curcumin and Diabetes-Mellitus--Type-2

Metabolic diseases have become a serious threat to human health worldwide. It is crucial to look for effective drugs from natural products to treat metabolic diseases. Curcumin, a natural polyphenolic compound, is mainly obtained from the rhizomes of the genus

Topics: Curcumin; Diabetes Mellitus, Type 2; Humans; Metabolic Diseases; Non-alcoholic Fatty Liver Disease; Obesity

The hypoglycemic properties of curcumin supplements in therapeutic doses are well-known and may represent a useful tool for the treatment of chronic diseases such as metabolic syndrome, insulin resistance and type 2 diabetes. The poor bioavailability of curcumin can be improved with the concomitant administration of piperine, with no severe adverse effects on glycemia reported so far in the literature. In this article, we further discuss a previously reported case of a helicopter pilot, affected by grade I obesity who, under curcumin and piperine treatment, experienced a transient loss of consciousness (TLOC), during a low-altitude flight. This episode led to a diagnosis of insulinoma, previously asymptomatic. We hypothesized that the combined effects of curcumin and piperine might have caused a severe hypoglycemic episode and subsequent TLOC. Therefore, further studies should be conducted to evaluate the safety of curcumin and piperine supplementation in subjects with impaired glucose metabolism and insulin secretion.

Topics: Curcumin; Diabetes Mellitus, Type 2; Glucose; Humans; Hypoglycemic Agents; Insulinoma; Pancreatic Neoplasms; Polyunsaturated Alkamides; Unconsciousness

The past couple of decades in particular have seen a rapid increase in the prevalence of type 2 diabetes mellitus (T2DM), a debilitating metabolic disorder characterised by insulin resistance. The insufficient efficacy of current management strategies for insulin resistance calls for additional therapeutic options. The preponderance of evidence suggests potential beneficial effects of curcumin on insulin resistance, while modern science provides a scientific basis for its potential applications against the disease. Curcumin combats insulin resistance by increasing the levels of circulating irisin and adiponectin, activating PPARγ, suppressing Notch1 signalling, and regulating SREBP target genes, among others. In this review, we bring together the diverse areas pertaining to our current understanding of the potential benefits of curcumin on insulin resistance, associated mechanistic insights, and new therapeutic possibilities.

Topics: Adiponectin; Curcumin; Diabetes Mellitus, Type 2; Humans; Insulin; Insulin Resistance; PPAR gamma

Diabetes mellitus has become a global pandemic progressively rising and affecting almost every household in all world regions. Diet is a significant root cause of type II diabetes; thus, the significance of dietary interventions in preventing and managing the disease cannot be neglected. Lowering the glycemic impact of diet is an alternative way of managing type II diabetes while improving insulin sensitivity. Medicinal plants are rich in therapeutic phytochemicals which possess hypoglycemic properties. Therefore, it could be speculated that the glycemic impact of diet can be reduced by adding hypoglycemic plant ingredients without altering the sensory properties of food. The main aim of this review is to discuss dietary interventions to manage diabetes and summarize available information on the hypoglycemic properties of four prime herbs of Asian origin. This article collected, tabulated, and summarized groundbreaking reveals from promising studies. This integrative review provides information on the hypoglycemic properties of ginger, Indian gooseberry, cinnamon, and turmeric and discusses the possibility of those herbs reducing the glycemic impact of a diet once incorporated. Further research should be done regarding the incorporation of these herbs successfully into a regular diet.

Topics: Cinnamomum zeylanicum; Curcuma; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Phyllanthus emblica; Plant Extracts; Zingiber officinale

This study aims to comprehensively review the existing evidence and conduct analysis of updated randomized controlled trials (RCTs) of turmeric (Curcuma longa, CL) and its related bioactive compounds on glycemic and metabolic parameters in patients with type 2 diabetes (T2DM), prediabetes, and metabolic syndrome (MetS) together with a sub-group analysis of different CL preparation forms.. An umbrella review (UR) and updated systematic reviews and meta-analyses (SRMAs) were conducted to evaluate the effects of CL compared with a placebo/standard treatment in adult T2DM, prediabetes, and MetS. The MEDLINE, Embase, The Cochrane Central Register of Control Trials, and Scopus databases were searched from inception to September 2022. The primary efficacy outcomes were hemoglobin A1C (HbA1C) and fasting blood glucose (FBG). The corrected covered area (CCA) was used to assess overlap. Mean differences were pooled across individual RCTs using a random-effects model. Subgroup and sensitivity analyses were performed for various CL preparation forms.. Fourteen SRMAs of 61 individual RCTs were included in the UR. The updated SRMA included 28 studies. The CCA was 11.54%, indicating high overlap across SRMAs. The updated SRMA revealed significant reduction in FBG and HbA1C with CL supplementation, obtaining a mean difference (95% confidence interval [CI]) of -8.129 (-12.175, -4.084) mg/dL and -0.134 (-0.304, -0.037) %, respectively. FBG and HbA1C levels decreased with all CL preparation forms as did other metabolic parameters levels. The results of the sensitivity and subgroup analyses were consistent with those of the main analysis.. CL supplementation can significantly reduce FBG and HbA1C levels and other metabolic parameters in T2DM and mitigate related conditions, including prediabetes and MetS.. PROSPERO (CRD42016042131).

Topics: Adult; Blood Glucose; Curcuma; Diabetes Mellitus, Type 2; Dietary Supplements; Glycated Hemoglobin; Humans; Meta-Analysis as Topic; Metabolic Syndrome; Prediabetic State; Randomized Controlled Trials as Topic; Systematic Reviews as Topic

Cardiovascular diseases (CVDs) contribute to a large part of worldwide mortality. Similarly, two of the major risk factors for these diseases, aging and obesity, are also global problems. Aging, the gradual decline of body functions, is non-modifiable. Obesity, a modifiable risk factor for CVDs, also predisposes to type 2 diabetes mellitus (T2DM). Moreover, it affects not only the vasculature and the heart but also specific fat depots, which themselves have a major impact on the development and progression of CVDs. Common denominators of aging, obesity, and T2DM include oxidative stress, mitochondrial dysfunction, metabolic abnormalities such as altered lipid profiles and glucose metabolism, and inflammation. Several plant substances such as curcumin, the major active compound in turmeric root, have been used for a long time in traditional medicine and for the treatment of CVDs. Newer mechanistic, animal, and human studies provide evidence that curcumin has pleiotropic effects and attenuates numerous parameters which contribute to an increased risk for CVDs in aging as well as in obesity. Thus, curcumin as a nutraceutical could hold promise in the prevention of CVDs, but more standardized clinical trials are required to fully unravel its potential.

Topics: Animals; Cardiovascular Diseases; Curcumin; Diabetes Mellitus, Type 2; Mitochondria; Obesity; Oxidative Stress

Metabolic syndrome (MS) involves people with the following risk factors: obesity, hypertension, high glucose level and hyperlipidemia. It can increase the risk of heart disease, stroke and type 2 diabetes mellitus. The prevalence of MS in the world's adult population is about 20%-25%. Today, there is much care to use medicinal plants. Turmeric (Curcuma longa) as well as curcumin which is derived from the rhizome of the plant, has been shown beneficial effects on different components of MS. Thus, the purpose of this manuscript was to introduce different in vitro, in vivo and human studies regarding the effect of turmeric and its constituent on MS. Moreover, different mechanisms of action by which this plant overcomes MS have been introduced. Based on studies, turmeric and its bioactive component, curcumin, due to their anti-inflammatory and antioxidant properties, have antidiabetic effects through increasing insulin release, antihyperlipidemic effects by increasing fatty acid uptake, anti-obesity effects by decreasing lipogenesis, and antihypertensive effects by increasing nitric oxide. According to several in vivo, in vitro and human studies, it can be concluded that turmeric or curcumin has important values as a complementary therapy in MS. However, more clinical trials should be done to confirm these effects.

Topics: Curcuma; Curcumin; Diabetes Mellitus, Type 2; Humans; Metabolic Syndrome; Plant Extracts; Rhizome

Dysglycemia is a disease state preceding the onset of diabetes and includes impaired fasting glycemia and impaired glucose tolerance. This review aimed to collect and analyze the literature reporting the results of clinical trials evaluating the effects of selected nutraceuticals on glycemia in humans. The results of the analyzed trials, generally, showed the positive effects of the nutraceuticals studied alone or in association with other supplements on fasting plasma glucose and post-prandial plasma glucose as primary outcomes, and their efficacy in improving insulin resistance as a secondary outcome. Some evidences, obtained from clinical trials, suggest a role for some nutraceuticals, and in particular Berberis, Banaba, Curcumin, and Guar gum, in the management of prediabetes and diabetes. However, contradictory results were found on the hypoglycemic effects of Morus, Ilex paraguariensis, Omega-3, Allium cepa, and Trigonella faenum graecum, whereby rigorous long-term clinical trials are needed to confirm these data. More studies are also needed for Eugenia jambolana, as well as for Ascophyllum nodosum and Fucus vesiculosus which glucose-lowering effects were observed when administered in combination, but not alone. Further trials are also needed for quercetin.

Topics: Blood Glucose; Curcumin; Diabetes Mellitus; Diabetes Mellitus, Type 2; Dietary Supplements; Glucose Intolerance; Humans; Hypoglycemic Agents; Prediabetic State; Quercetin

Owing to its prevalent nature, diabetes mellitus has become one of the most serious endocrine illnesses affecting a patient's quality of life due to the manifestation of side effects such as cardiovascular diseases, retinopathy, neuropathy, and nephropathy. Curcumin ((1E, 6E) 21, 7-bis (4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione), a major compound of turmeric, has been used in conventional medicine because of its safe nature and cost-effectiveness to meliorate diabetes and its comorbidities. These effects have also been observed in rodent models of diabetes resulting in a reduction of glycemia and blood lipids. Both the preventive and therapeutic activities of this compound are due to its antioxidant and anti-inflammatory characteristics. Furthermore, preclinical outcomes and clinical investigation demonstrate that the use of curcumin neutralizes insulin resistance, obesity, and hyperglycemia. Despite the many benefits of curcumin, its two limiting factors, solubility and bioavailability, remain a challenge for researchers; therefore, several methods such as drug formulation, nano-drug delivery, and the use of curcumin analogs have been developed to deliver curcumin and increase its bioavailability. PRACTICAL APPLICATIONS: The rise of people with type 2 diabetes has become a major concern at the global healthcare level. The best diabetes treatments today are anti-diabetic drug administration, lifestyle-related interventions (such as healthy eating and daily physical activity), arterial pressure detection, and fat control. The polyphenol curcumin, found in turmeric, can promote health by acting on a variety of cellular signaling pathways. This review article discusses curcumin and its role in the treatment of diabetes.

Topics: Antioxidants; Curcuma; Curcumin; Diabetes Mellitus, Type 2; Health Promotion; Polyphenols; Quality of Life

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

Metabolic diseases are globally popular, and a systematic review and meta-analysis of turmeric and curcuminoids on glucose metabolism among people with metabolic diseases was performed.. We comprehensively searched Web of Science, PubMed, Ovid (including EMBASE and MEDLINE), Scopus, the Cochrane Library and two Chinese databases, Wanfang and CNKI for RCTs that focused on the effects of turmeric and curcuminoids on fasting blood glucose (FBG), hemoglobin A1C (HbA1c), fasting serum insulin (FSI) and HOMA-IR among patients with metabolic diseases. The FBG and HbA1c were the main outcomes to be analyzed. With random-effects models, separate meta-analyses were conducted by inverse-variance and reported as WMD with 95% CIs.. Evidence from 17 RCTs including 22 trials showed that turmeric and curcuminoids lowered FBG by - 7.86 mg/dL (95% CI: -12.04, -3.67 mg/dL; P = 0.0002), HbA1c by - 0.38% (95% CI: -0.52%, -0.23%; P < 0.00001) and HOMA-IR by - 1.01 (95% CI: -1.6, -0.42; P = 0.0008). Moreover, they decreased fasting serum insulin by - 1.69 mU/L (95% CI: -3.22, -0.16 mU/L; P = 0.03) after more than 8 weeks of intervention in a subgroup analysis.. Turmeric and curcuminiods decrease FBG, HbA1c and HOMA-IR significantly among subjects with metabolic disease. Additionally, they may have an effect on FSI concentrations if the intervention period is more than 8 weeks. However, attention should be paid to these outcomes due to the significant heterogeneity.

Topics: Blood Glucose; Curcuma; Diabetes Mellitus, Type 2; Diarylheptanoids; Glycated Hemoglobin; Humans; Insulin; Insulin Resistance; Metabolic Diseases; Randomized Controlled Trials as Topic

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

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Tissue Distribution; Titanium; Toluidines; Tomography, X-Ray Computed; Tooth; Tramadol; Transcription Factor AP-1; Transcription, Genetic; Transfection; Transgender Persons; Translations; Treatment Outcome; Triglycerides; Ubiquinone; Ubiquitin-Specific Proteases; United Kingdom; United States; Up-Regulation; Vascular Stiffness; Veins; Ventricular Remodeling; Viral Load; Virulence Factors; Virus Replication; Vitis; Voice; Voice Quality; Wastewater; Water; Water Pollutants, Chemical; Water-Electrolyte Balance; Weather; Wildfires; Wnt Signaling Pathway; Wound Healing; X-Ray Diffraction; Xenograft Model Antitumor Assays; Young Adult; Zoogloea

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

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

In spite of much awareness, diabetes mellitus continues to remain one of major reasons for mortality and morbidity rate all over the globe. Free radicals cause oxidative stress which is responsible for causing diabetes. The recent advancements in elucidation of ARE/keap1/Nrf2 pathway can help in better understanding of diabetes mellitus. Various clinical trials and animal studies have shown the promising effect of Nrf2 pathway in reversing diabetes by counteracting with the oxidative stress produced. The gene is known to dissociate from Keap1 on coming in contact with such stresses to show preventive and prognosis effect. The Nrf2 gene has been marked as a molecular player in dealing with wide intracellular as well as extracellular cellular interactions in different diseases. The regulation of this gene gives some transcription factor that contain antioxidant response elements (ARE) in their promoter region and thus are responsible for encoding certain proteins involved in regulation of metabolic and detoxifying enzymes.

Topics: Animals; Antioxidant Response Elements; Antioxidants; Clinical Trials as Topic; Curcumin; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Gene Expression Regulation; Humans; Hypoglycemic Agents; Kelch-Like ECH-Associated Protein 1; NF-E2-Related Factor 2; Oxidative Stress; Protein Binding; Reactive Oxygen Species; Signal Transduction

Diabetes mellitus is an important issue for public health, and it is growing in the world. In recent years, there has been a growing research interest on efficacy evidence of the curcumin use in the regulation of glycemia and lipidaemia. The molecular structure of curcumins allows to intercept reactive oxygen species (ROI) that are particularly harmful in chronic inflammation and tumorigenesis models. The aim of our study performed a systematic review and meta-analysis to evaluate the effect of curcumin on glycemic and lipid profile in subjects with uncomplicated type 2 diabetes. The papers included in the meta-analysis were sought in the MEDLINE, EMBASE, Scopus, Clinicaltrials.gov, Web of Science, and Cochrane Library databases as of October 2020. The sizes were pooled across studies in order to obtain an overall effect size. A random effects model was used to account for different sources of variation among studies. Cohen's

Topics: Blood Glucose; Cholesterol, HDL; Cholesterol, LDL; Curcumin; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Humans; Randomized Controlled Trials as Topic; Triglycerides

We conducted a systematic review of human trials examining the effects of dietary phytochemicals on Nrf2 activation. In accordance with the PRISMA guidelines, Medline, Embase and CAB abstracts were searched for articles from inception until March 2020. Studies in adult humans that measured Nrf2 activation (gene or protein expression changes) following ingestion of a phytochemical, either alone or in combination were included. The study was pre-registered on the Prospero database (Registration Number: CRD42020176121). Twenty-nine full-texts were retrieved and reviewed for analysis; of these, eighteen were included in the systematic review. Most of the included participants were healthy, obese or type 2 diabetics. Study quality was assessed using the Cochrane Collaboration Risk of Bias Assessment tool. Twelve different compounds were examined in the included studies: curcumin, resveratrol and sulforaphane were the most common (n = 3 each). Approximately half of the studies reported increases in Nrf2 activation (n = 10); however, many were of poor quality and had an unclear or high risk of bias. There is currently limited evidence that phytochemicals activate Nrf2 in humans. Well controlled human intervention trials are needed to corroborate the findings from in vitro and animal studies.

Topics: Adult; Aged; Antioxidants; Bias; Curcumin; Diabetes Mellitus, Type 2; Humans; Isothiocyanates; Middle Aged; NF-E2-Related Factor 2; Obesity; Oxidative Stress; Phytochemicals; Polyphenols; Resveratrol; Sulfoxides

Free fatty acids (FFAs) and fatty acid synthesis (FAS) activity have significantly contributed to disease states such as insulin resistance, obesity, type 2 diabetes, myocardial infarction, blood pressure, and several types of cancer. Currently, several treatment options are available for patients with these conditions. Due to safety concerns, adverse effects, limited efficacy, and low tolerability associated with many medications, the identification of novel agents with less toxicity and a more favorable outcome is warranted. Curcumin is a phenolic compound derived from the turmeric plant with various biological activities, including anticarcinogenic, antioxidant, antiinflammatory, and hypolipidemic properties. PubMed, Scopus, and Web of Science were searched up to February 2020 for studies that demonstrated the efficacy and mechanisms of curcumin action on FFAs, FAS, and β-oxidation activity, as well as the desaturation system. Most of the evidence is in-vivo and in-vitro studies that demonstrate that curcumin possesses regulatory properties on FFAs levels through its effects on FAS and β-oxidation activity as well as desaturation system, which could improve insulin resistance, obesity, and other FFAs-related disorders. The present study provides a review of the existing in-vitro, in-vivo, and clinical evidence on the effect of curcumin on FFAs and FAS activity, β-oxidation, and desaturation system.

Topics: Curcumin; Diabetes Mellitus, Type 2; Fatty Acids, Nonesterified; Humans; Insulin Resistance; Lipid Metabolism

Amyloidosis is a concept that implicates disorders and complications that are due to abnormal protein accumulation in different cells and tissues. Protein aggregation-associated diseases are classified according to the type of aggregates and deposition sites, such as neurodegenerative disorders and type 2 diabetes mellitus. Polyphenolic phytochemicals such as curcumin and its derivatives have anti-amyloid effects both in vitro and in animal models; however, the underlying mechanisms are not understood. In this review, we summarized possible mechanisms by which curcumin could interfere with self-assembly processes and reduce amyloid aggregation in amyloidosis. Furthermore, we discuss clinical trials in which curcumin is used as a therapeutic agent for the treatment of diseases linking to protein aggregates.

Topics: alpha-Synuclein; Alzheimer Disease; Amyloid beta-Peptides; Amyloidosis; Clinical Trials as Topic; Creutzfeldt-Jakob Syndrome; Curcumin; Diabetes Mellitus, Type 2; Humans; Huntington Disease; Hypoglycemic Agents; Mitochondria; Neuroprotective Agents; Oxidative Stress; Parkinson Disease; Protein Aggregates; tau Proteins

Turmeric, the rhizome of Curcuma longa plant belonging to the ginger family Zingiberaceae, has a history in Ayurvedic and traditional Chinese medicine for treatment of chronic diseases, including metabolic and cardiovascular diseases (CVD). This parallels a prevalence of age- and lifestyle-related diseases, especially CVD and type 2 diabetes (T2D), and associated mortality which has occurred in recent decades. While the chemical composition of turmeric is complex, curcuminoids and essential oils are known as two major groups that display bioactive properties. Curcumin, the most predominant curcuminoid, can modulate several cell signaling pathways involved in the etiology and pathogenesis of CVD, T2D, and related morbidities. Lesser bioactivities have been reported from other curcuminoids and essential oils. This review examines the chemical compositions of turmeric, and related bioactive constituents. A focus was placed on the cellular and molecular mechanisms that underlie the protective effects of turmeric and turmeric-derived compounds against diabetes and CVD, compiled from the findings obtained with cell-based and animal models. Evidence from clinical trials is also presented to identify potential preventative and therapeutic efficacies. Clinical studies with longer intervention durations and specific endpoints for assessing health outcomes are warranted in order to fully evaluate the long-term protective efficacy of turmeric.

