The expression of ATP synthesis H+ transporting, MHC class II, non-muscle myosin alkali light chain and cytochrome b5 increased in the RAW264.7 cell treated with 25 micromol x L(-1) curcumin, while the expression of phosphodiesterase 4D, elF-3, Hnrpf protein, vimentin, nucleophosminl and Ranbp 1 decreased.. The anti-atherosclerosis mechanism of curcumin is the result of enhancement of the cell inflammation, antioxidant activity and inhibition of cholesterol transport, reduce of the accumulation of intracellular cholesterol and other factors. In addition, curcumin also had the effect of anti-tumor through regulated tumor cell differentiation and apoptosis.

Topics: Animals; Atherosclerosis; Cell Line; Curcumin; Electrophoresis, Gel, Two-Dimensional; Gene Expression; Major Histocompatibility Complex; Mass Spectrometry; Mice; Proteomics; Reverse Transcriptase Polymerase Chain Reaction

Atherosclerosis is a major cause of cardiovascular disease caused by high cholesterol. Stains are widely prescribed to lower cholesterol levels, but natural dietary compounds may also be effective. Therefore, we studied the effect of the natural dietary compound curcumin on atherosclerosis and its underlying mechanisms based on plasma and hepatic lipid metabolism.. LDLR(-/-) mice were fed a high-cholesterol diet and treated with curcumin, lovastatin or control (n=10 per group) for 18 wk. Aortic arch sections revealed curcumin ameliorated early atherosclerotic lesions, lipid infiltration, ICAM-1 and VCAM-1 localization, similar to lovastatin treatment. Furthermore, curcumin lowered plasma cholesterol, triglycerides, LDL cholesterol and Apo B levels as well as CETP activity, while curcumin increased plasma HDL cholesterol and liver Apo A-I expression, similar to lovastatin treatment. Curcumin caused transcriptional inhibition of HMG-CoA reductase, independent of ACAT1 and ACAT2 expression. Hepatic PPARα and LXRα expression was upregulated by curcumin treatment. Hepatic complement factor D (Cfd) and systemic CRP levels, markers of immune complement pathway activation, were significantly reduced by curcumin treatment.. Long-term curcumin treatment lowers plasma and hepatic cholesterol and suppresses early atherosclerotic lesions comparable to the protective effects of lovastatin. The anti-atherogenic effect of curcumin is mediated via multiple mechanisms including altered lipid, cholesterol and immune gene expression.

Topics: Acetyl-CoA C-Acetyltransferase; Animals; Apolipoprotein A-I; Apolipoproteins B; Atherosclerosis; Cholesterol; Cholesterol, Dietary; Cholesterol, HDL; Cholesterol, LDL; Curcumin; Hydroxymethylglutaryl CoA Reductases; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Intercellular Adhesion Molecule-1; Lipid Metabolism; Lipoproteins; Liver; Liver X Receptors; Lovastatin; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Orphan Nuclear Receptors; PPAR alpha; Triglycerides; Up-Regulation; Vascular Cell Adhesion Molecule-1

Curcuma comosa has been known to have potential use in cardiovascular diseases, but its immunoregulatory role in atherosclerosis development and liver toxicity has not been well studied. We therefore investigated the effects of Curcuma comosa on the expression of atherosclerosis-related cytokine genes in rabbits fed a high-cholesterol diet.. Twelve male New Zealand White rabbits were treated with 1.0% cholesterol for one month and were subsequently treated with 0.5% cholesterol either alone, or in combination with 5mg/kg/day of simvastatin or with 400mg/kg/day of Curcuma comosa powder for three months. The expression of IL-1, MCP-1, TNF-α, IL-10, and TGF-β in the isolated abdominal aorta and liver were determined by real-time RT-PCR. Liver toxicity was determined by hepatic enzyme activity.. Curcuma comosa significantly decreased the expression of pro-inflammatory cytokines, leading to a stronger reduction in IL-1, MCP-1, and TNF-α expression compared to that was suppressed by simvastatin treatment. However, neither Curcuma comosa nor simvastatin affected the expression of anti-inflammation cytokines. In the liver, Curcuma comosa insignificantly decreased the expression of pro-inflammatory cytokines and significantly increased the expression of the anti-inflammatory cytokine IL-10 without altering the activity of hepatic enzymes. In contrast, simvastatin significantly increased the MCP-1 and TNF-α expressions and serum ALT level, without affecting the expression of anti-inflammatory cytokines.. In this study, we demonstrated that Curcuma comosa exerts anti-inflammatory activity in the aorta and liver without causing liver toxicity, indicating that Curcuma comosa is a potential candidate as an alternative agent in cardiovascular disease therapy.