Topics: Animals; Cardiovascular Diseases; Curcuma; Curcumin; Diabetes Mellitus, Type 2; Humans; Signal Transduction

Type 2 diabetes mellitus (T2DM) is a chronic metabolic condition, which carries considerable morbidity and mortality. There is growing evidence that curcumin could modulate glucose homeostasis and improve vascular risk in patients with T2DM. The aim of this systematic review was to study the effect of curcumin on glycemic indices in patients with diabetes. A comprehensive search was conducted in PubMed, Scopus, Embase, and Google Scholar up to March 5, 2020, to identify randomized control trials investigating the effect of curcumin supplementation on glycemic indices including fasting blood glucose (FBS), hemoglobin A1c (HbA1C), and the homeostatic model assessment for insulin resistance (HOMA-IR). Eleven articles comprising 1131 individuals with T2DM were included in the study. Treatment with curcumin significantly reduced the level of FBS and HbA1c in 8 and 7 studies, respectively. HOMA-IR was evaluated in five studies, and this was reduced significantly by curcumin supplementation in three of those studies. Patients who took curcumin supplementation over longer periods (≥12 weeks) showed a significant reduction in glycemic indices. The current systematic review showed that curcumin can improve glycemic control in patients with T2DM. However, further studies are required to determine the optimum conditions for these effects of curcumin, particularly regarding readouts of insulin resistance.

Topics: Blood Glucose; Curcumin; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Glycemic Control; Humans; Randomized Controlled Trials as Topic

Type 2 diabetes mellitus (T2DM) is a growing metabolic disease characterized by insulin resistance and hyperglycemia. Current preventative and treatment strategies for T2DM and insulin resistance lack in efficacy resulting in the need for new approaches to prevent and manage/treat the disease better. In recent years, epidemiological studies have suggested that diets rich in fruits and vegetables have beneficial health effects including protection against insulin resistance and T2DM. Curcumin, a polyphenol found in turmeric, and curcuminoids have been reported to have antioxidant, anti-inflammatory, hepatoprotective, nephroprotective, neuroprotective, immunomodulatory and antidiabetic properties. The current review (I of II) summarizes the existing in vitro studies examining the antidiabetic effects of curcumin, while a second (II of II) review summarizes evidence from existing in vivo animal studies and clinical trials focusing on curcumin's antidiabetic properties.

Topics: Animals; Curcuma; Curcumin; Diabetes Mellitus, Type 2; Humans; Hyperglycemia; Hypoglycemic Agents; Insulin Resistance

Type 2 diabetes Mellitus (T2DM) is characterized by chronically increased blood glucose levels, which is associated with impairment of the inflammatory and oxidative state and dyslipidaemia. Although it is considered a world heath concern and one of the most studied diseases, we are still pursuing an effective therapy for both the pathophysiological mechanisms and the complications. Curcumin, a natural compound found in the rhizome of Curcuma longa, is well known for its numerous biological activities, as demonstrated by several studies supporting that curcumin possesses hypoglycaemic, hypolipidemic, anti-inflammatory and antioxidant properties, among others. These effects have been explored to the attenuation of hyperglycaemia and progression of DM complications, being appointed as a potential therapeutic approach. Besides its strong intrinsic activity, the polyphenol has low bioavailability, compromising its therapeutic efficacy. In order to overcome this limitation, several chemical strategies have been applied to curcumin, such as drug delivery systems, chemical manipulation and the use of adjuvant therapies. Given the promising results obtained with curcumin derivative, in this review we discuss not only the therapeutic targets of curcumin, but also its most recently developed analogues and their efficacy in the management of T2DM pathophysiology and complications.

Topics: Animals; Curcumin; Diabetes Complications; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents

Diabetes mellitus is one of the most prevalent chronic diseases in the world; one of its main characteristics is chronic hyperglycemia. Pharmacotherapy and other alternatives such as regular exercise are among the therapeutic methods used to control this pathology and participate in glycemic control, as well as the ingestion of plant extracts with antioxidant effects. Among the different plants used for this purpose, curcumin has potential to be used to attenuate the hyperglycemic condition triggered by diabetes mellitus (DM). Some prior studies suggest that this plant has antioxidant and hypoglycemic potential. This review aims to evaluate the antioxidant and hypoglycemic potential of curcumin supplementation in Type 1 DM (T1DM) and Type 2 DM (T2DM). The search considered articles published between 2010 and 2019 in English and Portuguese, and a theoretical survey of relevant information was conducted in the main databases of scientific publications, including the Virtual Health Library and its indexed databases, PubMed, LILACS (Latin American and Caribbean Literature on Health Sciences-Health Information for Latin America and the Caribbean-BIREME/PAHO/WHO), and Scientific Electronic Library Online (SciELO). The associated use of turmeric and physical exercise has demonstrated antioxidant, anti-inflammatory, and hypoglycemic effects, suggesting that these could be used as potential therapeutic methods to improve the quality of life and survival of diabetic patients.

Topics: Animals; Antioxidants; Blood Glucose; Combined Modality Therapy; Curcuma; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Dietary Supplements; Disease Models, Animal; Exercise Therapy; Humans; Hypoglycemic Agents; Plant Extracts; Quality of Life; Treatment Outcome

Type 2 diabetes mellitus (T2DM) is an ensemble of metabolic diseases that has reached pandemic dimensions all over the world. The multifactorial nature of the pathology makes patient management, which includes lifelong drug therapy and lifestyle modification, extremely challenging. It is well known that T2DM is a preventable disease, therefore lowering the incidence of new T2DM cases could be a key strategy to reduce the global impact of diabetes. Currently, there is growing evidence on the efficacy of the use of medicinal plants supplements for T2DM prevention and management. Among these medicinal plants, curcumin is gaining a growing interest in the scientific community. Curcumin is a bioactive molecule present in the rhizome of the

Topics: Animals; Clinical Trials as Topic; Curcuma; Curcumin; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Phytotherapy; Plant Extracts; Plants, Medicinal

Type 2 diabetes mellitus (T2DM) is a growing metabolic disease characterized by insulin resistance and hyperglycemia. Current preventative and treatment approaches to insulin resistance and T2DM lack in efficacy, resulting in the need for new approaches to prevent and treat the disease. In recent years, epidemiological studies have suggested that diets rich in fruits and vegetables have beneficial health effects, including protection against insulin resistance and T2DM. Curcumin, a polyphenol found in turmeric, and curcuminoids have been reported to have antioxidant, anti-inflammatory, hepatoprotective, nephroprotective, neuroprotective, immunomodulatory and antidiabetic properties. The current review (II of II) summarizes the existing in vivo studies examining the antidiabetic effects of curcumin.

Topics: Animals; Curcumin; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Disease Progression; Female; Humans; Hypoglycemic Agents; Insulin Resistance; Male; Mice; Oxidative Stress; Rats

Clinical evidence suggests that curcuminoids, as a natural polyphenol, can provide support for cardioprotection and glucose metabolism. This meta-analysis assessed the efficacy and safety of curcumin with respect to improving glucose metabolism in patients with cardiovascular risk factors.. Four databases (PubMed, Cochrane Library, Web of Science and Embase) were searched up to June 2018. The inclusion criteria included (i) randomised controlled trials (RCT) and (ii) subjects with risk factors for cardiovascular disease supplemented with curcumin and curcuminoids. A random-effects model and a standardised mean difference with a 95% confidence interval were used to perform quantitative data synthesis. Sensitivity and subgroup analyses were conducted to assess the effects.. Fourteen eligible RCT with 1277 subjects were included. In the overall analyses, curcumin led to significant decreases in fasting blood glucose (FBG), glycated haemoglobin (HbA1c) and homeostatic model assessment of insulin resistance (HOMA-IR). The subgroup analyses suggested that curcumin or combined curcuminoids were more effective at reducing FBG and HbA1c in type 2 diabetes patients than in individuals with metabolic syndrome. Supplementation with curcuminoids at doses ≥300 mg day. Curcumin or combined curcuminoids could exert cardioprotective effects in patients at risk for cardiovascular disease by improving glucose metabolism. However, further high-quality studies and larger sample sizes are required to confirm these results.

Topics: Adult; Aged; Aged, 80 and over; Blood Glucose; Cardiovascular Diseases; Curcumin; Diabetes Mellitus, Type 2; Diarylheptanoids; Dietary Supplements; Female; Glycated Hemoglobin; Humans; Male; Metabolic Syndrome; Middle Aged; Randomized Controlled Trials as Topic

Studies have demonstrated inconsistent effects of curcumin on glycemic outcomes and lipid parameters in patients with prediabetes and type 2 diabetes mellitus (T2DM). This study aimed to assess the effect of curcumin on glycemic control and lipid profile in prediabetes and T2DM.. A systematic search of randomized controlled trials (RCTs) was conducted from inception to June 2018 in electronic sources including AMED, ANZCTR, BioMed Central, CENTRAL, CINAHL, ClinicalTrials.gov, Expanded Academic Index, Google Scholar, ISRCTN, LILACS, MEDLINE, NCCIH, Science Direct, Scopus, Web of Science, and WHO ICTRP. Hand search was also performed. Of the total 486 records, four trials (N = 508) and eight trials (N = 646) were eligible for the meta-analysis of individuals with prediabetes and T2DM, respectively. Curcumin significantly reduced glycosylated hemoglobin (HbA1c) in prediabetics (MD: -0.9%, 95% CI: -1.7 to -0.1%, p = 0.03). Furthermore, T2DM subjects gained favorable reduction in both HbA1c (MD: -0.5%, 95% CI: -1.0 to -0.0%, p = 0.04) and fasting plasma glucose (MD: -11.7 mg/dL, 95% CI: -22.1 to -1.3 mg/dL, p = 0.03). Tendency of lipid profile improvement was also observed.. Our findings may encourage curcumin supplementation based on its meaningful effect on glycemic control and positive trend on lipid outcomes in prediabetes and T2DM.

Topics: Blood Glucose; Cholesterol; Curcumin; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Humans; Lipids; Prediabetic State

Over recent decades, many clinical trials on curcumin supplementation have been conducted on various autoimmune diseases including osteoarthritis, type 2 diabetes, and ulcerative colitis patients. This review attempts to summarize the highlights from these clinical trials. The efficacy of curcumin either alone or in conjunction with existing treatment was evaluated. Sixteen clinical trials have been conducted in osteoarthritis, 14 of which yielded significant improvements in multiple disease parameters. Eight trials have been conducted in type 2 diabetes, all yielding significant improvement in clinical or laboratory outcomes. Three trials were in ulcerative colitis, two of which yielded significant improvement in at least one clinical outcome. Additionally, two clinical trials on rheumatoid arthritis, one clinical trial on lupus nephritis, and two clinical trials on multiple sclerosis resulted in inconclusive results. Longer duration, larger cohort size, and multiple dosage arm trials are warranted to establish the long term benefits of curcumin supplementation. Multiple mechanisms of action of curcumin on these diseases have been researched, including the modulation of the eicosanoid pathway towards a more anti-inflammatory pathway, and the modulation of serum lipid levels towards a favorable profile. Overall, curcumin supplementation emerges as an effective therapeutic agent with minimal-to-no side effects, which can be added in conjunction to current standard of care.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Autoimmune Diseases; Colitis, Ulcerative; Curcumin; Diabetes Mellitus, Type 2; Humans; Lupus Nephritis; Multiple Sclerosis; Osteoarthritis; Randomized Controlled Trials as Topic; Rheumatic Diseases; Treatment Outcome

The growing prevalence of age-related diseases, especially type 2 diabetes mellitus (T2DM) and cancer, has become global health and economic problems. Due to multifactorial nature of both diseases, their pathophysiology is not completely understood so far. Compelling evidence indicates that increased oxidative stress, resulting from an imbalance between production of reactive oxygen species (ROS) and their clearance by antioxidant defense mechanisms, as well as the proinflammatory state contributes to the development and progression of the diseases. Curcumin (CUR; diferuloylmethane), a well-known polyphenol derived from the rhizomes of turmeric

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Curcuma; Curcumin; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Immunomodulation; Neoplasms

　Hemodynamic stresses, including hypertension and myocardial infarction, activate neurohumoral factors such as the sympathetic nervous system and the renin-angiotensin system, and can lead to the progression of heart failure. Established pharmacological agents such as angiotensin II receptor blockers (ARBs), angiotensin-converting enzyme (ACE) inhibitors, and β-blockers target extra-cellular molecules and receptors on the cell membrane. These agents have shown some efficacy for the treatment of heart failure, but the long-term survival rate of patients with heart failure remains low. Additional effective pharmacological approaches are urgently required. Our previous studies have demonstrated that curcumin, a natural polyphenol derived from the root of Curcuma longa, prevented the development of heart failure in rat models of myocardial infarction and hypertensive heart disease. However, until recently curcumin's poor water solubility and extremely low bioavailability have presented serious challenges to its clinical applicability. In recent years, highly absorbable curcumin preparations have been developed using methods such as nanoparticle formation and micellization, and there are now high expectations for their wide clinical application. Our group has developed a highly absorbable curcumin formulation called Theracurmin using nanoparticulation and surface processing techniques. Our preliminary data indicated that Theracurmin may improve left ventricular diastolic function. Furthermore, we have already completed and are currently carrying out several clinical trials using Theracurmin against heart failure-related diseases. This paper summarizes and discusses the potential clinical applications of curcumin, focusing on our highly absorbable curcumin formulation, Theracurmin.

Topics: Administration, Oral; Animals; Biological Availability; Curcumin; Diabetes Mellitus, Type 2; Disease Models, Animal; Drug Compounding; Heart Failure; Humans; Life Style; Nanoparticles; Nanotechnology; Phytotherapy; Pulmonary Disease, Chronic Obstructive; Rats; Solubility

Curcumin, the bioactive component of turmeric, has been used for the treatment of several diseases including diabetes and its complications. Curcumin has been shown to exert pleiotropic effects by modulating different signaling molecules, including transcription factors, chemokines, cytokines, and adipokines. Disturbed regulation of adipokines, which include adiponectin, leptin, resistin, and visfatin, are implicated in the development of insulin resistance and Type 2 diabetes. Here, we review the findings of in vitro, in vivo, and clinical studies on the modulating effects that curcumin treatment exerts on adipokines. Additionally, we examine the potential beneficial effects of the activity of curcumin in the prevention and treatment of diabetes and its comorbidities. J. Cell. Biochem. 118: 4170-4182, 2017. © 2017 Wiley Periodicals, Inc.

Topics: Adipokines; Animals; Curcumin; Cytokines; Diabetes Complications; Diabetes Mellitus, Type 2; Female; Humans; Insulin Resistance; Male

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

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

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

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

Fibrillar aggregates of human islet amyloid polypeptide, hIAPP, a pathological feature seen in some diabetes patients, are a likely causative agent for pancreatic beta-cell toxicity, leading to a transition from a state of insulin resistance to type II diabetes through the loss of insulin producing beta-cells by hIAPP induced toxicity. Because of the probable link between hIAPP and the development of type II diabetes, there has been strong interest in developing reagents to study the aggregation of hIAPP and possible therapeutics to block its toxic effects. Natural products are a class of compounds with interesting pharmacological properties against amyloids which have made them interesting targets to study hIAPP. Specifically, the ability of polyphenolic natural products, EGCG, curcumin, and resveratrol, to modulate the aggregation of hIAPP is discussed. Furthermore, we have outlined possible mechanistic discoveries of the interaction of these small molecules with the peptide and how they may mitigate toxicity associated with peptide aggregation. These abundantly found agents have been long used to combat diseases for many years and may serve as useful templates toward developing therapeutics against hIAPP aggregation and toxicity.

Topics: Catechin; Curcumin; Diabetes Mellitus, Type 2; Humans; Insulin-Secreting Cells; Islet Amyloid Polypeptide; Resveratrol; Stilbenes

Curcumin ((1E,6E)-1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione), the main component of the Indian spice turmeric, has been used in traditional medicine to improve diabetes and its comorbidities. Since the last two decades, scientific research has shown that in addition to its antioxidant properties, curcumin could also work as protein homeostasis regulator and it is able to modulate other intracellular pathways. Curcumin supplementation has been proposed to improve insulin resistance (IR) through the activation of the insulin receptor and its downstream pathways in several experimental models, pointing out that its clinical use may be a good and innocuous strategy to improve IR-related diseases. IR is associated with many diseases and syndromes like carbohydrate intolerance, diabetes, metabolic syndrome, and cardiovascular disease. Therefore, it is imperative to identify safe therapeutic interventions aimed to reduce side effects that could lead the patient to leave the treatment. To date, many clinical trials have been carried out using turmeric and curcumin to improve metabolic syndrome, carbohydrate intolerance, diabetes, and obesity in individuals with IR. Results so far are inconclusive because dose, time of treatment, and type of curcumin can change the study outcome significantly. However, there is some clinical evidence suggesting a beneficial effect of curcumin on IR. In this review, we discuss the factors that could influence curcumin effects in clinical trials aimed to improve IR and related diseases, and the conclusions that can be drawn from results obtained so far. © 2016 BioFactors, 42(6):561-580, 2016.

Topics: Animals; Antioxidants; Clinical Trials as Topic; Curcumin; Diabetes Mellitus, Type 2; Humans; Insulin Resistance; Molecular Targeted Therapy; Obesity; Oxidative Stress; Receptor, Insulin

Polyphenols are members of a very large family of plant-derived compounds that may have beneficial effects on human health, and thus their study has become an increasingly important area of human nutrition research. Considering that it is increasingly accepted that chronic sub-acute inflammation plays an important role in the development of insulin resistance and of diabetes in animals and in humans, the aim of the present review is to compile information concerning the anti-inflammatory effects of non-flavonoid polyphenols on diabetes prevention and/or treatment. Most of these studies have been carried out with different cultured cells and using animal models displaying different types of diabetes, such as diabetes induced by streptozotocin or streptozotocin-nicotinamide, genetic diabetes or diabetes induced by high-fat feeding. In general terms, non-flavonoid polyphenols reduce the production of inflammatory mediators, such as IL-1β, IL-8, MCP-1, COX-2 or iNOS in these animal models of diabetes. This effect is accompanied in the vast majority of these studies by improved insulin action. In addition, some of the non-flavonoid polyphenols are also able to ameliorate or prevent several pathological alterations associated with the development of diabetes, such as nephropathy, cardiopathy or retinopathy. Very little information has been reported with regard to human studies to date. Thus, new studies are needed to confirm if the beneficial effects observed in preclinical studies can apply to human beings.

Topics: Animals; Anti-Inflammatory Agents; Clinical Trials as Topic; Curcumin; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Disease Models, Animal; Humans; Hydroxybenzoates; Phenols; Polyunsaturated Alkamides; Stilbenes

Nonalcoholic steatohepatitis (NASH) is the advanced form of nonalcoholic fatty liver disease, which is often accompanied by obese and/or type II diabetes mellitus. Approximately one-third of NASH patients develop hepatic fibrosis. Hepatic stellate cells are the major effector cells during liver fibrogenesis. Advanced liver fibrosis usually proceeds to cirrhosis and even hepatocellular carcinoma, leading to liver failure, portal hypertension and even death. Currently, there are no approved agents for treatment and prevention of liver fibrosis in human beings. Curcumin, the principal curcuminoid of turmeric, has been reported to show antitumor, antioxidant, and anti-inflammatory properties both in in vitro and in vivo systems. Accumulating data shows that curcumin plays a critical role in combating liver fibrogenesis. This review will discuss the inhibitory roles of curcumin and update the underlying mechanisms by which curcumin targets in inhibiting hepatic stellate cell activation.

Topics: Animals; Curcumin; Diabetes Mellitus, Type 2; Disease Models, Animal; Hepatic Stellate Cells; Humans; In Vitro Techniques; Leptin; Lipid Metabolism; Liver Cirrhosis; Oxidative Stress; Signal Transduction

There is a pressing need for countermeasures against diabetes, which has increased in incidence, becoming a global issue. Glucagon-like peptide-1 (GLP-1), a molecule secreted in enteroendocrine L cells in the lower small and large intestines, is thought to be one of the most important molecular targets for the prevention and treatment of diabetes. There has been increasing interest in the possible ability of dietary factors to treat diabetes via modulating GLP-1 secretion. There is thought to be a close relationship between incretin and diet, and the purported best approach for using dietary factors to increase GLP-1 activity is promotion of secretion of endogenous GLP-1. It have been reported that nutrients as well as various non-nutrient dietary factors can function as GLP-1 secretogogues. Here, we present our findings on the GLP-1 secretion-stimulating functions of two dietary factors, curcumin and extract of edible sweet potato leaves, which contain caffeoylquinic acid derivatives. However, it is necessary to reveal in greater detail the stimulation of GLP-1 secretion by dietary factors for preventing and treating diabetes. It is desirable to clarify the exact GLP-1 secretory pathway, the effect of metabolites derived from dietary factors in gut lumen, and the relationship between incretin and meal.

Topics: Amino Acids; Curcumin; Diabetes Mellitus, Type 2; Diet; Dietary Supplements; Glucagon-Like Peptide 1; Humans; Ipomoea batatas; Lipid Metabolism; Molecular Targeted Therapy

Curcumin is the yellow-colored bioactive constituent of the perennial plant, Curcuma longa L., which possesses a wide range of physiological and pharmacological properties such as antioxidant, anti-inflammatory, anticancer, neuroprotective and anti-diabetic activities. Anti-diabetic activity of curcumin may be due to its potent ability to suppress oxidative stress and inflammation. Moreover, it shows a beneficial role on the diabetesinduced endothelial dysfunction and induces a down-regulation of nuclear factor-kappa B. Curcumin possesses a protective role against advanced glycation as well as collagen crosslinking and through this way, mitigates advanced glycation end products-induced complications of diabetes. Curcumin also reduces blood glucose, and the levels of glycosylated hemoglobin in diabetic rat through the regulation of polyol pathway. It also suppresses increased bone resorption through the inhibition of osteoclastogenesis and expression of the AP-1 transcription factors, c-fos and c-jun, in diabetic animals. Overall, scientific literature shows that curcumin possesses anti-diabetic effects and mitigates diabetes complications. Here we report a systematical discussion on the beneficial role of curcumin on diabetes and its complications with emphasis on its molecular mechanisms of actions.

Topics: Biological Availability; Curcumin; Diabetes Complications; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Molecular Structure

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

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

Diet has been recognized as a corner stone in the management of diabetes mellitus. Spices are the common dietary adjuncts that contribute to the taste and flavour of foods. Besides, spices are also known to exert several beneficial physiological effects including the antidiabetic influence. This review considers all the available information from animal experimentation as well as clinical trials where spices, their extracts or their active principles were examined for treatment of diabetes. Among the spices, fenugreek seeds (Trigonella foenumgraecum), garlic (Allium sativum), onion (Allium cepa), and turmeric (Curcuma longa) have been experimentally documented to possess antidiabetic potential. In a limited number of studies, cumin seeds (Cuminum cyminum), ginger (Zingiber officinale), mustard (Brassica nigra), curry leaves (Murraya koenigii) and coriander (Coriandrum sativum) have been reported to be hypoglycaemic.

Topics: Allium; Animals; Coriandrum; Cuminum; Curcuma; Diabetes Mellitus; Diabetes Mellitus, Type 2; Food Additives; Humans; Murraya; Spices; Trigonella; Zingiber officinale

Type 2 diabetes has become a global epidemic. Modern medicines, despite offering a variety of effective treatment options, can have several adverse effects. Ayurveda, a science that uses herbal medicines extensively, originated in India. Of considerable interest is the adoption of Ayurveda by the mainstream medical system in some European countries (e.g., Hungary), emphasizing this modality is increasing worldwide recognition. From ancient times, some of these herbal preparations have been used in the treatment of diabetes. This paper reviews the accumulated literature for 10 Indian herbs that have antidiabetic activity and that have been scientifically tested. Few of these herbs, such as Momordica charantia, Pterocarpus marsupium, and Trigonella foenum greacum, have been reported to be beneficial for treating type 2 diabetes. Mechanisms such as the stimulating or regenerating effect on beta cells or extrapancreatic effects are proposed for the hypoglycemic action of these herbs.

Topics: Aegle; Cucumis; Cucurbitaceae; Curcuma; Diabetes Mellitus, Type 2; Glycerides; Gymnema; Humans; Lythraceae; Medicine, Ayurvedic; Phytotherapy; Plant Extracts; Plants, Medicinal; Pterocarpus; Risk Factors; Terpenes; Tinospora; Trigonella

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

Metabolic syndrome (MetS) as a cluster of conditions including hyperlipidemia, hypertension, hyperglycemia, insulin resistance, and abdominal obesity is linked to cardiovascular diseases and type 2 diabetes. Evidence suggested that intake of curcumin and coenzyme Q10 may have therapeutic effects in the management of MetS.. We investigated the effects of curcumin and/or coenzyme Q10 supplementation on metabolic syndrome components including systolic blood pressure (SBP), diastolic blood pressure (DBP), waist circumference (WC), triglyceride (TG), high density lipoprotein-cholesterol (HDL-c) and fasting plasma glucose (FPG) as primary outcomes, and total cholesterol (TC), low density lipoprotein-cholesterol (LDL-c) and body mass index (BMI) as secondary outcomes in subjects with MetS.. In this 2 × 2 factorial, randomized, double-blinded, placebo-controlled study, 88 subjects with MetS were randomly assigned into four groups including curcumin plus placebo (CP), or coenzyme Q10 plus placebo (QP), or curcumin plus coenzyme Q10 (CQ), or double placebo (DP) for 12 weeks.. The CP group compared with the three other groups showed a significant reduction in HDL-c (P = 0.001), TG (P <  0.001), TC (P <  0.001), and LDL-c (P <  0.001). No significant differences were seen between the four groups in terms of SBP, DBP, FPG, WC, BMI and weight.. Curcumin improved dyslipidemia, but had no effect on body composition, hypertension and glycemic control. Furthermore, coenzyme Q10 as well as the combination of curcumin and coenzyme Q10 showed no therapeutic effects in subjects with MetS. The trial was registered on 09/21/2018 at the Iranian clinical trials website (IRCT20180201038585N2), URL: https://www.irct.ir/trial/32518 .

Topics: Blood Glucose; Cholesterol, HDL; Cholesterol, LDL; Curcumin; Diabetes Mellitus, Type 2; Dietary Supplements; Humans; Hypertension; Iran; Metabolic Syndrome; Triglycerides; Ubiquinone

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

Topics: 3T3-L1 Cells; A Kinase Anchor Proteins; Acetates; Achilles Tendon; Acute Kidney Injury; Acute Pain; Acyclic Monoterpenes; Adenine Nucleotides; Adhesins, Escherichia coli; Adipocytes; Adipocytes, Brown; Adipogenesis; Administration, Inhalation; Administration, Oral; Adrenal Cortex Hormones; Adsorption; Adult; Aeromonas hydrophila; Africa; Aged; Aged, 80 and over; Agrobacterium tumefaciens; Air; Air Pollutants; Air Pollution; Air Pollution, Indoor; Algorithms; Alkaloids; Alkynes; Allosteric Regulation; Amines; Amino Acid Sequence; Amino Acids; Amino Acids, Branched-Chain; Aminoisobutyric Acids; Aminopyridines; Amyotrophic Lateral Sclerosis; Anaerobic Threshold; Angiography; Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Animal Distribution; Animal Feed; Animal Nutritional Physiological Phenomena; Animals; Ankle Joint; Anti-Bacterial Agents; Anti-HIV Agents; Anti-Inflammatory Agents; Antibodies, Bacterial; Antifungal Agents; Antimalarials; Antineoplastic Agents; Antineoplastic Agents, Phytogenic; Antioxidants; Antiretroviral Therapy, Highly Active; Antiviral Agents; Aotidae; Apelin; Apoptosis; Arabidopsis Proteins; Argentina; Arginine; Artemisinins; Arthritis, Experimental; Arthritis, Rheumatoid; Arthroscopy; Aspergillus; Aspergillus niger; Asteraceae; Asthma; ATP Binding Cassette Transporter, Subfamily B, Member 1; ATP Binding Cassette Transporter, Subfamily G, Member 2; Auditory Cortex; Autoantibodies; Autophagy; Bacteria; Bacterial Infections; Bacterial Proteins; Bacterial Typing Techniques; Base Composition; Base Sequence; Basketball; Beclin-1; Benzhydryl Compounds; Benzimidazoles; Benzo(a)pyrene; Benzofurans; Benzoxazines; Bereavement; beta Catenin; beta-Lactamase Inhibitors; beta-Lactamases; beta-Lactams; Betacoronavirus; Betaine; Binding Sites; Biofilms; Biological Assay; Biological Availability; Biological Evolution; Biomarkers; Biomechanical Phenomena; Biopolymers; Biopsy; Bismuth; Blood Glucose; Blood Platelets; Blood Pressure; Body Composition; Body Weight; Bone Marrow; Bone Marrow Cells; Bone Regeneration; Boron; Botrytis; Brain Ischemia; Brain Neoplasms; Brain-Derived Neurotrophic Factor; Brazil; Breast Neoplasms; Breath Tests; Bronchoalveolar Lavage Fluid; Burkholderia; C-Reactive Protein; Caenorhabditis elegans; Caenorhabditis elegans Proteins; Calcification, Physiologic; Calcium; Calcium Signaling; Calorimetry, Differential Scanning; Cameroon; Camptothecin; Candida; Candida albicans; Capillaries; Carbapenem-Resistant Enterobacteriaceae; Carbapenems; Carbohydrate Conformation; Carbon; Carbon Dioxide; Carbon Isotopes; Carcinoma, Ovarian Epithelial; Cardiac Output; Cardiomyopathy, Hypertrophic; Cardiotonic Agents; Cardiovascular Diseases; Caregivers; Carps; Case-Control Studies; Catalase; Catalysis; Cats; CD4 Lymphocyte Count; Cell Culture Techniques; Cell Differentiation; Cell Line, Tumor; Cell Membrane; Cell Movement; Cell Proliferation; Cell Survival; Cells, Cultured; Cellulose; Centrosome; Ceratopogonidae; Chickens; Child; China; Cholera Toxin; Choline; Cholinesterases; Chromatography, High Pressure Liquid; Chromatography, Liquid; Chromatography, Micellar Electrokinetic Capillary; Chromatography, Reverse-Phase; Chronic Disease; Cinnamates; Cities; Citrates; Climate Change; Clinical Trials, Phase III as Topic; Coal; Coal Mining; Cohort Studies; Coinfection; Colchicine; Colony Count, Microbial; Colorectal Neoplasms; Coloring Agents; Common Cold; Complement Factor H; Computational Biology; Computer Simulation; Continuous Positive Airway Pressure; Contrast Media; Coordination Complexes; Coronary Artery Bypass; Coronavirus 3C Proteases; Coronavirus Infections; Coronavirus Protease Inhibitors; Corynebacterium glutamicum; Cosmetics; COVID-19; Creatinine; Cross-Sectional Studies; Crotonates; Crystallography, X-Ray; Cues; Culicidae; Culture Media; Curcuma; Cyclopentanes; Cyclopropanes; Cymbopogon; Cystine; Cytochrome P-450 CYP2B6; Cytochrome P-450 CYP2C19; Cytochrome P-450 CYP2C19 Inhibitors; Cytokines; Databases, Genetic; Death; Dendritic Cells; Density Functional Theory; Depsides; Diabetes Mellitus, Type 2; Diamond; Diarylheptanoids; Dibenzofurans; Dibenzofurans, Polychlorinated; Diclofenac; Diet; Dietary Carbohydrates; Dietary Supplements; Diffusion Magnetic Resonance Imaging; Dioxins; Diphenylamine; Disease Outbreaks; Disease Susceptibility; Disulfides; Dithiothreitol; Dizocilpine Maleate; DNA Methylation; DNA-Binding Proteins; DNA, Bacterial; Dogs; Dose-Response Relationship, Drug; Double-Blind Method; Doublecortin Protein; Drosophila melanogaster; Droughts; Drug Carriers; Drug Combinations; Drug Delivery Systems; Drug Liberation; Drug Resistance; Drug Resistance, Bacterial; Drug Resistance, Neoplasm; Drug Screening Assays, Antitumor; Dust; Dynactin Complex; Dysferlin; Echo-Planar Imaging; Echocardiography; Edaravone; Egypt; Elasticity; Electrodes; Electrolytes; Emodin; Emtricitabine; Endometriosis; Endothelium, Vascular; Endotoxins; Energy Metabolism; Energy Transfer; 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Non-alcoholic fatty liver disease (NAFLD) is a global health problem with increasing prevalence among overweight and obese patients. It is strongly associated with conditions of insulin resistance including type 2 diabetes mellitus (T2DM) and obesity. It has detrimental consequences ranged from simple steatosis to irreversible hepatic fibrosis and cirrhosis. Curcumin is a dietary polyphenol with potential effect in improving NAFLD. Therefore, the aim of this trial was to examine the effect of curcumin supplementation on various aspects of NAFLD. In this trial, a total number of 80 patients were randomised to receive either curcumin at 250 mg daily or placebo for 2 months. Lipid profiles, hepatic enzymes, anthropometric indices and hepatic fat mass were assessed at the baseline and the end of the trial, and compared within the groups. The grade of hepatic steatosis, and serum aspartate aminotransferase (AST) levels were significantly reduced in the curcumin group (p = 0.015 and p = 0.007, respectively) compared to the placebo. There was also a significant reduction in high density lipoprotein (HDL) levels and anthropometric indices in both groups with no significant differences between the two groups. Low dose phospholipid curcumin supplementation each day for 2 months showed significant reduction in hepatic steatosis and enzymes in patients with NAFLD compared to placebo. Further studies of longer duration and higher dosages are needed to assess its effect on other parameters of NAFLD including cardiovascular risk.

Topics: Aspartate Aminotransferases; Curcumin; Diabetes Mellitus, Type 2; Double-Blind Method; Humans; Non-alcoholic Fatty Liver Disease

Management of prediabetes is a critical step to prevent type-2 diabetes. Curcumin and zinc have been studied as an antioxidant, antiinflammatory, and antidiabetic agents. In this clinical trial, 84 subjects were randomized into curcumin (500 mg), zinc (30 mg), zinc and curcumin, and placebo groups for 90 days. At the baseline and the end of the study, the outcomes (fasting plasma glucose (FPG), 2-hour postprandial glucose (2hpp), HbA

Topics: Blood Glucose; Curcumin; Diabetes Mellitus, Type 2; Diet, Reducing; Dietary Supplements; Double-Blind Method; Humans; Insulin; Insulin Resistance; Obesity; Overweight; Prediabetic State; Zinc

Depression in patients with diabetes is associated with poor glycemic control and linked to an increased risk for diabetes complications such as neuropathy. Curcumin has shown potential antidepressant-like activities in some studies. The present study is the first randomized controlled trial to test the efficacy of nano-curcumin supplementation on depression, anxiety, and stress in patients with diabetic polyneuropathy. Eighty patients with diabetes were enrolled in this parallel, double-blind, randomized, placebo-controlled clinical trial. The participants were allocated randomly to the intervention (n = 40) and control (n = 40) groups. They received 80 mg of nano-curcumin or placebo capsules daily for 8 weeks. At baseline and end of study, anthropometric measurements, dietary intake, physical activity, glycemic indices, and severity of neuropathy were assessed. The depression, anxiety, and stress level were measured by Depression, Anxiety, Stress Scale (DASS-21-items) questionnaire before and after the intervention. After intervention, there was a significant reduction in the mean score of depression in the nano-curcumin group (from 16.7 [3.1] to 15.3 [2.6]) compared with placebo group (17.5 [3.2] to 17.3 [3.1]; p = .02). In addition, a significant fall was found in the mean score of anxiety in the nano-curcumin group (from 22.4 [4.03] to 20.6 [3.4]) compared with the placebo group (21.9 [3.5] to 21.2 [3.5]; p = .009). Changes in stress score were not statistically significant between the two groups. These findings suggested that nano-curcumin supplementation for 8 weeks was effective in reducing depression and anxiety scores in patients with diabetic polyneuropathy.

Topics: Adult; Antidepressive Agents; Anxiety; Curcumin; Depression; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Dietary Supplements; Double-Blind Method; Female; Humans; Iran; Male; Middle Aged; Nanoparticles; Placebos; Stress, Psychological; Surveys and Questionnaires

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

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

The prevalence of prediabetes is increasing worldwide. Unfortunately, prediabetes is related to non-communicable diseases. A high risk of developing type 2 diabetes mellitus (T2DM) is reported in people with prediabetes. Curcumin, a polyphenol, might lead to its therapeutic role in obesity and some obesity-related metabolic diseases. Zinc is a trace element that plays a key role in the synthesis and action of insulin, carbohydrate metabolism, and decreasing inflammation. There has been no clinical trial of zinc and curcumin co-supplementation in patients with prediabetes. In previous studies, the single administration of zinc or curcumin has not been conducted on many of the studied markers in prediabetic patients.. The purpose of this randomized double-blind placebo-controlled clinical trial is to investigate the effect of curcumin and zinc co-supplementation on glycemic measurements, lipid profiles, and inflammatory and antioxidant biomarkers among 84 prediabetic patients with body mass index (BMI) between 25 and 35. Also, liver enzyme, serum zinc, urine zinc, blood pressure, anthropometric parameters, quality of life, adherence to co-supplementation, the side effects of co-supplementation, physical activity, and dietary intake will be assessed. Women or men (18-50 years old for men and 18 years to before menopause for women) will be followed for 3 months (90 days). This study will be conducted at Yazd Diabetes Research Clinic, Shahid Sadoughi University of Medical Sciences.. A diet rich in antioxidants, polyphenols, and phytochemicals has been shown to have a beneficial role in prediabetes. According to the beneficial properties of curcumin or zinc and inadequate evidence, RCTs are needed to assess the effect of curcumin and zinc co-supplementation in native prediabetes patients. We hope the results of the present trial, negative or positive, fill this gap in the literature and facilitate the approach for a much larger, multi-center clinical trial. In conclusion, a synergic effect of co-supplementation along with a weight-loss diet may delay the progression to type 2 diabetes mellitus.. Iranian Registry of Clinical Trials (IRCT) IRCT20190902044671N1 . Registered on 11 October 2019.

Topics: Adolescent; Adult; Antioxidants; Biomarkers; Blood Glucose; Clinical Trials, Phase II as Topic; Curcumin; Diabetes Mellitus, Type 2; Dietary Supplements; Double-Blind Method; Female; Humans; Iran; Lipids; Male; Middle Aged; Obesity; Overweight; Prediabetic State; Quality of Life; Randomized Controlled Trials as Topic; Young Adult; Zinc

Oxidative stress is enhanced by various mechanisms. Serum oxidized low-density lipoprotein (LDL) is a useful prognostic marker in diabetic patients with coronary artery disease. To examine the effects of Theracurmin®, a highly absorbable curcumin preparation, on glucose tolerance, adipocytokines, and oxidized LDL, we conducted a double-blind placebo-controlled parallel group randomized trial in patients with impaired glucose tolerance or non-insulin-dependent diabetes mellitus. We randomly divided the patients with impaired glucose tolerance or non-insulin-dependent diabetes mellitus and stable individuals into the placebo group and the Theracurmin® (180 mg daily for 6 months) group. Of the 33 patients analyzed, 18 (14 males and 4 females) were administered placebo and 15 (9 males and 6 females) were administered Theracurmin®. The patient characteristics did not differ between the two groups. The primary endpoint, HbA1c, did not differ significantly between the two groups. However, the level of

Topics: Adiponectin; Administration, Oral; Adult; Aged; Aged, 80 and over; Antioxidants; Biomarkers; Blood Glucose; Cholesterol, LDL; Curcumin; Diabetes Mellitus, Type 2; Double-Blind Method; Female; Gastrointestinal Absorption; Glucose Intolerance; Glycated Hemoglobin; Humans; Japan; Lipoproteins, LDL; Male; Middle Aged; Time Factors; Treatment Outcome; Young Adult

Lowering insulin resistance and dyslipidaemia may not only enhance glycaemic control but also preserve the β-cell function, reducing the overall risk of developing type 2 diabetes (T2D). The current study was aimed to evaluate the effects of curcumin and/or long-chain omega-3 polyunsaturated fatty acids (LCn-3PUFA) supplementation on glycaemic control and blood lipid levels in individuals at high risk of developing T2D.. This was a 2 × 2 factorial, randomised, double-blinded, placebo-controlled study. Participants were allocated to either double placebo (PL) or curcumin plus placebo matching for LCn-3PUFA (CC), or LCn-3PUFA plus placebo matching for curcumin (FO), or curcumin plus LCn-3PUFA (CC-FO) for twelve weeks. Primary outcome of the trial was glycaemic indices (HbA1C, fasting glucose and insulin). Insulin resistance and sensitivity is measured using homeostatic model assessment model.. A total of sixty-four participants (PL, n = 16; CC, n = 15; FO, n = 17, CC-FO, n = 16) were included in the final analysis. Post-intervention, HbA1c and fasting glucose remained unchanged across all the groups. Insulin sensitivity was significantly improved in the CC supplemented group (32.7 ± 10.3%) compared to PL (P = 0.009). FO and CC-FO tended to improve insulin sensitivity by 14.6 ± 8.5% and 8.8 ± 7.7% respectively, but the difference did not reach significance. Triglyceride levels were further increased in the PL (26.9 ± 7.4%), however, CC and CC-FO supplementation reduced the triglycerides, FO resulted in the greatest reduction in triglycerides (- 16.4 ± 4.5%, P < 0.001).. Reduction in insulin resistance and triglycerides by curcumin and LCn-3PUFA appears to be attractive strategies for lowering the risk of developing T2D. However, this study failed to demonstrate complimentary benefits of curcumin and LCn-3PUFA on glycaemic control.. ACTRN12615000559516 .