Topics: Animals; Aorta, Abdominal; Atherosclerosis; Base Sequence; Cholesterol, Dietary; Curcuma; Cytokines; DNA Primers; Hypercholesterolemia; Liver; Liver Function Tests; Male; Plants, Medicinal; Rabbits; Reverse Transcriptase Polymerase Chain Reaction

Culinary herbs and spices have been widely used for their hypoglycemic, lipid-lowering, and anti-inflammatory activities. This study examined the physiologic activity of hydrophilic components using extracts of turmeric or laurel leaf powder. Aqueous extracts of turmeric and laurel showed potent inhibitory activity against fructose-mediated glycation with antioxidant ability against low-density lipoprotein (LDL) oxidation and radical scavenging activity. The turmeric and laurel extracts had potent cholesteryl ester transfer protein (CETP) inhibitory ability (up to 23% and 40% inhibition, respectively) at a final concentration of 10 μg/mL. The turmeric and laurel extracts inhibited the cellular uptake of oxidized LDL into macrophages, which is the initial step in atherogenesis. For in vivo testing, zebrafish consumed a high cholesterol diet (HCD) (final concentration, 4% [wt/wt]) with or without turmeric or laurel powder (final concentration, 10% [wt/wt]). The turmeric and laurel groups had a 14% and 12% decrease, respectively, in the weight and height ratios compared to the HCD group. The plasma total cholesterol level was significantly lower in the turmeric and laurel groups (48% and 28% less, respectively, than in the HCD group). Plasma triglycerides were more markedly reduced in the turmeric and laurel groups than in the HCD group (68% and 56% less, respectively, than the HCD group). In conclusion, the hydrophilic extracts of turmeric and laurel potently suppressed the incidence of atherosclerosis via a strong antioxidant potential, prevention of apolipoprotein A-I glycation and LDL phagocytosis, and inhibition of CETP. Consumption of turmeric and laurel extracts exhibited hypolipidemic and antioxidant activities in a hypercholesterolemic zebrafish model.

Topics: Animals; Antioxidants; Apolipoprotein A-I; Atherosclerosis; Biological Transport; Cholesterol Ester Transfer Proteins; Cholesterol, Dietary; Cholesterol, LDL; Curcuma; Disease Models, Animal; Fructose; Hypercholesterolemia; Hypolipidemic Agents; Laurus; Lipid Metabolism; Lipid Peroxidation; Macrophages; Phagocytosis; Phytotherapy; Plant Extracts; Zebrafish

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

To investigate the effects of Zhikepingon the oxyradical andintercellular adhesion molecule-1 (ICAM-1) of experimental early atherosclerosis.. The model of SD rat early atherosclerosis was induced by cholesterol diet. The suspension of Zhikeping and simvastatin were administered intragastrically, respectively. After 10 weeks, the serum lipids, superoxide dismutase (SOD) and maleic dialdehyde (MDA) were detected by automatic biochemistry analyzer. ICAM-1 and its expression of mRNA in aortic wall were detected- by immunohistochemistry and RT-PCR, respectively. Aortic histomorphology was cbserved by HE stainning.. The results showed that the serum lipids, superoxide dismutase (SOD) and maleic dialdehyde (MDA) of treated groups were obviously improved as compared with those of the control group. The tissue pathological damage was improved indifferent degree, and ICAM-1 and its expression of mRNA was decreased obviously.. It is suggested the mechanism of anti-atherosclerosis of Zhikeping have close relationship with the function of its anti-oxidizing and anti-adhesiveness that can protect aortic endothelial cell.

Topics: Animals; Aorta; Atherosclerosis; Curcuma; Curcumin; Intercellular Adhesion Molecule-1; Lipids; Male; Malondialdehyde; Plants, Medicinal; Rats; Rats, Sprague-Dawley; RNA, Messenger; Superoxide Dismutase

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

It is widely appreciated that inflammation and oxidant stress contribute to atherogenesis. Curcumin, a polyphenolic natural compound has been reported to possess anti-inflammatory and anti-oxidant actions. We hypothesized that curcumin could inhibit the development of atherosclerosis in the apoE/LDLR-double knockout mice fed with Western diet (21% fat, 0.15% cholesterol w/w, without cholic acid). Curcumin (purity>or=98%), premixed with diet, was given for 4 months at a dose of 0.3 mg/ per day/ per mouse. In this model curcumin inhibited atherogenesis, measured both by "en face" method (25,15+/-2,9% vs. 19,2+/-0,6%, p<0,05) and "cross-section" method (565867+/-39764 microm2 vs. 299201+/-20373 microm2, p<0,05). Importantly, curcumin influenced neither the concentrations of cholesterol and triglycerides in blood nor animal body weight. To our knowledge, this is the first report that shows the anti-atherogenic effect of low dose of curcumin in fine model of atherosclerosis: gene-targeted apoE/LDLR-double knockout mice.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Aorta; Apolipoproteins E; Atherosclerosis; Curcumin; Diet, Atherogenic; Female; Mice; Mice, Inbred C57BL; Mice, Knockout; Receptors, LDL