Topics: Adult; Aged; Blood Glucose; Curcumin; Diabetes Mellitus, Type 2; Dietary Supplements; Fasting; Fatty Acids, Omega-3; Female; Humans; Insulin; Insulin Resistance; Lipids; Male; Middle Aged; Risk Factors; Triglycerides

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

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

Diabetic Sensorimotor Polyneuropathy (DSPN) is a common complication of diabetes mellitus. Curcumin is the most important ingredient found in turmeric which has a very high potential for eliminating free radicals and inhibiting oxidative stress as an antioxidant agent. The aim of this study was to determine the effect of Nano-curcumin supplementation on the severity of sensorimotor polyneuropathy in patients with Type 2 diabetes mellitus (T2DM).. This parallel, double-blind randomized, placebo-controlled clinical trial was conducted on 80 diabetic patients. Participants were allocated randomly to the intervention (n = 40) and the control group (n = 40). They received 80 mg of nano-curcumin or placebo capsules for 8 weeks. Anthropometric measurements, dietary intake, physical activity, glycemic indices and the severity of DSPN were measured before and after the intervention.. Supplementation of nano curcumin was accounted for a significant reduction in Glycated hemoglobin(HbA1c) (p < 0.001) and Fast Blood Sugar(FBS) (p = 0.004), total score of neuropathy (p < 0.001), total reflex score (p = 0.04) and temperature (p = 0.01) compared to placebo group.. Our findings indicated that curcumin supplementation for 2 months improved and reduced the severity of DSPN in patients with T2DM.

Topics: Adult; Antioxidants; Blood Glucose; Curcuma; Curcumin; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Dietary Supplements; Double-Blind Method; Female; Glycated Hemoglobin; Humans; Male; Middle Aged; Nanoparticles; Oxidative Stress; Polyneuropathies

Residual pockets represent a risk factor for periodontal disease progression. Diabetes Mellitus (DM) may impair prognosis after cause-related therapy, mainly due to the chronic hyperglycemia that negatively influences tissue repair. This study evaluated the clinical efficacy of antimicrobial photodynamic therapy (aPDT) with curcumin (CUR) solution (100 mg/L) and LED irradiation (465-485 nm), as an adjunctive therapy to scaling and root planing (SRP), in the treatment of residual pockets in type 2 diabetic patients.. Individuals with type 2 DM and chronic periodontitis presenting at least one residual pocket per quadrant were selected (n = 25). In each patient, all residual pockets with probing depth (PD) ≥5 mm and bleeding on probing (BOP) were allocated to receive, according to quadrant: 1) SRP (SRP group); 2) SRP and irrigation with CUR solution (100 mg/L) (CUR group); 3) SRP and LED irradiation (InGaN, 465-485 nm, 0.78 cm², 78 mW, 100 mW/cm², 60 s) (LED group); 4) SRP, irrigation with CUR solution (100 mg/L), one minute of pre-irradiation, and LED irradiation (InGaN, 465-485 nm, 60 s) (aPDT group). Clinical parameters of PD, gingival recession (GR), clinical attachment level (CAL), BOP and visible plaque index (PI) were evaluated at baseline, three and six months post-therapies. Differences between the examination periods in each group were analyzed by Friedman's test for non-parametric data, while parametric data were submitted to analysis of variance (One-way ANOVA), followed by Tukey's test. Intergroup comparisons were performed by Kruskal-Wallis test.. In an intergroup comparison, the mean values for PD, GR, CAL, BOP and PI were not different at baseline, three and six months (p > 0.05). The intragroup comparison evidenced reduction in PD and BOP in all treatment groups at three and six months (p < 0.05). Significant CAL gain was notable only for the aPDT and LED groups at three months in comparison to baseline data (p < 0.05).. Treatment of residual pockets in patients with type 2 DM through association of SRP with aPDT (CUR solution 100 mg/L and LED irradiation) or LED irradiation may yield short-term (three months) clinical benefits regarding CAL gain.

Topics: Adult; Aged; Chronic Periodontitis; Combined Modality Therapy; Curcumin; Dental Plaque Index; Dental Scaling; Diabetes Mellitus, Type 2; Female; Humans; Male; Middle Aged; Periodontal Index; Photochemotherapy; Photosensitizing Agents; Root Planing; Single-Blind Method

Diabetes mellitus is the most common metabolic disorder worldwide. This study examined the effect of turmeric supplementation on glycemic status, lipid profile, hs-CRP and total antioxidant capacity in hyperlipidemic type 2 diabetic patients. In this double-blind, randomized clinical trial, 80 hyperlipidemic type 2 diabetic patients were divided into turmeric (2,100 mg powdered rhizome of turmeric daily) and placebo groups for 8 weeks. Body weight, fasting plasma glucose, hemoglobin A1c (HbA1c), serum insulin, triglyceride (TG), total cholesterol, low density lypoprotein cholesterol (LDL-c), high density lypoprotein cholesterol, apolipoprotein A1, apolipoprotein B, high sensitivity C-reactive protein (hs-CRP), and total antioxidant capacity were measured before and after intervention. Statistical analysis was carried out using paired and independent t and chi-square tests. Seventy five patients completed the study. The turmeric group showed significant decreases in body weight, TG, and LDL-c compared with baseline (p value < 0.05). Body mass index, TG, and total cholesterol decreased significantly in the turmeric group compared with the placebo group (p value < 0.05). No significant changes were observed in other parameters between the two groups after intervention (p value < 0.05). Turmeric improved some fractions of lipid profile and decreased body weight in hyperlipidemic patients with type 2 diabetes. It had no significant effect on glycemic status, hs-CRP, and total antioxidant capacity in these patients.

Topics: Adult; Aged; Antioxidants; C-Reactive Protein; Curcuma; Diabetes Mellitus, Type 2; Double-Blind Method; Female; Humans; Hyperlipidemias; Male; Middle Aged

Diabetes mellitus is characterized by increased central arterial stiffness and endothelial dysfunction leading to increased risk of cardiovascular complications. The aim of this study is to evaluate the effect of Curcuma longa on arterial stiffness and endothelial dysfunction in patients with type 2 diabetes mellitus. This randomized controlled trial was conducted in 136 patients of type 2 diabetes. Among them, 114 completed at least one follow-up visit and included for data analysis. Arterial stiffness parameters were measured at baseline and every month for 3 months and endothelial dysfunction markers at baseline and after 3 months of treatment with C. longa or placebo. These parameters were compared between the two groups. Both C. longa and placebo groups were comparable at baseline. After 3 months of treatment, C. longa produced significant reduction from baseline in carotid-femoral pulse wave velocity (p = .002), left brachial-ankle pulse wave velocity (p = .001), aortic augmentation pressure (p = .007), aortic augmentation index (p = .007), and aortic augmentation index at heart rate 75 (p = .018) as compared with the placebo group. Three months treatment with C. longa significantly decreases arterial stiffness as compared with placebo in type 2 diabetes mellitus patients.

Topics: Adult; Ankle Brachial Index; Blood Pressure; Curcuma; Diabetes Mellitus, Type 2; Double-Blind Method; Female; Humans; India; Male; Middle Aged; Plant Extracts; Population Groups; Pulse Wave Analysis; Vascular Stiffness

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

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

The purpose of this open-label study was to investigate the effect of a curcumin-phospholipid lecithin formulation (Meriva®) on visual acuity and optical coherence tomography (OCT) retinal thickness in patients with chronic diabetic macular edema.. Curcumin-phospholipid lecithin formulation (Meriva®, Indena S.p.A, Milan, Italy) was administered as tablets (Norflo®, Eye Pharma, Genoa, Italy) twice a day. Visual acuity and macular edema as measured by OCT before and after curcumin-phospholipid formulation treatment were assessed.. The study included 12 eyes from 11 patients who completed at least a 3-month follow-up period. After 3 months of therapy, no eyes showed reduction in visual acuity, 16% showed stabilization, and 84% showed improvement. The improvement was statistically significant (p = 0.0072). After 3 months of therapy, 92% of eyes showed reduction of macula edema, 8% showed stabilization, and 0% showed an increase (p = 0.009).. Our results, albeit preliminary, suggest that a curcumin-phospholipid formulation (Meriva®), administered as Norflo® tablets, may be feasible in the improvement of visual acuity and reduction of macular edema in patients with diabetic retinopathy.

Topics: Administration, Oral; Aged; Curcumin; Diabetes Mellitus, Type 2; Drug Compounding; Female; Humans; Macular Edema; Male; Middle Aged; Phospholipids; Pilot Projects; Retina; Tomography, Optical Coherence; Visual Acuity

In the current study, we aimed to evaluate the effects of a single dose of curcumin and/or fish oil on postprandial glycaemic parameters in healthy individuals. This was a randomised, placebo-controlled and crossover study. Sixteen (n = 16) volunteers were randomised to receive placebo, curcumin (180 mg) tablets, fish oil (1.2 g long chain omega-3 polyunsaturated fatty acids) capsules and curcumin + fish oil prior to a standard meal on 4 test days separated by a week. Blood glucose, serum insulin and triglycerides were measured at intervals between 0-120 min. Difference between the treatments was measured using two-way repeated measures analysis of variance and pair-wise comparisons using Wilcoxon signed-rank or paired t-test as appropriate. Postprandial glucose concentrations were significantly lower in the curcumin (60.6%, P = 0.0007) and curcumin + fishoil group (51%, P = 0.002) groups at 60 min from baseline. Compared with placebo, area under the curve (AUC) for change in blood glucose concentration was reduced by curcumin (36%, P = 0.003) and curcumin + fishoil (30%, 0.004), but not fish oil alone (p = 0.105). Both curcumin (P = 0.01) and curcumin + fishoil (P = 0.03) treatments significantly lowered postprandial insulin (AUC) by 26% in comparison with placebo. Curcumin, but not fish oil, reduces postprandial glycaemic response and insulin demand for glucose control.

Topics: Adult; Blood Glucose; Cross-Over Studies; Curcumin; Diabetes Mellitus, Type 2; Fatty Acids, Omega-3; Female; Fish Oils; Humans; Hypoglycemic Agents; Insulin; Male; Postprandial Period; Triglycerides

Type 2 diabetes (T2D) is an established risk factor for cardiovascular disease (CVD) and is associated with disturbed metabolism of lipids and lipoproteins. Curcuminoids are natural products with anti-diabetic and lipid-modifying actions but their efficacy in improving dyslipidemia in diabetic individuals has not been sufficiently studied.. To investigate the efficacy of supplementation with curcuminoids, plus piperine as an absorption enhancer, in improving serum lipids in patients with T2D.. In this 12-week randomized double-blind placebo-controlled trial, subjects with T2D (n=118) were assigned to curcuminoids (1000mg/day plus piperine 10mg/day) or placebo plus standard of care for T2D. Serum concentrations of lipids including total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), lipoprotein(a) [Lp(a)], and non-HDL-C were determined at baseline and at the end of trial.. Between-group comparison of change in the study parameters revealed significant reductions in serum levels of TC (-21.86±25.78 versus -17.06±41.51, respectively; p=0.023), non-HDL-C (-23.42±25.13 versus -16.84±41.42, respectively; p=0.014) and Lp(a) (-1.50±1.61 versus -0.34±1.73, respectively; p=0.001) and elevations in serum HDL-C levels (1.56±4.25 versus -0.22±4.62, respectively; p=0.048) in the curcuminoids group as compared with the placebo group (p<0.05). Serum TG and LDL-C changes did not show any significant difference between the study groups (p>0.05).. Curcuminoids supplementation can reduce serum levels of atherogenic lipid indices including non-HDL-C and Lp(a). Therefore, curcuminoids supplementation could contribute to a reduced risk of cardiovascular events in dyslipidemic patients with T2D.

Topics: Adult; Alkaloids; Benzodioxoles; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Curcuma; Curcumin; Diabetes Mellitus, Type 2; Dietary Supplements; Double-Blind Method; Dyslipidemias; Female; Humans; Lipids; Lipoprotein(a); Male; Middle Aged; Phytotherapy; Piperidines; Plant Extracts; Polyunsaturated Alkamides; Triglycerides

Curcumin is a naturally occurring polyphenol derived from tumeric that has been reported to have anti-inflammatory properties with effects on adipokine and ghrelin levels. Adiponectin, leptin and ghrelin modulate energy homeostasis but each has modulatory effects on inflammatory cytokines and the immune system. Therefore, this analysis was performed to investigate the effect of curcumin on adiponectin, leptin and ghrelin.. A double blind randomised control trial comparing curcumin 1000mg with 10mg of piperine daily to placebo over a 12 week period. 118 patients with type 2 diabetes were recruited out of which 50 control and 50 active subjects completed the trial. Adiponectin, leptin, ghrelin and tumor necrosis factor-α (TNF-α) were measured at baseline and 12 weeks.. Between group comparison of the magnitude of changes showed serum levels of leptin (p<0.001), TNF-α (p<0.001) and leptin:adiponectin ratio (p<0.001) to be significantly reduced while serum adiponectin levels were elevated in the curcuminoids versus placebo group (p=0.032). Changes in serum ghrelin levels did not differ between the study groups (p=0.135).. Curcumin supplementation increased adiponectin, whilst the the leptin:adiponectin ratio (a measure of atherosclerosis) and leptin levels were decreased independent of weight change and reflected a decrease in the inflammatory TNF-α levels.

Topics: Adipokines; Adiponectin; Adult; Alkaloids; Anti-Inflammatory Agents, Non-Steroidal; Benzodioxoles; Curcumin; Diabetes Mellitus, Type 2; Double-Blind Method; Drug Therapy, Combination; Female; Ghrelin; Humans; Leptin; Male; Middle Aged; Piperidines; Polyunsaturated Alkamides; Tumor Necrosis Factor-alpha

Lifestyle interventions, including increase in physical activity and dietary counselling, have shown the ability to prevent type 2 diabetes (T2D) in high-risk state individuals, but the prevalence is still skyrocketing in Australia, in line with global prevalence. Currently, no medicines are approved by the Therapeutic Goods Administration in Australia for the management of prediabetes. Therefore, there is a need of developing a safer, biologically efficacious and cost-effective alternative for delaying the transition of individual health state from prediabetes into T2D. In the current trial we propose to evaluate the effects of curcumin and/or long-chain omega-3 polyunsaturated fatty acids on improving glycosylated haemoglobin as a primary outcome, along with secondary outcomes of glycaemic indices, lipid profile and inflammatory parameters.. Eighty individuals diagnosed with prediabetes, aged between 30 and 70 years, will be randomly assigned to double placebo, curcumin alone, fish oil alone or double active groups according to a computer-generated randomisation sequence for 12 weeks. At baseline and post-intervention visits participants will be asked to provide blood samples and undergo body composition measurements. A blood sample is used for estimating glycaemic profiles, lipid profiles and inflammatory parameters (C-reactive protein, whole blood cell count, adiponectin, leptin, interleukin-6). The interim visit includes review on compliance with supplements based on capsule log and capsule count, adverse events and anthropometric measurements. In addition to these procedures, participants provide self-reported questionnaires on dietary intake (using a 3-day food record), a physical activity questionnaire and medical history.. This trial aims to determine whether curcumin and/or long-chain omega-3 polyunsaturated fatty acids affect surrogate markers of glycaemic control which is relevant to delaying T2D. To date 38 participants completed the trial. No changes have been made to the clinical protocol post recruitment. If successful, this trial will provide considerable evidence for performing a larger trial to investigate whether this combination can be administered for preventing or delaying the onset of T2D in high-risk individuals.. ACTRN12615000559516 , registered on 29 May 2015).

Topics: Adult; Aged; Biomarkers; Blood Glucose; Body Composition; Clinical Protocols; Curcumin; Diabetes Mellitus, Type 2; Double-Blind Method; Drug Therapy, Combination; Fatty Acids, Omega-3; Female; Glycated Hemoglobin; Humans; Inflammation Mediators; Lipids; Male; Middle Aged; New South Wales; Prediabetic State; Research Design; Risk Factors; Time Factors; Treatment Outcome

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

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

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

This study aimed to assess the possible beneficial effects of curcumin capsules as lipid-lowering effects and as a permeability glycoprotein (P-gp) inhibitor on the pharmacokinetics and pharmacodynamics of glyburide and as a P-gp substrate with glyburide in patients with type-2 diabetes mellitus. Open-label, randomized control trial was carried out for 11 days on eight type-2 diabetic patients on glyburide therapy. On the first day of the study, following the administration of 5 mg of glyburide, blood samples were collected from the patients at various time intervals ranging from 0.5 to 24 h. Blood sampling was repeated on the 11th day of the study, after treating the patients with curcumin for ten consecutive days. Glyburide concentrations changed at the second hour, Cmax was unchanged, the glucose levels were decreased, Area Under first Movement Curre (AUMC) was increased, and no patient has experienced the hypoglycaemia. The low-density lipoprotein, very-low-density lipoprotein and triglycerides were decreased significantly, and the high-density lipoprotein content increased. The co-administration of curcumin capsules with glyburide may be beneficial to the patients in better glycaemic control. The lipid lowering and antidiabetic properties of the curcumin show as a potential future drug molecule.

Topics: Adult; Blood Glucose; Capsules; Curcumin; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Glyburide; Humans; Hypoglycemic Agents; Lipoproteins, HDL; Lipoproteins, LDL; Triglycerides

Whether supplementation of curcuminoids decreases serum adipocyte-fatty acid binding protein (A-FABP) level and whether this decrease benefits glucose control is unclear. One-hundred participants (n=50 administered curcuminoids, n=50 administered placebo) from our previous report on the effect of curcuminoids on type 2 diabetes in a 3-month intervention were assessed for levels of serum A-FABP, oxidative stress, and inflammatory biomarkers. Curcuminoids supplementation led to significant decreases in serum A-FABP, C-reactive protein (CRP), tumor necrosis factor-α, and interleukin-6 levels. Curcuminoids supplementation also significantly increased serum superoxide dismutase (SOD) activity. The change in serum A-FABP levels showed positive correlations with changes in levels of glucose, free fatty acids (FFAs), and CRP in subjects supplemented with curcuminoids. Further stepwise regression analysis showed that A-FABP was an independent predictor for levels of FFAs, SOD, and CRP. These results suggest that curcuminoids may exert anti-diabetic effects, at least in part, by reductions in serum A-FABP level. A-FABP reduction is associated with improved metabolic parameters in human type 2 diabetes.

Topics: Biomarkers; Blood Glucose; Curcumin; Diabetes Mellitus, Type 2; Fatty Acid-Binding Proteins; Humans; Hypoglycemic Agents; Obesity; Oxidative Stress; Treatment Outcome

We previously found that curcuminoids decreased blood glucose and improved insulin resistance by reducing serum free fatty acids (FFAs) and increasing fatty acid oxidation in skeletal muscle of diabetic rats. This study was to investigate whether curcuminoids have beneficial effects on type 2 diabetic patients, and its possible mechanisms.. Overweight/obese type 2 diabetic patients (BMI ≥ 24.0; fasting blood glucose ≥ 7.0 mmol/L or postprandial blood glucose ≥11.1 mmol/L) were randomly assigned to curcuminoids (300 mg/day) or placebo for 3 months. Bodyweight, glycosylated hemoglobin A1c (HbA1c ,% ), serum fasting glucose, FFAs, lipids, and lipoprotein lipase (LPL) were determined. A total of 100 patients (curcuminoids, n = 50; placebo, n = 50) completed the trial. Curcuminoids supplementation significantly decreased fasting blood glucose (p < 0.01), HbA1c (p = 0.031), and insulin resistance index (HOMA-IR) (p < 0.01) in type 2 diabetic patients. Curcuminoids also led to a significant decrease in serum total FFAs (p < 0.01), triglycerides (P = 0.018), an increase in LPL activity (p < 0.01).. These findings suggest a glucose-lowering effect of curcuminoids in type 2 diabetes, which is partially due to decrease in serum FFAs, which may result from promoting fatty acid oxidation and utilization.

Topics: Adolescent; Adult; Aged; Blood Glucose; Body Weight; Curcumin; Diabetes Mellitus, Type 2; Double-Blind Method; Fatty Acids, Nonesterified; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Insulin Resistance; Lipoprotein Lipase; Male; Middle Aged; Obesity; Postprandial Period; Triglycerides; Young Adult

To assess the efficacy of curcumin in delaying development of type 2 diabetes mellitus (T2DM) in the prediabetic population.. This randomized, double-blinded, placebo- controlled trial included subjects (n = 240) with criteria of prediabetes. All subjects were randomly assigned to receive either curcumin or placebo capsules for 9 months. To assess the T2DM progression after curcumin treatments and to determine the number of subjects progressing to T2DM, changes in β-cell functions (homeostasis model assessment [HOMA]-β, C-peptide, and proinsulin/insulin), insulin resistance (HOMA-IR), anti-inflammatory cytokine (adiponectin), and other parameters were monitored at the baseline and at 3-, 6-, and 9-month visits during the course of intervention.. After 9 months of treatment, 16.4% of subjects in the placebo group were diagnosed with T2DM, whereas none were diagnosed with T2DM in the curcumin-treated group. In addition, the curcumin-treated group showed a better overall function of β-cells, with higher HOMA-β (61.58 vs. 48.72; P < 0.01) and lower C-peptide (1.7 vs. 2.17; P < 0.05). The curcumin-treated group showed a lower level of HOMA-IR (3.22 vs. 4.04; P < 0.001) and higher adiponectin (22.46 vs. 18.45; P < 0.05) when compared with the placebo group.. A 9-month curcumin intervention in a prediabetic population significantly lowered the number of prediabetic individuals who eventually developed T2DM. In addition, the curcumin treatment appeared to improve overall function of β-cells, with very minor adverse effects. Therefore, this study demonstrated that the curcumin intervention in a prediabetic population may be beneficial.

Topics: Curcumin; Diabetes Mellitus, Type 2; Double-Blind Method; Female; Humans; Male; Middle Aged; Plant Extracts; Prediabetic State; Treatment Outcome

End-stage renal disease (ESRD) due to type 2 diabetic nephropathy is a very common condition which is increasing in prevalence, and is associated with high global levels of mortality and morbidity. Both proteinuria and transforming growth factor-β (TGF-β) may contribute to the development of ESRD in patients with diabetic nephropathy. Experimental studies indicate that turmeric improves diabetic nephropathy by suppressing TGF-β. Therefore, this study investigated the effects of turmeric on serum and urinary TGF-β, interleukin-8 (IL-8) and tumour necrosis factor-α (TNF-α), as well as proteinuria, in patients with overt type 2 diabetic nephropathy.. A randomized, double-blind and placebo-controlled study was carried out in the Diabetes Clinic of the Outpatient Department of Shiraz University of Medical Sciences on 40 patients with overt type 2 diabetic nephropathy, randomized into a trial group (n = 20) and a control group (n = 20). Each patient in the trial group received one capsule with each meal containing 500 mg turmeric, of which 22.1 mg was the active ingredient curcumin (three capsules daily) for 2 months. The control group received three capsules identical in colour and size containing starch for the same 2 months.. Serum levels of TGF-β and IL-8 and urinary protein excretion and IL-8 decreased significantly comparing the pre- and post-turmeric supplementation values. No adverse effects related to turmeric supplementation were observed during the trial.. Short-term turmeric supplementation can attenuate proteinuria, TGF-β and IL-8 in patients with overt type 2 diabetic nephropathy and can be administered as a safe adjuvant therapy for these patients.

Topics: Administration, Oral; Curcuma; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Dietary Supplements; Double-Blind Method; Female; Humans; Interleukin-8; Male; Middle Aged; Phytotherapy; Proteinuria; Transforming Growth Factor beta; Tumor Necrosis Factor-alpha

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

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

The current study aimed to identify the molecular mechanisms of a metal mixture (cadmium, nickel, and lead) involved in type 2 diabetes mellitus (T2DM) development and the therapeutic effect of curcumin in this metal mixture-induced T2DM. To accomplish this, SwissADME assessed the physicochemical and pharmacokinetic properties of curcumin and the Prediction of Activity Spectra for Substances evaluates its biological activities. The Comparative Toxicogenomics Database, Cytoscape, AutoDock Vina, and MicroRNA ENrichment TURned NETwork were used as tools to perform data-mining approaches and molecular docking. Curcumin properties were fitted within the acceptable range to be a promising drug candidate. The mixed metal altered 23 genes linked to T2DM development and targeted by curcumin. Curcumin had a dual-natured effect or antagonistic effect for most of the involved genes in T2DM and metal mixture. The most prominent biological processes were identified as ''response to external stimulus'', ''regulation of programmed cell death'', ''programmed cell death'', ''cell death'', and ''response to stress''. Three highly interacted miRNAs related to metal mixture-induced T2DM and targeted by curcumin (hsa-miR-98-5p, hsa-miR-34a-5p, and hsa-miR-155-5p) were identified. These findings could pave the way for further studies to evaluate the link between these genes and T2DM.

Topics: Curcumin; Diabetes Mellitus, Type 2; Humans; MicroRNAs; Molecular Docking Simulation; Seizures

Type 2 diabetes mellitus (T2DM) is a disease characterized by a prolonged hyperglycemic condition caused by insulin resistance mechanisms in muscle and liver, reduced insulin production by pancreatic β cells, and a chronic inflammatory state with increased levels of the pro-inflammatory marker semaphorin 3E. Phytochemicals present in several foods have been used to complement oral hypoglycemic drugs for the management of T2DM. Notably, dipeptidyl peptidase IV (DPPIV) inhibitors have demonstrated efficacy in the treatment of T2DM. Our study aimed to investigate, in in vitro models of insulin resistance, the ability of the flavanones naringenin and hesperetin, used alone and in combination with the anti-inflammatory natural molecules curcumin, polydatin, and quercetin, to counteract the insulin resistance and pro-inflammatory molecular mechanisms that are involved in T2DM development. Our results show for the first time that the combination of naringenin, hesperetin, curcumin, polydatin, and quercetin (that mirror the nutraceutical formulation GliceFen

Topics: Curcumin; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Flavanones; Humans; Insulin; Insulin Resistance; Quercetin; Semaphorins

Successful management of type 2 diabetes mellitus (T2DM), a complex and chronic disease, requires a combination of anti-hyperglycemic and anti-inflammatory agents. Here, we have conceptualized and tested an integrated "closed-loop mimic" in the form of a glucose-responsive microgel (GRM) based on chitosan, comprising conventional insulin (INS) and curcumin-laden nanoparticles (nCUR) as a potential strategy for effective management of the disease. In addition to mimicking the normal, on-demand INS secretion, such delivery systems display an uninterrupted release of nCUR to combat the inflammation, oxidative stress, lipid metabolic abnormality, and endothelial dysfunction components of T2DM. Additives such as gum arabic (GA) led to a fivefold increased INS loading capacity compared to GRM without GA. The GRMs showed excellent in vitro on-demand INS release, while a constant nCUR release is observed irrespective of glucose concentrations. Thus, this study demonstrates a promising drug delivery technology that can simultaneously, and at physiological/pathophysiological relevance, deliver two drugs of distinct physicochemical attributes in the same formulation.

Topics: Chitosan; Curcumin; Diabetes Mellitus, Type 2; Glucose; Humans; Insulin; Insulin, Regular, Human; Microgels; Nanoparticles

Liquid self-nanoemulsifying drug delivery system (L-SNEDDS) of curcumin and quercetin were prepared by dissolving them in isotropic mixture of Labrafil M1944CS®, Capmul MCM®, Tween-80® and Transcutol P®. The prepared L-SNEDDS were solidified using Ganoderma lucidum extract, probiotics and Aerosil-200® using spray drying. These were further converted into pellets using extrusion-spheronization. The mean droplet size and zeta potential of L-SNEDDS were found to be 63.46 ± 2.12 nm and - 14.8 ± 3.11 mV while for solid SNEDDS pellets, these were 72.46 ± 2.16 nm and -38.7 ± 1.34 mV, respectively. The dissolution rate for curcumin and quercetin each was enhanced by 4.5 folds while permeability was enhanced by 5.28 folds (curcumin) and 3.35 folds (quercetin) when loaded into SNEDDS pellets. The Cmax for curcumin and quercetin containing SNEDDS pellets was found 532.34 ± 5.64 ng/mL and 4280 ± 65.67 ng/mL, respectively. This was 17.55 and 3.48 folds higher as compared to their naïve forms. About 50.23- and 5.57-folds increase in bioavailability was observed for curcumin and quercetin respectively, upon loading into SNEDDS pellets. SNEDDS pellets were found stable at accelerated storage conditions. The developed formulation was able to normalize the levels of blood glucose, lipids, antioxidant biomarkers, and tissue architecture of pancreas and liver in streptozotocin induced diabetic rats as compared to their naïve forms.

Topics: Administration, Oral; Animals; Biological Availability; Curcumin; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Drug Delivery Systems; Emulsions; Nanoparticles; Particle Size; Powders; Probiotics; Quercetin; Rats; Reishi; Solubility; Streptozocin

Diabetes mellitus (DM) is one of the most common complications in patients with ulcerative colitis (UC). Curcumin has a wide range of bioactive and pharmacological properties and is commonly used as an adjunct to the treatment of UC and DM. However, the role of curcumin in UC complicated by DM has not been elucidated. Therefore, this study was conducted to construct a model of UC complicating diabetes by inducing UC in DB mice (spontaneously diabetic) with dextran sodium sulfate. In this study, curcumin (100 mg/kg/day) significantly improved the symptoms of diabetes complicated by UC, with a lower insulin level, heavier weight, longer and lighter colons, fewer mucosal ulcers and less inflammatory cell infiltration. Moreover, compared to untreated DB mice with colitis, curcumin-treated mice showed weaker Th17 responses and stronger Treg responses. In addition, curcumin regulated the diversity and relative abundance of intestinal microbiota in mice with UC complicated by DM at the phylum, class, order, family and genus levels. Collectively, curcumin effectively alleviated colitis in mice with type 2 diabetes mellitus by restoring the homeostasis of Th17/Treg and improving the composition of the intestinal microbiota.

Topics: Animals; Colitis; Colitis, Ulcerative; Colon; Curcumin; Dextran Sulfate; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Disease Models, Animal; Gastrointestinal Microbiome; Homeostasis; Humans; Mice; Mice, Inbred C57BL; T-Lymphocytes, Regulatory

Topics: Animals; Antioxidants; Arachidonic Acid; Biomarkers; Chromatography, High Pressure Liquid; Curcumin; Diabetes Mellitus, Type 2; Liver; Metabolomics; Mice

Curcumin has been suggested as a promising treatment for metabolic diseases, but the high doses required limit its therapeutic use. In this study, a new curcuminoid is synthesised to increase curcumin anti-inflammatory and antioxidant potential and to achieve hypoglycaemic and protective vascular effects in type 2 diabetic rats in a lower dose. In vitro, the anti-inflammatory effect was determined through the Griess reaction, and the antioxidant activity through ABTS and TBARS assays. In vivo, Goto-Kakizaki rats were treated for 2 weeks with the equimolar dose of curcumin (40 mg/kg/day) or curcuminoid (52.4 mg/kg/day). Fasting glycaemia, insulin tolerance, plasma insulin, insulin signalling, serum FFA, endothelial function and several markers of oxidative stress were evaluated. Both compounds presented a significant anti-inflammatory effect. Moreover, the curcuminoid had a marked hypoglycaemic effect, accompanied by higher GLUT4 levels in adipose tissue. Both compounds increased NO-dependent vasorelaxation, but only the curcuminoid exacerbated the response to ascorbic acid, consistent with a higher decrease in vascular oxidative and nitrosative stress. SOD1 and GLO1 levels were increased in EAT and heart, respectively. Altogether, these data suggest that the curcuminoid developed here has more pronounced effects than curcumin in low doses, improving the oxidative stress, endothelial function and glycaemic profile in type 2 diabetes.

Topics: Animals; Antioxidants; Blood Glucose; Curcumin; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Diarylheptanoids; Disease Models, Animal; Hypoglycemic Agents; Insulin; Rats

We aimed to identify the molecular mechanisms behind curcumin's therapeutic benefits for metabolic syndrome (MetS) and its components.. The Comparative Toxicogenomics Database, MIENTURNET, Metascape, GeneMania, and Cytoscape software were critical analytic tools.. Curcumin may have therapeutic effects on MetS and its components via the following genes: NOS3, IL6, INS, and ADIPOQ, particularly PPARG. Curcumin has higher docking scores than other genes with INS and PPARG (docking scores: -8.3 and -5.8, respectively). Physical interactions (56%) were found to be the most prevalent for dyslipidemia, co-expression for hypertension, obesity, T2DM, and MetS. "Galanin receptor pathway", "lipid particles composition", "IL-18 signaling pathway", "response to extracellular stimulus", and "insulin resistance" were listed in the first of the key pathways for MetS, dyslipidemia, hypertension, obesity, and diabetes, respectively. The protein-protein interaction enrichment analysis study also identified "vitamin B12 metabolism," "folate metabolism," and "selenium micronutrient network" as three major molecular pathways linked to MetS targeted by curcumin. PPARG was the key transcription factor that regulated practically all curcumin-targeted genes linked to MetS and its components. Curcumin targeted hsa-miR-155-5p, which has been linked to T2DM, hypertension, and MetS, as well as hsa-miR-130b-3p and hsa-miR-22-3p, which have been linked to dyslipidemia and obesity, respectively. In silico, sponges that regulated hsa-miR-155-5p were developed and evaluated. Curcumin, MetS, and its components have been found to target adipocytes, cardiac myocytes, smooth muscle, the liver, and pancreas. Curcumin's physicochemical properties and pharmacokinetics are closely connected with its therapeutic advantages in MetS and its components due to its high gastrointestinal absorption, drug-likeness, water solubility, and lipophilic nature. Curcumin is a CYP1A9 and CYP3A4 inhibitor. Although curcumin has a low bioavailability, it can be synthesized and administered to increase its pharmacokinetic features.. Curcumin needs to undergo therapeutic optimization and further study into its pharmacological structure before it can be used to treat MetS and its components.

Topics: Curcumin; Diabetes Mellitus, Type 2; Humans; Hypertension; Metabolic Syndrome; MicroRNAs; Obesity; PPAR gamma; Transcription Factors

Streptozotocin (STZ)-induced diabetes rodent models are widely used to study the pathogenesis and metabolic function in diabetes (DM). The aim of this study was to assess the antioxidant effect of curcumin in STZ-induced type 2 diabetes mellitus (T2DM). In this research, rats were randomly divided into 3 groups (8 in each group): a nondiabetic group (Control), a diabetic group (DM), and a curcumin treatment group (DM + Cur 200 mg/kg group). Meanwhile, after intraperitoneal injection (i.p.), associated-oxidative stress parameters were observed, malondialdehyde (MDA) was decreased, and glutathione peroxidase (GPX) and super oxide dismutase (SOD) were restored in pancreatic tissues of curcumin-treated DM rats. In addition, curcumin improved the survival and function of islet cells with decreased cell apoptosis in Langerhans islet and increased insulin secretion in the STZ-induced T2DM rat model. Our findings suggest that curcumin is a potent candidate for the prevention and therapy of DM.

Topics: Animals; Antioxidants; Blood Glucose; Curcumin; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Islets of Langerhans; Rats; Rats, Wistar; Streptozocin

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

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

Type 2 diabetes mellitus (T2DM) is an ensemble of metabolic diseases that has reached pandemic dimensions all over the world. There is a lack of evidence on the contribution of curcumin in the treatment of T2DM. We conducted a protocol for systematic review and meta-analysis to evaluate whether curcumin supplementation is effective and safe in T2DM patients.. The systematic review will follow the guidelines of Preferred Reporting Items for Systematic Reviews and Meta-analyses Protocols (PRISMA-P). We will obtain studies through PubMed, Cochrane Library, Embase, Web of Science, and Medline databases. In addition, we will also collect 4 databases of China: China National Knowledge Infrastructure, China Biomedical Literature Database, China Science Journal Database, and Wan-fang Database. Eligible study conference abstracts and reference lists of manuscripts will be searched. The data collection and analysis will be conducted independently by 2 reviewers. Meta-analysis will be performed using Review Manager software, version 5.3 (Update Software Ltd, Oxford, Oxon, UK).. The results of this systematic review and meta-analysis will be published in a peer-reviewed journal.. The findings of this systematic review may encourage supplementation of curcumin and its preparation specifically in T2DM patients. Nevertheless, the application of curcumin supplementation in clinical practice should be taken with individual's contributing factors.

Topics: Adiponectin; C-Reactive Protein; Curcumin; Diabetes Mellitus, Type 2; Dietary Supplements; Humans; Lipids; Meta-Analysis as Topic; Research Design; Systematic Reviews as Topic

Diabetes is a chronic disorder affecting a large number of people throughout the world. According to the American Diabetes Association, overeating is the major diet-related risk factor for type 2 diabetes. To ensure the efficacy of C. longa. in the improvement of glycemic control, neuropathic sensation, and reduction in the formation of advanced glycation end products 90 people that meet inclusion criteria were divided into 2 groups, the control group was only given antidiabetic drugs without C. longa supplement and the treatment group were given C. longa supplement as well as recommended hypoglycemic drugs for 120 days. Results reveal that in all combinations of antidiabetic medicine the addition of curcumin has significantly reduced the level of hemoglobin A

Topics: Blood Glucose; Curcuma; Diabetes Mellitus, Type 2; Glycation End Products, Advanced; Humans; Hypoglycemic Agents; Peripheral Nervous System Diseases; Sensation

Activation of the intrarenal renin-angiotensin system (RAS) is implicated in the pathogenesis of kidney injury and hypertension. We aimed to investigate the protective effect of tetrahydrocurcumin (THU) on intrarenal RAS expression, kidney injury, and systolic blood pressure (SBP) in high-fat diet (HFD)-induced type 2 diabetic mice.. Eight-week-old male mice were fed a regular diet (RD) or HFD for 12 weeks, and THU (50 or 100 mg/kg/day) was intragastrically administered with HFD. Physiological and metabolic changes were monitored and the expression of RAS components and markers of kidney injury were assessed.. HFD-fed mice exhibited hyperglycemia, insulin resistance, and dyslipidemia compared to those in the RD group (P<0.05). Kidney injury in these mice was indicated by an increase in the ratio of albumin to creatinine, glomerular hypertrophy, and the effacement of podocyte foot processes. Expression of intrarenal angiotensin-converting enzyme, angiotensin II type I receptor, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-4, and monocyte chemoattractant protein-1 was also markedly increased in HFD-fed mice. HFD-fed mice exhibited elevated SBP that was accompanied by an increase in the wall thickness and vascular cross-sectional area (P<0.05), 12 weeks post-HFD consumption. Treatment with THU (100 mg/kg/day) suppressed intrarenal RAS activation, improved insulin sensitivity, and reduced SBP, thus, attenuating kidney injury in these mice.. THU alleviated kidney injury in mice with HFD-induced type 2 diabetes, possibly by blunting the activation of the intrarenal RAS/nicotinamide adenine dinucleotide phosphate oxidase IV (NOX4)/monocyte chemoattractant protein 1 (MCP-1) axis and by lowering the high SBP.

Topics: Animals; Blood Pressure; Curcumin; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Diet, High-Fat; Kidney; Male; Mice

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

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

Type 2 diabetes mellitus (T2DM) is known as a complex genetic disease characterized by genetic and environmental factors. The imbalanced intestinal flora and intestinal mucosal barrier are considered to be related to T2DM. Curcumin has been proved to affect the progression of T2DM. T2DM animal was established by low-dose streptozotocin intraperitoneal injection combined with high-fat diet (HFD) feeding. Hematoxylin and eosin (HE) staining and transfer electron microscopy (TEM) were used to observe morphological changes of intestinal tissues of T2DM rats. Insulin and glucose tolerance tests were performed to investigate the influence of curcumin on blood glucose. Curcumin significantly improved the intestinal integrity, hyperglycemia and insulin resistance in diabetic rats. The metabolic endotoxemia induced by HFD in diabetic rats was inhibited remarkably. Curcumin reversed gut microbiota dysbiosis in diabetic rats caused by HFD. We demonstrated that curcumin could protect intestinal mucosal barrier, improve insulin resistance and reduce blood glucose in diabetic rats. This study might provide experimental evidence for the prevention and treatment in T2DM.

Topics: Animals; Bacteroidetes; Bifidobacterium; Curcumin; Diabetes Mellitus, Type 2; Diet, High-Fat; Endotoxemia; Firmicutes; Gastrointestinal Microbiome; Gene Ontology; Hyperglycemia; Insulin Resistance; Intestines; Lipopolysaccharides; Metabolomics; Mice; NF-kappa B; Rats; Signal Transduction; Tight Junction Proteins; Toll-Like Receptor 4; Tumor Necrosis Factor-alpha

We evaluated the efficacy of curcumin administration on blood glucose levels and its relationship with nesfatin-1 levels in blood brain and adipose tissue of streptozotocin-induced diabetic rats.. A total of 28 male rats were divided into four groups: control group, type 2 diabetes mellitus (DM) group, control plus curcumin group and type 2DM plus curcumin group. After fifteen days, blood samples were collected from sacrificed rats. Nesftain-1 levels were analysed from blood, brain, and fat tissues of rats in all groups.. Nesfatin-1 level was found to be significantly lower in blood, brain and fat tissues of type 2 DM rats compared to the control group. A significant decrease in fasting blood glucose levels was observed in the curcumin administration group compared to type 2 DM group. Improvement of fasting blood glucose level was accompanied by improvement of nesfatin-1 levels in blood, brain, and fat tissues.. As expected, curcumin administration caused significant improvement in fasting blood glucose levels. However, for the first time, we found marked improvements in nesfatin-1 levels in blood, brain, and fat tissues of type 2 DM rats. Thus, considering the crucial role of nesfatin-1 in regulation of glucose metabolism, it is logical to expect an interactive relationship between curcumin and nesfatin-1.

Topics: Adipose Tissue; Animals; Brain; Curcumin; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Injections, Intraperitoneal; Male; Nucleobindins; Rats; Rats, Wistar; Streptozocin

The potentiality of Stevia leaves and turmeric roots as remedies against diabetes mellitus type 2 was tested in this study. Stevia leaves and turmeric roots were extracted with ethanol:water (80:20 v/v) and analyzed by HPLC. Turmeric extract (TUE) was rich in; curcumin, gallic acid, and eugenol. Stevia extract (STE) contained 28 known compounds, including glycosides, aromatic organic acids, and catechin. Fifty rats were divided into five groups (10 rats each); the control group were fed with feed and water ad libitum. Forty rats were injected a single dose of alloxan, then treated with either 10 mg/kg glibenclamide (GLI), 300 mg/kg STE, or 200 mg/kg TUE or water (positive control) through daily gastric oral gavages for 56 days. Treating diabetic rats with TUE significantly reduced serum glucose and glycated hemoglobin down to the negative control levels. Both GLI and STE produced similar but less effective actions. Animals treated with either STE or TUE exhibited reduced levels of liver and kidney markers compared to the negative control, while GLI increased them significantly. It could be concluded that turmeric roots and stevia leaves extracts can be used treatment for type 2 diabetes. PRACTICAL APPLICATIONS: Turmeric roots and stevia leaves extracts may be used as a remedy for type 2 diabetic patients as aiding substituting treatments under medical supervision. The two plant sources can be used as raw materials for the extracts, which can be used under medical supervision as a gradual replacement of the synthetic antidiabetic drugs. These extracts can be used after a preliminary clinical study to determine the dose and frequency of administration. Stevia extract can be incorporated in drinks as a sweetener and drug. Turmeric extract has a bitter taste, so it may be incorporated in some foods such as bread, which is a traditional practice in some kinds of bread in Egypt. But its content in the bread and the acceptability of the taste should be adjusted. Alternatively, this food can incorporate both TUE and STE to get the best biological action and to conceal the bitter taste of turmeric.

Topics: Animals; Curcuma; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Plant Extracts; Rats; Stevia

To study the effect of curcumin on the expression of glucose regulated protein 78 kD(GRP78) and cysteinyl aspartate specific proteinase-12(caspase-12) of myocardial endoplasmic reticulum stress related factors in type 2 diabetes rats.. Type 2 diabetes rats model was established by high-fat drink feeding and one-time intraperitoneal injecting streptozotocin(35 mg/kg). After model rats were built, rats was randomly divided into diabetic model group and low dose of curcumin group(200 mg/kg), high dose of curcumin group(400 mg/kg) and captopril group(60 mg/kg) with 10 rats in each group. The rats in each group were ig administered with corresponding drugs once a day. Continuous administration for 12 w. The levels of fasting blood glucose(FBG) and lactate dehydrogenase(LDH), electrocardiogram and heart weight index(HWI) were measured respectively. The myocardial pathological changes were observed by HE staining. The levels of collagen fiber expression in myocardial tissue were performed by Masson staining. The protein expression levels of GRP78 and caspase-12 in myocardium of rats were observed by immunohistochemistry.. The result showed that compared with control group, the levels of FBG and LDH of serum were increased obviously, HWI was increased, myocardial cells were hypertrophy, the collagen fibers of intercellular space of cell were increased, the protein expressions of GRP78 and caspase-12 of myocardium were increased in rats, myocardial cell apoptosis was increased in the model group(P<0. 05). Compared with model group, FBG and LDH levels and HWI were reduced, the collagen fiber of intercellular space were decreased, the protein expression levels of GRP78 and caspase-12 were lowered in high dose of curcumin group(P<0. 05).. It indicates that Cur defends myocardium tissue in type 2 diabetes rats, which may be related to decreasing the level of blood glucose and the protein expressions of GRP78 and caspase-12, and blocking the ERS-initiated apoptotic.

Topics: Animals; Apoptosis; Blood Glucose; Caspase 12; Curcumin; Diabetes Mellitus, Type 2; Endoplasmic Reticulum Stress; Heart; Heat-Shock Proteins; Myocardium; Random Allocation; Rats

Type 2 diabetes mellitus (DM)-induced cardiomyopathy is a multifactorial and complex disease involving oxidative stress, lipids, and fibrosis. It is based on metabolic disorders and microvascular disease and causes extensive focal necrosis of the heart muscle. Curcumin (CUR) is a natural polyphenol isolated from turmeric rhizomes and plays an important role in the antioxidant, anti-apoptotic and anti-inflammatory effects of diabetes. Therefore, we established a mouse model of diabetic cardiomyopathy (DCM) in type 2 diabetic db/db mice in our study. We divided the experiment into three groups: the control group, DM group and DM + CUR group.We performed cardiac dissection on mice treated in different conditions and conducted special pathological staining on isolated cardiac tissue. We were surprised to find that a high glucose environment can promote cardiomyocyte apoptosis by TUNEL assay. In addition, after detecting dihydroethiidine (DHE), hematoxylin-eosin (H&E) and Oil Red O staining, we unexpectedly found that CUR can inhibit the production of reactive oxygen species (ROS), reduce myocardial apoptosis, and myocardial lipid accumulation. CUR upregulated the expression of Bcl-2, and downstream the expression of Bax and Caspase-3 proteins by immunohistochemical determination and western blotting. Therefore, these results suggest that CUR has a certain protective effect on diabetic cardiomyopathy by inhibiting the production of ROS.

Topics: Animals; Antioxidants; Cardiotonic Agents; Curcumin; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Diabetic Cardiomyopathies; Male; Mice; Mice, Inbred C57BL; Oxidative Stress; Reactive Oxygen Species

This study aimed to investigate the therapeutic effect of curcumin on type 2 diabetes and its underlying mechanisms. A type 2 diabetes mellitus rat model was established by providing high-fat diet and low doses of streptozotocin. Type 2 diabetes mellitus rats were treated with low dose and high dose of curcumin for 8 weeks. The results showed that high-dose curcumin significantly reduced fasting blood glucose, total cholesterol, triglyceride, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, alanine aminotransferase, and aspartate transaminase, liver coefficient, and malondialdehyde levels, and BCL2-Associated X expression in the type 2 diabetes mellitus rats. High-dose curcumin increased the levels of liver superoxide dismutase, catalase, and glutathione; as well as the expression of liver B-cell lymphoma-2, phosphatidylinositol 3-kinase, phosphorylated phosphatidylinositol 3-kinase, protein kinase B, and phosphorylated protein kinase B in type 2 diabetes mellitus rats. Furthermore, it ameliorated the histological structure of the liver and pancreas in diabetes mellitus model rats. However, low-dose curcumin had no significant effect on diabetes mellitus model rats. The results suggest that adequate doses of curcumin controls type 2 diabetes mellitus development as well as the mechanism involved in its anti-apoptotic actions and phosphatidylinositol 3-hydroxy kinase/protein kinase B signal pathway regulation in the liver.

Topics: Animals; Apoptosis; Blood Glucose; Body Weight; Curcumin; Diabetes Mellitus, Type 2; Disease Models, Animal; Glucose Tolerance Test; Hypoglycemic Agents; Lipids; Liver; Male; Organ Size; Oxidative Stress; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Rats; Rats, Sprague-Dawley; Signal Transduction

Protein tyrosine phosphatase (PTP1B) is a potential target for the treatment of type 2 diabetes and cancer. Curcumin and cinnamaldehyde have been previously reported to have antidiabetic and anticancer potentials. The aim of this study was to investigate the effect of curcumin in comparison to cinnamaldehyde on the enzymatic activity of PTP1B and the viability of MCF-7 cancer cells.. Enzymatic activity and cell viability assays were utilized. Experiments were performed using the breast cancer MCF-7 cell line.. Curcumin and cinnamaldehyde decreased the activity of PTP1B, and had inhibitory effects on the viability of MCF-7 cancer cells. Curcumin had a significantly higher inhibitory effect than cinnamaldehyde.. Curcumin can be considered a potential agent for the treatment of type-2 diabetes or cancer.

Topics: Acrolein; Antineoplastic Agents; Breast Neoplasms; Cell Survival; Curcumin; Diabetes Mellitus, Type 2; Drug Screening Assays, Antitumor; Female; Humans; Hypoglycemic Agents; MCF-7 Cells; Protein Tyrosine Phosphatase, Non-Receptor Type 1

To investigate the intervention of curcumin and its analogue J7 on oxidative stress injury in testis of type 2 diabetic rats.. Sixty male SD rats, 10 rats were chosen as normal control group (NC), the other 50 rats were assigned to experiment group. Experiment diabetic rats were induced by high-fat food and intraperitoneal injection of steptozotocin (STZ). After the model was established successfully, diabetic rats were divided into four groups randomly: diabetes mellitus group (DM, n=12), curcumin treatment group (CUR, n=10), high dose treatment group of J7 (J+, n=10), low dose treatment group of J7 (J-, n=10). The CUR group were intragastrically administered with curcumin 20 mg/kg daily, in addition, the J+ group and the J- group were intragastrically administered with J7 20 mg/kg and 10 mg/kg daily respectively. After 8 weeks, the fast blood glucose was detected biochemically. The activity of superoxide dismutase (SOD) and the level of malondialdehyde (MDA) were detected by hydroxylamine method and thiobarbituric acid method respectively. The protein expressions of the nuclear factor-erythroid 2-related factor 2 (tNrf2), phosphorylation of Nrf2 (pNrf2), catalase (CAT), NAD(P)H quinine oxidoreductase 1 (NQO1) were measured by Western blot. The mRNA expressions of CAT, NQO1, hemeoxygenase-1 (HO1) were measured by quantitative real-time PCR (qRT-PCR). Morphological structure of testis was observed by hematoxylin-eosin (HE) staining. The expressions of Nrf2 and CAT were also detected by immunohistochemical method.. The levels of fast blood glucose and MDA in DM group were increased significantly(P＜0.05), while the body weight, the activity of SOD, the protein expressions of pNrf2/tNrf2, CAT, NQO1 and the mRNA expressions of CAT, NQO1, HO1 were decreased (P＜0.05). Under light microscope, the DM group showed disrupted histological appearance. Immunohistochemistry showed that the protein expressions of Nrf2 around the nucleus and CAT were decreased. With the treatment of curcumin and J7, the MDA levels in the three treatment groups were decreased (P＜0.05). The activity of SOD, the protein expressions of pNrf2/tNrf2, CAT, NQO1 and the mRNA expressions of NQO1, HO1 were increased (P＜0.05). the levels of fast blood glucose were decreased in the J+ and J- group (P＜0.05), and the mRNA expression of CAT was increased in the J+ group (P＜0.05). The ratio of pNrf2/tNrf2 in the J+ group was significantly higher than that in CUR and J- group (P＜0.05). The protein level of CAT in the J+ group was also significantly higher than that in J- group (P＜0.05). There were no significant differences in other indexes among the three treatment groups. Under light microscope, the morphology was obviously improved in the three treatment groups. Immunohistochemistry showed that the protein expressions of Nrf2 around the nucleus and CAT were increased in the three treatment groups. It was suggested that high dose J7 had better antioxidant stress ability in testis of diabetic rats.. Curcumin and J7 could inhibit the oxidative stress damage of testicular tissue in diabetic rats, which might be related with the activation of the Nrf2-ARE signaling pathway.

Topics: Animals; Blood Glucose; Curcumin; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Male; Malondialdehyde; NF-E2-Related Factor 2; Oxidative Stress; Random Allocation; Rats; Rats, Sprague-Dawley; Signal Transduction; Superoxide Dismutase; Testis

B6, an analog of curcumin, is a compound isolated from a traditional Chinese medicine Turmeric. In this paper, we aimed to explore the efficacy of B6 on diabetic nephropathy and the related mechanisms.. The effects of B6 were studied on fast-blood glucose, serum creatinine, urea nitrogen, urine albumen/24 h, pathological changes of main organs, the levels of ACE2 and ACE2 mRNA in the rat model of diabetes induced by streptozotocin.. The results showed that B6 treatment could reduce serum creatinine, urea nitrogen, urine albumen/24 h, decrease the level of AngII, improve the renal pathological changes in diabetic rats and increase the levels of ACE2 and ACE2 mRNA.. These results suggested B6 could protect the renal function of diabetic rats. This study provided scientific basis for the further researches and clinical applications of B6.

Topics: Angiotensin-Converting Enzyme 2; Animals; Curcumin; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Male; Peptidyl-Dipeptidase A; Rats; Rats, Wistar; RNA, Messenger; Streptozocin

Curcumin, a naturally occurring anti-inflammatory compound, has shown promise in pre-clinical studies to treat erectile dysfunction (ED) associated with type-1 diabetes. However, poor bioavailability following oral administration limits its efficacy. The present study evaluated the potential of topical application of curcumin-loaded nanoparticles (curc-np) to treat ED in a rat model of type-2 diabetes (T2D).. Determine if topical application of curc-np treats ED in a T2D rat model and modulates expression of inflammatory markers.. Curc-np (4 mg curcumin) or blank nanoparticles were applied every 2 days for 2 weeks to the shaved abdomen of 20-week-old Zucker diabetic fatty male rats (N = 5 per group). Lean Zucker diabetic fatty male rat controls were treated with blank nanoparticles (N = 5). Penetration of nanoparticles and curcumin release were confirmed by 2-photon fluorescence microscopy and histology. Erectile function was determined by measuring intracorporal pressure (ICP) normalized to systemic blood pressure (ICP/BP) following cavernous nerve stimulation. Corporal tissue was excised and reverse transcription and quantitative polymerase chain reaction used to determine expression of the following markers: nuclear factor (NF)-κβ, NF-κβ-activating protein (Nkap), NF erythroid 2-related factor-2, Kelch-like enoyl-CoA hydratase-associated protein-1, heme oxygenase-1 (HO-1), variable coding sequence-A1, phosphodiesterase-5, endothelial and neuronal nitric oxide synthase, Ras homolog gene family member A, and Rho-associated coiled-coil containing protein kinases-1 and -2.. Erectile function by determination of ICP/BP and expression of molecular markers in corporal tissue by RT-qPCR.. Nanoparticles penetrated the abdominal epidermis and persisted in hair follicles for 24 hours. Curc-np-treated animals exhibited higher average ICP/BP than animals treated with blank nanoparticles at all levels of stimulation and this was statistically significant (P < .05) at 0.75 mA. In corporal tissue, Nkap expression decreased 60% and heme oxygenase-1 expression increased 60% in curc-np- compared to blank nanoparticle-treated animals. ICP/BP values inversely correlated with Nkap and directly correlated with HO-1 expression levels.. These studies demonstrate the potential for topical application of curc-np as a treatment for ED in T2D patients.. The T2D animal model of ED represents a more prevalent disease than the more commonly studied type-1 diabetes model. Although there is improved erectile response in curc-np-treated animals, only at the lower levels of stimulation (0.75 mA) was this significant compared to the blank nanoparticle-treated animals, suggesting more studies are needed to optimize protocols and evaluate toxicity. Topical application of curc-np to a rat model of T2D can systemically deliver curcumin, treat ED, and modulate corporal expression of inflammatory markers. Draganski A, Tar MT, Villegas G, et al. Topically Applied Curcumin-Loaded Nanoparticles Treat Erectile Dysfunction in a Rat Model of Type-2 Diabetes. J Sex Med 2018;15:645-653.

Topics: Administration, Topical; Animals; Curcumin; Cyclic Nucleotide Phosphodiesterases, Type 5; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Drug Delivery Systems; Endothelium; Erectile Dysfunction; Heme Oxygenase (Decyclizing); Male; Nanoparticles; NF-E2-Related Factor 2; NF-kappa B; Nitric Oxide Synthase; Nitric Oxide Synthase Type I; Penile Erection; Penis; Protein Precursors; Rats; Rats, Zucker; Salivary Proteins and Peptides

Excessive reactive oxygen species production caused by type 2 diabetes conditions can disrupt normal bone metabolism and greatly impair bone regeneration.. In the present study, curcumin (Cur)-loaded microspheres were incorporated into a fish collagen nano-hydroxyapatite scaffold to promote bone repair under diabetic conditions by inhibiting the reactive oxygen species production.. The drug release kinetic study showed that the Cur release from the composite scaffolds lasted up to 30 days. The sustained curcumin release from the scaffold significantly inhibited the overproduction of reactive oxygen species in mesenchymal stem cells caused by diabetic serum. Moreover, the Cur-loaded scaffold also remarkedly alleviated the negative effects of diabetic serum on the proliferation, migration, and osteogenic differentiation of mesenchymal stem cells. When implanted into bone defects in type 2 diabetic rats, the Cur-loaded scaffold also showed a greater bone formation capability compared to the pure scaffold.. The results of this study suggested that the novel controlled Cur release system may provide a promising route to improve bone regeneration in type 2 diabetic patients.

Topics: Animals; Bone Marrow; Bone Regeneration; Cell Movement; Cell Proliferation; Cell Survival; Cells, Cultured; Curcumin; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Male; Mesenchymal Stem Cells; Microspheres; Polylactic Acid-Polyglycolic Acid Copolymer; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species; Structure-Activity Relationship

Development of curcumin-loaded mixed polymeric micelles based on chitosan, alginate, maltodextrin, pluronic F127, pluronic P123, and tween 80, by thin-film hydration method has been investigated in Bisphenol A induced diabetics rats. Curcumin (C

Topics: Alginates; Animals; Biological Availability; Blood Glucose; Chitosan; Curcumin; Diabetes Mellitus, Type 2; Drug Carriers; Hypoglycemic Agents; Insulin-Secreting Cells; Micelles; Poloxalene; Poloxamer; Polysaccharides; Polysorbates; Rats; Wound Healing

Diabetes mellitus is a metabolic disorder in which a person has high blood glucose levels due to inadequate insulin production by the pancreas. Wounds in these individuals cannot heal properly over time due to circulatory changes that hinder and stagnate the healing process. We report the case of an 82-year-old female type 2 diabetes mellitus carrier, presenting to clinical-dermatological examination pressure ulcer (PU) in the right calcaneus region. The patient was treated with photodynamic therapy using curcumin and blue light-emitting diodes (LEDs), laser therapy, and the application of a cellulose membrane in order to promote ulcer decontamination by local action, accelerate wound healing, and maintain favorable conditions of asepsis and moisture, respectively. The ulcer healing occurred after 30days of treatment and total epithelialization was observed. From the results obtained in this case report, we conclude that the combination of photodynamic therapy, laser therapy, and coating with a cellulose membrane is a promising treatment for the healing of PU in diabetic patients.

Topics: Aged, 80 and over; Combined Modality Therapy; Curcumin; Diabetes Mellitus, Type 2; Diabetic Foot; Female; Heel; Humans; Low-Level Light Therapy; Photochemotherapy; Photosensitizing Agents; Pressure Ulcer; Wound Healing

To investigate the protective effect of curcumin analogue L6H4 on the kidney from the type 2 diabetic rats.. The levels of the 24 h urinary protein, FBG, TG, Scr and BUN were elevated significantly in diabetic group(. L6H4 exerts the protective effect on kidneys of type 2 diabetic rats by reducing expression of TGF-β1, inhibiting secretion of Col-IV and FN, relieving the deposition of the extracellular matrix.

Topics: Animals; Blood Glucose; Blood Urea Nitrogen; Collagen Type IV; Creatinine; Curcumin; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Extracellular Matrix; Fibronectins; Kidney; Male; Rats; Rats, Sprague-Dawley; Transforming Growth Factor beta1; Triglycerides; Uric Acid

Oxidative stress has a key role in the pathogenesis of type II diabetes mellitus (T2DM) and its vascular complications. Antioxidant therapy has been suggested as a potential approach to blunt T2DM development and progression. The aim of this study was to assess the effects of supplementation with curcuminoids, which are natural polyphenolics from turmeric, on oxidative indices in diabetic individuals.. In this randomized double-blind placebo-controlled trial, 118 subjects with T2DM were randomized to curcuminoids (1000 mg/day co-administered with piperine 10 mg/day) or matching placebo for a period of 8 weeks. Serum total antioxidant capacity, superoxide dismutase (SOD) activities and malondialdehyde (MDA) concentrations were measured at baseline and after the supplementation period.. Curcuminoids supplementation caused a significant elevation in serum total antioxidant capacity (TAC) (p < 0.001) and SOD activities (p < 0.001), while serum MDA levels were significantly reduced compared with the placebo group (p < 0.001). These results remained statistically significant after adjustment for potential confounders (baseline differences in body mass index and fasting serum insulin).. The present results support an antioxidant effect of curcuminoids supplementation in patients with T2DM, and call for future studies to assess the impact of these antioxidant effects on the occurrence of diabetic complications and cardiovascular endpoints.

Topics: Adult; Antioxidants; Blood Glucose; Curcuma; Curcumin; Diabetes Mellitus, Type 2; Dietary Supplements; Double-Blind Method; Female; Follow-Up Studies; Humans; Male; Middle Aged; Oxidative Stress; Treatment Outcome

Diabetic nephropathy is a serious complication of type 2 diabetes mellitus, and delaying the development of diabetic nephropathy in patients with diabetes mellitus is very important. In this study, we investigated inflammation, oxidative stress, and lipid metabolism to assess whether curcumin ameliorates diabetic nephropathy.. Animals were divided into three groups: Long-Evans-Tokushima-Otsuka rats for normal controls, Otsuka-Long-Evans-Tokushima Fatty (OLETF) rats for the diabetic group, and curcumin-treated (100 mg/kg/day) OLETF rats. We measured body and epididymal fat weights, and examined plasma glucose, adiponectin, and lipid profiles at 45 weeks. To confirm renal damage, we measured albumin-creatinine ratio, superoxide dismutase (SOD), and malondialdehyde (MDA) in urine samples. Glomerular basement membrane thickness and slit pore density were evaluated in the renal cortex tissue of rats. Furthermore, we conducted adenosine monophosphate-activated protein kinase (AMPK) signaling and oxidative stress-related nuclear factor (erythroid-derived 2)-like 2 (Nrf2) signaling to investigate mechanisms of lipotoxicity in kidneys.. Curcumin ameliorated albuminuria, pathophysiologic changes on the glomerulus, urinary MDA, and urinary SOD related with elevated Nrf2 signaling, as well as serum lipid-related index and ectopic lipid accumulation through activation of AMPK signaling.. Collectively, these findings indicate that curcumin exerts renoprotective effects by inhibiting renal lipid accumulation and oxidative stress through AMPK and Nrf2 signaling pathway.

Topics: Albuminuria; Animals; Anti-Inflammatory Agents, Non-Steroidal; Curcumin; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Gene Expression; Inflammation; Kidney; Kidney Glomerulus; Lipid Metabolism; Male; Malondialdehyde; Oxidative Stress; Rats; Rats, Inbred OLETF; Rats, Long-Evans; Superoxide Dismutase

Type 2 diabetes stems from obesity-associated insulin resistance, and in the genetically susceptible, concomitant pancreatic β-cell failure can occur, which further exacerbates hyperglycemia. Recent work by our group and others has shown that the natural polyphenol curcumin attenuates the development of insulin resistance and hyperglycemia in mouse models of hyperinsulinemic or compensated type 2 diabetes. Although several potential downstream molecular targets of curcumin exist, it is now recognized to be a direct inhibitor of proteasome activity. We now show that curcumin also prevents β-cell failure in a mouse model of uncompensated obesity-related insulin resistance (Lepr(db/db) on the Kaliss background).. In this instance, dietary supplementation with curcumin prevented hyperglycemia, increased insulin production and lean body mass, and prolonged lifespan. In addition, we show that short-term in vivo treatment with low dosages of two molecularly distinct proteasome inhibitors celastrol and epoxomicin reverse hyperglycemia in mice with β-cell failure by increasing insulin production and insulin sensitivity.. These studies suggest that proteasome inhibitors may prove useful for patients with diabetes by improving both β-cell function and relieving insulin resistance.

Topics: 3T3-L1 Cells; Animals; Body Composition; Cell Survival; Curcumin; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Dietary Supplements; Glycated Hemoglobin; Homeostasis; Hyperglycemia; Insulin; Insulin Resistance; Insulin Secretion; Insulin-Secreting Cells; Male; Mice; Mice, Inbred C57BL; Obesity; Oligopeptides; Pentacyclic Triterpenes; Polyphenols; Proteasome Inhibitors; Receptors, Leptin; Triterpenes

Obesity and its major co-morbidity, type 2 diabetes, have reached an alarming epidemic prevalence without an effective treatment available. It has been demonstrated that inhibition of SREBP pathway may be a useful strategy to treat obesity with type 2 diabetes. Sterol regulatory element-binding proteins (SREBPs) are major transcription factors regulating the expression of genes involved in biosynthesis of cholesterol, fatty acid and triglyceride. In current study, we identified a small molecule, curcumin, inhibited the SREBP expression in vitro. The inhibition of SREBP by curcumin decreased the biosynthesis of cholesterol and fatty acid. In vivo, curcumin ameliorated HFD-induced body weight gain and fat accumulation in liver or adipose tissues, and improved serum lipid levels and insulin sensitivity in HFD-induced obese mice. Consistently, curcumin regulates SREBPs target genes and metabolism associated genes in liver or adipose tissues, which may directly contribute to the lower lipid level and improvement of insulin resistance. Take together, curcumin, a major active component of Curcuma longa could be a potential leading compound for development of drugs for the prevention of obesity and insulin resistance.

Topics: Adipose Tissue; Animals; Blood Glucose; Cholesterol; Curcumin; Diabetes Mellitus, Type 2; Diet, High-Fat; Down-Regulation; Energy Metabolism; Insulin Resistance; Lipid Metabolism; Male; Mice; Mice, Inbred C57BL; Mice, Obese; Obesity; Sterol Regulatory Element Binding Proteins; Triglycerides; Weight Gain

To observe the effect and mechanism of curcumin derivative B06 on kidney from rats with hyperlipidemia and type 2 diabetes.. Thirty five male SD rats were randomly divided into five groups(n = 7): the normal control group, high-fat group, high-fat + B06-treatd group, diabetic group, diabetic + B06-treated group. After fed with high-fat diet for 4 weeks, the later two groups were in- jected with streptozotocin intraperitoneally to induce type 2 diabetes mellitus. B06-treated groups were given B06 by gavage at a dosage of 0.2 mg/kg . d for 8 weeks. After the treatment, the serum creatinine, blood urea nitrogen and uric acid were detected biochemically, the morphology of kidney was observed with light and transmission electron microscopy, the expression of collagen fibers was observed with Masson staining, the protein expression of collogen IV and fibronectin in kidney were determined by Immunohistochemistry.. It was showed that the levels of the serum creatinine and blood urea nitrogen elevated significantly in diabetic group. In high-fat and diabetic groups, increased glomerular mesangial matrix and collagen fiber and thicken glomerular basal membrane were observed under light microscopy, swelling and fusion of foot process were found under electron microscope; increased green matrix within glomeruli was observed under Masson staining. collogen IV and fibronectin protein expression were significantly enhanced in high-fat group and diabetic group. After B06's intervention, the levels of serum creatinine and blood urea nitrogen were decreased in diabetic groups, the morphological change of kidney was obviously relieved, Collogen IV and fibronectin protein expression reduced.. Curcumin derivative B06 exerts a protective effect on kidney in type 2 diabetic rats, reduced expressions of collogen IV and fibronectin, inhibition of the accumulation of extracellular matrix and glomerular mesangial proliferation, and then prevention of renal fibrosis may be the mechanism.

Topics: Animals; Blood Urea Nitrogen; Collagen Type IV; Creatinine; Curcumin; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Drugs, Chinese Herbal; Fibronectins; Kidney; Kidney Diseases; Male; Rats; Rats, Sprague-Dawley; Streptozocin; Uric Acid

11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) controls the production of active glucocorticoid (GC) and has been proposed as a new target for the treatment of type 2 diabetes. We have previously reported that a natural product, curcumin, exhibited moderate inhibition and selectivity on 11β-HSD1. By analyzing the models of protein, microsome, cells and GCs-induced mice in vitro and in vivo, this study presented a novel curcumin analog, LG13, as a potent selective 11β-HSD1 inhibitor. In vivo, Type 2 diabetic mice were treated with LG13 for 42 days to assess the pharmacological benefits of 11β-HSD1 inhibitor on hepatic glucose metabolism. In vitro studies revealed that LG13 selectively inhibited 11β-HSD1 with IC50 values at nanomolar level and high selectivity over 11β-HSD2. Targeting 11β-HSD1, LG13 could inhibit prednisone-induced adverse changes in mice, but had no effects on dexamethasone-induced ones. Further, the 11β-HSD1 inhibitors also suppressed 11β-HSD1 and GR expression, indicating a possible positive feedback system in the 11β-HSD1/GR cycle. In type 2 diabetic mice induced by high fat diet plus low-dosage STZ injection, oral administration with LG13 for 6 weeks significantly decreased fasting blood glucose, hepatic glucose metabolism, structural disorders, and lipid deposits. LG13 exhibited better pharmacological effects in vivo than insulin sensitizer pioglitazone and potential 11β-HSD1 inhibitor PF-915275. These pharmacological and mechanistic insights on LG13 also provide us novel agents, leading structures, and strategy for the development of 11β-HSD1 inhibitors treating metabolic syndromes.

Topics: 11-beta-Hydroxysteroid Dehydrogenase Type 1; Animals; Blood Glucose; Cell Line; Curcumin; Dexamethasone; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Glucose; Humans; Hypoglycemic Agents; Liver; Male; Mice; Mice, Inbred C57BL; Pioglitazone; Prednisone; Random Allocation; Rats; Thiazolidinediones

Type 2 diabetic mellitus (T2DM) has reached pandemic status and shows no signs of abatement. Diabetic neuropathic pain (DNP) is generally considered to be one of the most common complications of T2DM, which is also recognized as one of the most difficult types of pain to treat. As one kind of peripheral neuropathic pain, DNP manifests typical chronic neuralgia symptoms, including hyperalgesia, allodynia, autotomy, and so on. The injured dorsal root ganglion (DRG) is considered as the first stage of the sensory pathway impairment, whose neurons display increased frequency of action potential generation and increased spontaneous activities. These are mainly due to the changed properties of voltage-gated sodium channels (VGSCs) and the increased sodium currents, especially TTX-R sodium currents. Curcumin, one of the most important phytochemicals from turmeric, has been demonstrated to effectively prevent and/or ameliorate diabetic mellitus and its complications including DNP. The present study demonstrates that the TTX-R sodium currents of small-sized DRG neurons isolated from DNP rats are significantly increased. Such abnormality can be efficaciously ameliorated by curcumin.

Topics: Analgesics; Animals; Curcumin; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Ganglia, Spinal; Insulin Resistance; Male; Neuralgia; Neurons; Pain Threshold; Rats, Sprague-Dawley; Sodium Channels; Tetrodotoxin

Lipotoxicity plays a vital role in development and progression of type 2 diabetes. Prolonged elevation of free fatty acids especially the palmitate leads to pancreatic β-cell dysfunction and apoptosis. Curcumin (diferuloylmethane), a polyphenol from the curry spice turmeric, is considered to be a broadly cytoprotective agent. The present study was designed to determine the protective effect of curcumin on palmitate-induced apoptosis in β-cells and investigate underlying mechanisms. Our results showed that curcumin improved cell viability and enhanced glucose-induced insulin secretory function in MIN6 pancreatic β-cells. Palmitate incubation evoked chromatin condensation, DNA nick end labeling and activation of caspase-3 and -9. Curcumin treatment inhibited palmitate-induced apoptosis, relieved mitochondrial depolarization and up-regulated Bcl-2/Bax ratio. Palmitate induced the generation of reactive oxygen species and inhibited activities of antioxidant enzymes, which could be neutralized by curcumin treatment. Moreover, curcumin could promote rapid phosphorylation of Akt and nuclear exclusion of FoxO1 in MIN6 cells under lipotoxic condition. Phosphatidylinositol 3-kinase and Akt specific inhibitors abolished the anti-lipotoxic effect of curcumin and stimulated FoxO1 nuclear translocation. These findings suggested that curcumin protected MIN6 pancreatic β-Cells against apoptosis through activation of Akt, inhibition of nuclear translocation of FoxO1 and mitochondrial survival pathway.

Topics: Animals; Apoptosis; Cell Line, Tumor; Curcumin; Diabetes Mellitus, Type 2; Forkhead Box Protein O1; Forkhead Transcription Factors; Humans; Insulin-Secreting Cells; Mice; Mitochondria; Palmitates; Phosphatidylinositol 3-Kinases; Phosphorylation; Proto-Oncogene Proteins c-akt; Reactive Oxygen Species; Signal Transduction

Along with the development of economy and society, type 2 diabetic mellitus (T2DM) has become one of the most common diseases at the global level. As one of the complications of T2DM, diabetic neuropathic pain (DNP) stubbornly and chronically affects the health and life of human beings. In the pain field, dorsal root ganglion (DRG) is generally considered as the first stage of the sensory pathway where the hyperexcitability of injured neurons is associated with different kinds of peripheral neuropathic pains. The abnormal electrophysiology is mainly due to the changed properties of voltage-gated sodium channels (VGSCs) and the increased sodium currents (I(Na)). Curcumin is an active ingredient extracted from turmeric and has been demonstrated to ameliorate T2DM and its various complications including DNP effectively. The present study demonstrates that the I(Na) of small-sized DRG neurons are significantly increased with the abnormal electrophysiological characteristics of VGSCs in type 2 diabetic neuropathic pain rats. And these abnormalities can be ameliorated efficaciously by a period of treatment with curcumin.

Topics: Animals; Curcumin; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Ganglia, Spinal; Neuralgia; Neurons; Rats; Sodium; Voltage-Gated Sodium Channels

In the present study, a series of mono-carbonyl analogues of curcumin were designed and synthesized by deleting the reactive beta-diketone moiety, which is responsible for the pharmacokinetic limitation of curcumin. We demonstrated that 4 of 9 curcumin analogues were selective inhibitors of human and rodent 11β-HSD1. The level of this inhibitor was 4-20 times more than that of curcumin. Curcumin analogues weakly inhibited 11β-HSD2, and further analyses revealed that these compounds were highly selective, favoring 11β-HSD1. These 4 curcumin analogues are potential therapeutic agents for type-2 diabetes by targeting 11β-HSD1. The compound 8 displays anti-diabetic properties in diabetic mice induced by streptozocin and high-fat-diet (STZHFD).

Topics: 11-beta-Hydroxysteroid Dehydrogenase Type 1; Animals; Curcumin; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Diet, High-Fat; Dose-Response Relationship, Drug; Enzyme Inhibitors; Humans; Hypoglycemic Agents; Male; Mice; Mice, Inbred C57BL; Mice, Obese; Molecular Structure; Streptozocin; Structure-Activity Relationship

To determine the effect of curcumin on diabetic nephropathy in db/db mice and its possible mechanism.. Ten female db/db mice were randomly divided into 2 groups: one was treated with curcumin at 200 mg/(kg.d) and the other was a placebo group. Five age-matched db/m mice were grouped as the controls. In the curcumin group, curcumin was administered to db/db mice for 18 weeks. At the end of the experiment, the blood glucose and albumin were measured, and the kidney tissue sections were stained with PAS to observe the pathological changes. The expression of collagen IV and FN in the kidney was detected by immunohitochemistry staining. Western blot was used to detect the phosphorylation of signal transducer and activator of transcription 3 (STAT3) and IκB in the kidney.. Compared with db/m mice, the weight and blood glucose of db/db mice were markedly increased, accompanied with heavy proteinuria, glomerulus hypertrophy, mesangial area expansion, thickening of basement membrane and ECM deposition. The phosphorylation of STAT3 was upregulated and the degradation of IκB was increased. Compared with the db/db mice, curcumin significantly decreased the urinary albumin, inhibited the phosphorylation of STAT3 and the degradation of IκB, and reduced the expression of collagen IV and FN in the kidney.. Curcumin can obviously decrease albuminuria and attenuate glomerular sclerosis in diabetic db/db mice by inhibiting phosphorylation of STAT3 and degradation of IκB.

Topics: Albuminuria; Animals; Blood Glucose; Collagen Type IV; Curcumin; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Female; Fibronectins; I-kappa B Proteins; Kidney; Mice; Phosphorylation; Proteinuria; STAT3 Transcription Factor

Nitrosative and oxidative stress play a key role in obesity and diabetes-related mitochondrial dysfunction. The objective was to investigate the effect of curcumin treatment on state 3 and 4 oxygen consumption, nitric oxide (NO) synthesis, ATPase activity and lipid oxidation in mitochondria isolated from liver and kidneys of diabetic db/db mice.. Hyperglycaemia increased oxygen consumption and decreased NO synthesis in liver mitochondria isolated from diabetic mice relative to the control mice. In kidney mitochondria, hyperglycaemia increased state 3 oxygen consumption and thiobarbituric acid-reactive substances (TBARS) levels in diabetic mice relative to control mice. Interestingly, treating db/db mice with curcumin improved or restored these parameters to normal levels; also curcumin increased liver mitochondrial ATPase activity in db/db mice relative to untreated db/db mice.. These findings suggest that hyperglycaemia modifies oxygen consumption rate, NO synthesis and increases TBARS levels in mitochondria from the liver and kidneys of diabetic mice, whereas curcumin may have a protective role against these alterations.

Topics: Adenosine Triphosphatases; Animals; Body Weight; Cell Respiration; Curcumin; Diabetes Mellitus, Type 2; Dietary Supplements; Disease Models, Animal; Genotype; Hyperglycemia; Kidney; Lipid Peroxidation; Liver; Male; Mice; Mitochondria; Mitochondria, Liver; Nitric Oxide; Oxidative Stress; Oxygen Consumption; Selective Breeding

To investigate whether curcumin intake could improve kidney, liver pathological changes in type 2 diabetes (T2DM) rats.. 100 male Wistar rats were randomly divided into two groups: 10 rats in the control group; 90 in the T2DM model rats, the using low-dose treptozotocin (30 mg/kg BW) combined high sugar and high fat diet to induce T2DM model. After the success of the model induction, 39 T2DM rats met the selection criteria, which were randomly divided into 4 groups: T2DM model control group, low-dose curcumin group (50 mg/kg BW), curcumin dose group (150 mg/kg BW) and curcumin high-dose group (250 mg/kg BW), given intervention. After 45 days treatment, rats from each group were randomly selected four for pathological testing and observation of kidney and liver changes.. Compared with the control group, the results showed that blood glucose and lipids in T2DM model group were significantly increased (P < 0.05). Compared to the T2DM control group, curcumin treatment significant improved kidney and liver pathological changes.. Curcumin can improve liver and kidney pathological changes in T2DM rats.

Topics: Animals; Curcumin; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Kidney; Liver; Male; Rats; Rats, Wistar

Hemorrhagic transformation is an important complication of acute ischemic stroke, particularly in diabetic patients receiving thrombolytic treatment with tissue plasminogen activator, the only approved drug for the treatment of acute ischemic stroke. The objective of the present study was to determine the effects of acute manipulation of potential targets for vascular protection [i.e., NF-κB, peroxynitrite, and matrix metalloproteinases (MMPs)] on vascular injury and functional outcome in a diabetic model of cerebral ischemia. Ischemia was induced by middle cerebral artery occlusion in control and type 2 diabetic Goto-Kakizaki rats. Treatment groups received a single dose of the peroxynitrite decomposition catalyst 5,10,15,20-tetrakis(4-sulfonatophenyl)prophyrinato iron (III), the nonspecific NF-κB inhibitor curcumin, or the broad-spectrum MMP inhibitor minocycline at reperfusion. Poststroke infarct volume, edema, hemorrhage, neurological deficits, and MMP-9 activity were evaluated. All acute treatments reduced MMP-9 and hemorrhagic transformation in diabetic groups. In addition, acute curcumin and minocycline therapy reduced edema in these animals. Improved neurological function was observed in varying degrees with treatment, as indicated by beam-walk performance, modified Bederson scores, and grip strength; however, infarct size was similar to untreated diabetic animals. In control animals, all treatments reduced MMP-9 activity, yet bleeding was not improved. Neuroprotection was only conferred by curcumin and minocycline. Uncovering the underlying mechanisms contributing to the success of acute therapy in diabetes will advance tailored stroke therapies.

Topics: Animals; Curcumin; Diabetes Mellitus, Type 2; Edema; Hemorrhage; Infarction, Middle Cerebral Artery; Locomotion; Male; Matrix Metalloproteinase 9; Matrix Metalloproteinase Inhibitors; Metalloporphyrins; Minocycline; Neuroprotective Agents; NF-kappa B; Peroxynitrous Acid; Rats; Rats, Mutant Strains; Rats, Wistar

Curcuma longa rhizome is used extensively in culinary preparations in Far East and South-East Asia. Health benefits of curcuminoids from C. longa as antioxidants, anti-cancer and anti-inflammatory molecules have been well documented. We report here for the first time that Bisdemethoxycurcumin (BDMC) from C. longa, acts as an inhibitor to inactivate human pancreatic α-amylase, a therapeutic target for oral hypoglycemic agents in type-2 diabetes. Bioactivity guided isolation of rhizome isopropanol extract led to the identification by HPLC and NMR of BDMC as a lead small molecule inhibitor of porcine and human pancreatic α-amylase with an IC(50) value of 0.026 and 0.025 mM, respectively. Kinetic analysis revealed that using starch as the substrate, HPA exhibited an uncompetitive mode of inhibition with an apparent K(i) of 3.0 μM. The study gains importance as BDMC could be a good drug candidate in development of new inhibitors of HPA and of functional foods for controlling starch digestion in order to reduce post-prandial hyperglycemia.

Topics: Curcuma; Curcumin; Diabetes Mellitus, Type 2; Diarylheptanoids; Enzyme Inhibitors; Humans; Kinetics; Molecular Weight; Pancreatic alpha-Amylases; Plant Extracts; Rhizome

Curcumin, an active component derived from dietary spice turmeric (Curcuma longa), has been demonstrated antihyperglycemic, antiinflammatory and hypocholesterolemic activities in obesity and diabetes. These effects are associated with decreased level of circulating free fatty acids (FFA), however the mechanism has not yet been elucidated. The flux of FFA and glycerol from adipose tissue to the blood stream primarily depends on the lipolysis of triacylglycerols in the adipocytes. Adipocyte lipolysis is physiologically stimulated by catecholamine hormones. Tumor necrosis factor-α (TNFα) stimulates chronic lipolysis in obesity and type 2 diabetes. In this study, we examined the role of curcumin in inhibiting lipolytic action upon various stimulations in 3T3-L1 adipocytes.. Glycerol release from TNFα or isoproterenol-stimulated 3T3-L1 adipocytes in the absence or presence of curcumin was determined using a colorimetric assay (GPO-Trinder). Western blotting was used to investigate the TNFα-induced phosphorylation of MAPK and perilipin expression. Fatcake and cytosolic fractions were prepared to examine the isoproterenol-stimulated hormone-sensitive lipase translocation.. Treatment with curcumin attenuated TNFα-mediated lipolysis by suppressing phosphorylation of extracellular signal-related kinase 1/2 (ERK1/2) and reversing the downregulation of perilipin protein in TNFα-stimulated adipocytes (p<0.05). The acute lipolytic response to adrenergic stimulation of isoproterenol was also restricted by curcumin (10-20 μM, p<0.05), which was compatible with reduced perilipin phosphorylation(29%, p<0.05) and hormone-sensitive lipase translocation(20%, p<0.05).. This study provides evidence that curcumin acts on adipocytes to suppress the lipolysis response to TNFα and catecholamines. The antilipolytic effect could be a cellular basis for curcumin decreasing plasma FFA levels and improving insulin sensitivity.

Topics: 3T3-L1 Cells; Adipocytes; Animals; Carrier Proteins; Curcuma; Curcumin; Diabetes Mellitus, Type 2; Down-Regulation; Extracellular Signal-Regulated MAP Kinases; Fatty Acids, Nonesterified; Glycerol; Insulin Resistance; Isoproterenol; Lipase; Lipolysis; Mice; Obesity; Perilipin-1; Phosphoproteins; Phosphorylation; Phytotherapy; Plant Extracts; Tumor Necrosis Factor-alpha

Anti-diabetic capacity of Curcuma longa volatile oil in terms of its ability to inhibit glucosidase activities was evaluated. Turmeric volatile oils inhibited glucosidase enzymes more effectively than the reference standard drug acarbose. Drying of rhizomes was found to enhance α-glucosidase (IC₅₀ = 1.32-0.38 μg/ml) and α-amylase (IC₅₀ = 64.7-34.3 μg/ml) inhibitory capacities of volatile oils. Ar-Turmerone, the major volatile component in the rhizome also showed potent α-glucosidase (IC₅₀ = 0.28 μg) and α-amylase (IC₅₀ = 24.5 μg) inhibition.

Topics: Acarbose; alpha-Amylases; alpha-Glucosidases; Curcuma; Diabetes Mellitus, Type 2; Enzyme Inhibitors; Ethnopharmacology; Glycoside Hydrolase Inhibitors; Hot Temperature; Hypoglycemic Agents; India; Ketones; Kinetics; Medicine, Ayurvedic; Oils, Volatile; Rhizome; Sesquiterpenes

Diabetes is a proinflammatory state. We have previously shown increased monocyte proinflammatory cytokines in patients with Type 1 and Type 2 diabetes. High glucose induces proinflammatory cytokines via epigenetic changes. Curcumin, a polyphenol responsible for the yellow color of the spice turmeric, is known to exert potent anti-inflammatory activity in vitro. Recent studies indicate that it may regulate chromatin remodeling by inhibiting histone acetylation. In this study, we aimed to test the effect of curcumin on histone acetylation and proinflammatory cytokine secretion under high-glucose conditions in human monocytes. Human monocytic (THP-1) cells were cultured in presence of mannitol (osmolar control, mannitol) or normoglycemic (NG, 5.5 mmol/L glucose) or hyperglycemic (HG, 25 mmol/L glucose) conditions in absence or presence of curcumin (1.5-12.5 μM) for 72 h. Cytokine level, nuclear factor κB (NF-κB) transactivation, histone deacetylases (HDACs) activity, histone acetylases (HATs) activity were measured by western blots, quantitative reverse transcriptase-polymerase chain reaction, enzyme-linked immunosorbent assay, immunofluorescence staining. HG significantly induced histone acetylation, NF-κB activity and proinflammatory cytokine (interleukin 6, tumor necrosis factor α and MCP-1) release from THP-1 cells. Curcumin suppressed NF-κB binding and cytokine release in THP-1 cells. Also, since p300 histone acetyltransferase is a coactivator of NF-κB, we examined its acetylation. Curcumin treatment also significantly reduced HAT activity, level of p300 and acetylated CBP/p300 gene expression, and induced HDAC2 expression by curcumin. These results indicate that curcumin decreases HG-induced cytokine production in monocytes via epigenetic changes involving NF-κB. In conclusion, curcumin supplementation by reducing vascular inflammation may prevent diabetic complications.

Topics: Anti-Inflammatory Agents; Blotting, Western; Cell Line; Chemokine CCL2; Curcumin; Cytokines; Diabetes Mellitus, Type 2; Enzyme-Linked Immunosorbent Assay; Epigenesis, Genetic; Glucose; Histone Acetyltransferases; Histone Deacetylase 2; Histone Deacetylases; Humans; Interleukin-6; Monocytes; NF-kappa B; Reverse Transcriptase Polymerase Chain Reaction; Transcriptional Activation; Tumor Necrosis Factor-alpha

This study was conducted to investigate the effect of curcumin, obtained from Curcuma longa, in comparison with rosiglitazone on the progression of insulin resistance and type 2 diabetes mellitus (T2DM) and the mechanisms underlying this effect. Insulin resistance and T2DM was induced in male Sprague Dawley rats by high fat diet (HFD) feeding for 60 and for 75 days representing two regimens of the study, protection and treatment. Prophylactic oral administration of curcumin (80 mg/kg), rosiglitazone (1 mg/kg), their combination, or vehicle (in control groups) was started along with HFD feeding in different groups. Treatment is achieved by oral administration of the previously mentioned agents in the last 15 days of HFD feeding after induction of insulin resistance and T2DM in rats. Curcumin showed an anti-hyperglycemic effect and improved insulin sensitivity, and this action may be attributed at least in part to its anti-inflammatory properties as evident by attenuating TNF-α levels in HFD fed rats, and its anti-lipolytic effect as evident by attenuating plasma free fatty acids. The curcumin effects are comparable to those of rosiglitazone, which indicate that they may act similarly. Finally we can say that, curcumin could be a beneficial adjuvant therapy in patients with T2DM.

Topics: Administration, Oral; Analysis of Variance; Animals; Blood Glucose; Body Composition; Curcumin; Diabetes Mellitus, Type 2; Dietary Fats; Fatty Acids, Nonesterified; Glucose Tolerance Test; Hypoglycemic Agents; Insulin; Insulin Resistance; Male; Rats; Rats, Sprague-Dawley; Rosiglitazone; Thiazolidinediones; Triglycerides; Tumor Necrosis Factor-alpha

Spices which show hypoglycaemic, hypolipidaemic and antioxidant activities may have a role in the treatment of diabetes and its complications. The present study aimed to compare the modulatory effects of garlic, ginger, turmeric and their mixture on the metabolic syndrome and oxidative stress in streptozotocin (STZ)-nicotinamide diabetic rats. Diabetes was induced in overnight fasted rats by a single intraperitoneal injection of STZ (65 mg/kg body weight) and nicotinamide (110 mg/kg body weight, 15 min before STZ injection). Diabetic rats orally received either distilled water (as vehicle) or 200 mg/kg body weight of garlic bulb, ginger rhizome or turmeric rhizome powder suspension separately or mixed together (GGT mixture) for twenty-eight consecutive days. The results showed that these spices and their mixture significantly alleviated (80-97 %, P < 0·05-0·001) signs of the metabolic syndrome (hyperglycaemia and dyslipidaemia), the elevation in atherogenic indices and cellular toxicity in STZ-nicotinamide diabetic rats by increasing the production of insulin (26-37 %), enhancing the antioxidant defence system (31-52 %, especially GSH) and decreasing lipid peroxidation (60-97 %). The greatest modulation was seen in diabetic rats that received garlic and the GGT mixture (10-23 % more than that in the ginger and turmeric groups). In conclusion, garlic or the mix including garlic appears to have an impact on each of the measures more effectively than ginger and turmeric and may have a role in alleviating the risks of the metabolic syndrome and cardiovascular complications.

Topics: Animals; Blood Glucose; Cholesterol; Curcuma; Diabetes Mellitus, Type 2; Garlic; Glutathione; Hypoglycemic Agents; Hypolipidemic Agents; Lipids; Lipoproteins; Liver; Male; Oxidative Stress; Phytotherapy; Plant Roots; Random Allocation; Rats; Rats, Wistar; Spices; Zingiber officinale

Seventeen Cree antidiabetic medicinal plants were studied to determine their potential to inhibit cytochrome P450 3A4 (CYP3A4) through mechanism-based inactivation (MBI). The ethanolic extracts of the medicinal plants were studied for their inhibition of CYP3A4 using the substrates testosterone and dibenzylfluorescein (DBF) in high pressure liquid chromatography (HPLC) and microtiter fluorometric assays, respectively. Using testosterone as a substrate, extracts of Alnus incana, Sarracenia purpurea, and Lycopodium clavatum were identified as potent CYP3A4 MBIs, while those from Abies balsamea, Picea mariana, Pinus banksiana, Rhododendron tomentosum, Kalmia angustifolia, and Picea glauca were identified as less potent inactivators. Not unexpectedly, the other substrate, DBF, showed a different profile of inhibition. Only A. balsamea was identified as a CYP3A4 MBI using DBF. Abies balsamea displayed both NADPH- and time-dependence of CYP3A4 inhibition using both substrates. Overall, several of the medicinal plants may markedly deplete CYP3A4 through MBI and, consequently, decrease the metabolism of CYP3A4 substrates including numerous medications used by diabetics.

Topics: Complementary Therapies; Cytochrome P-450 CYP3A; Cytochrome P-450 CYP3A Inhibitors; Diabetes Mellitus, Type 2; Horticultural Therapy; Humans; Hydrastis; Hypoglycemic Agents; Indians, North American; Plant Extracts; Plants, Medicinal; Quebec; Substrate Specificity

The present study evaluates the combined effect of tetrahydrocurcumin and chlorogenic acid on oxidative stress in streptozotocin-nicotinamide-induced diabetic rats. Rats were rendered diabetic by a single intraperitoneal injection (i.p) of streptozotocin (45 mg/kg BW), 15 min after an i.p injection of nicotinamide (110 mg/kg BW). The levels of fasting plasma glucose and insulin were estimated. As an index of oxidative stress, the levels of enzymic antioxidants and lipid peroxidation products were analyzed in liver and kidney. Diabetic rats showed an increase in the levels of fasting plasma glucose, lipid peroxidative products such as thiobarbituric acid reactive substances and lipid hydroperoxides and a decrease in plasma insulin, and enzymic antioxidants viz., superoxide dismutase, catalase, glutathione peroxidase and glutathione-S-transferase. Combined administration of tetrahydrocurcumin (80 mg/kg BW) and chlorogenic acid (5 mg/kg BW) to diabetic rats for 45 days, reversed the biochemical changes to near normal. The above findings were supported by histological observations of the liver and kidney. Together the present study clearly reflects that combined dosage of tetrahydrocurcumin and chlorogenic acid augments enzymic antioxidants with a concomitant decrease in lipid peroxidation and protects against streptozotocin-nicotinamide-induced type 2 diabetes in experimental rats.

Topics: Animals; Antioxidants; Chlorogenic Acid; Curcumin; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Drug Combinations; Kidney; Lipid Peroxidation; Liver; Niacinamide; Oxidative Stress; Oxidoreductases; Protective Agents; Rats; Streptozocin; Treatment Outcome

Adiponectin is positively correlated with insulin sensitivity. Hydroxycinnamic acid derivatives (HADs), observed ubiquitously in plants, have some physiological functions. In this study, we investigated the effect of HADs on serum adiponectin concentrations in mice and on adiponectin secretion of 3T3-L1 adipocytes. In mice, serum adiponectin concentrations were increased by gamma-oryzanol administration. CAPE, curcumin, and trans-ferulic acid markedly enhanced the adiponectin secretion of 3T3-L1 adipocytes, but not gamma-oryzanol. To clarify the effects of gamma-oryzanol in mice or the effects of HADs on the underlying mechanisms of adiponectin secretion, we further investigated the effect of HADs on adiponectin secretion in the NF-kappaB activation state. Although the adiponectin secretion was reduced in the presence of lipopolysaccharide plus TNF-alpha and IFN-gamma, only gamma-oryzanol supported the activity of adiponectin secretion under NF-kappaB activated condition. The results indicate that these HADs might regulate adiponectin secretion by the inhibition of NF-kappaB activation. HADs might be effective for ameliorating type 2 diabetes.

Topics: 3T3-L1 Cells; Adipocytes; Adiponectin; Animals; Caffeic Acids; Coumaric Acids; Curcumin; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Hypolipidemic Agents; Insulin Resistance; Interferon-gamma; Lipopolysaccharides; Male; Mice; Mice, Inbred C57BL; NF-kappa B; Phenylethyl Alcohol; Phenylpropionates; Phytotherapy; Pioglitazone; Plant Extracts; Plant Oils; Rice Bran Oil; Thiazolidinediones; Tumor Necrosis Factor-alpha

Type II diabetes mellitus (T2DM) is often accompanied by non-alcoholic steatohepatitis (NASH) and associated with hypercholesterolemia, that is, increased levels of plasma low-density lipoprotein (LDL) and oxidized LDL (ox-LDL). Approximately one-third of NASH develops hepatic fibrosis. The role of hypercholesterolemia in T2DM and NASH-associated hepatic fibrogenesis remains obscure. We previously reported that the phytochemical curcumin inhibited the activation of hepatic stellate cells (HSCs), the major effector cells during hepatic fibrogenesis, and protected the liver from fibrogenesis in vitro and in vivo. The aims of this study are to evaluate the role of ox-LDL in activation of HSCs, to assess curcumin effects on eliminating the role of ox-LDL, and to further explore the underlying mechanisms. In this report, we observe that ox-LDL alters the expression of genes closely relevant to HSC activation, which is eliminated by curcumin. Curcumin suppresses gene expression of lectin-like oxidized LDL receptor-1 (LOX-1), leading to the blockade of the transport of extracellular ox-LDL into cells. This suppressive effect of curcumin results from the interruption of Wnt signaling and the activation of peroxisome proliferator-activated receptor-gamma (PPARgamma). In conclusion, these results support our initial hypothesis and demonstrate that ox-LDL stimulates HSC activation, which is eliminated by curcumin by suppressing lox-1 expression by interrupting Wnt signaling and stimulating PPARgamma activity. These results provide novel insights into the role of ox-LDL in T2DM and NASH-associated hepatic fibrogenesis and mechanisms by which curcumin suppresses ox-LDL-induced HSC activation, as well as the implication of curcumin in the treatment of T2DM and NASH-associated hepatic fibrosis.

Topics: Animals; Blotting, Western; Coloring Agents; Curcumin; Diabetes Mellitus, Type 2; Gene Expression Regulation; Gene Silencing; Hepatic Stellate Cells; Hypercholesterolemia; Lipoproteins, LDL; Liver Cirrhosis; Male; Mutagenesis, Site-Directed; PPAR gamma; Rats; Rats, Sprague-Dawley; Receptors, Oxidized LDL

Obesity is a major risk factor for the development of type 2 diabetes, and both conditions are now recognized to possess significant inflammatory components underlying their pathophysiologies. We tested the hypothesis that the plant polyphenolic compound curcumin, which is known to exert potent antiinflammatory and antioxidant effects, would ameliorate diabetes and inflammation in murine models of insulin-resistant obesity. We found that dietary curcumin admixture ameliorated diabetes in high-fat diet-induced obese and leptin-deficient ob/ob male C57BL/6J mice as determined by glucose and insulin tolerance testing and hemoglobin A1c percentages. Curcumin treatment also significantly reduced macrophage infiltration of white adipose tissue, increased adipose tissue adiponectin production, and decreased hepatic nuclear factor-kappaB activity, hepatomegaly, and markers of hepatic inflammation. We therefore conclude that orally ingested curcumin reverses many of the inflammatory and metabolic derangements associated with obesity and improves glycemic control in mouse models of type 2 diabetes. This or related compounds warrant further investigation as novel adjunctive therapies for type 2 diabetes in man.

Topics: Adiponectin; Adipose Tissue, White; Animals; Anti-Inflammatory Agents, Non-Steroidal; Antioxidants; Blood Glucose; Curcumin; Diabetes Mellitus, Type 2; Dietary Supplements; Disease Models, Animal; Gene Expression; Immunohistochemistry; Inflammation; Interleukin-6; Liver; Male; Mice; Mice, Inbred C57BL; Mice, Obese; NF-kappa B; Obesity; Reverse Transcriptase Polymerase Chain Reaction; Tumor Necrosis Factor-alpha

Curcuma longa (Zingiberaceae) has been used traditionally as antidiabetic and has been proven scientifically to possess high antioxidant activity and anticancer properties. The active components of Curcuma longa such as curcumin and tetrahydrocurcumin (THC), a major colourless metabolite of curcumin also possesses antidiabetic, antiinflammatory and antioxidant activity. In the present study the effect of THC and curcumin on erythrocyte membrane bound enzymes and antioxidants activity in streptozotocin (STZ) and nicotinamide induced type 2 diabetic model was investigated. Oral administration of THC at 80 mg/kg body weight to diabetic rats for 45 days. The effect of THC and curcumin on glucose, insulin, haemoglobin, glycosylated haemoglobin, thiobarbituric acid reactive substances (TBARS), superoxide dismutase (SOD), catalase (CAT), glutathione peroxide (Gpx), glutathione-S-transferase (GST), reduced glutathione (GSH) and membrane bound enzymes were studied. The effect of THC was compared with curcumin. The levels of blood glucose, glycosylated haemoglobin, erythrocyte TBARS, were increased significantly whereas the level of plasma insulin and haemoglobin, erythrocyte antioxidants (SOD, CAT, GPx, GST and GSH), membrane bound total ATPase, Na(+)/K(+)-ATPase, Ca(2+)-ATPase, Mg(2+)-ATPase were decreased significantly in diabetic rats. Administration of THC and curcumin to diabetic rats showed decreased level of blood glucose, glycosylated haemoglobin and erythrocyte TBARS. In addition the levels of plasma insulin, haemoglobin, erythrocyte antioxidants and the activities of membrane bound enzymes also were increased in THC and curcumin treated diabetic rats. These biochemical observations were supplemented by histopathological examination of pancreas section. The present study indicates that the THC possesses a significant beneficial effect on erythrocyte membrane bound enzymes and antioxidants defense in addition to its antidiabetic effect.

Topics: Adenosine Triphosphatases; Animals; Blood Glucose; Catalase; Curcumin; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Erythrocyte Membrane; Erythrocytes; Glutathione; Glutathione Peroxidase; Glutathione Transferase; Glycosylation; Hemoglobins; Hypoglycemic Agents; Insulin; Male; Pancreas; Rats; Rats, Wistar; Superoxide Dismutase; Thiobarbituric Acid Reactive Substances

Curcumin is the most active component of turmeric. It is believed that curcumin is a potent antioxidant and anti-inflammatory agent. Tetrahydrocurcumin is one of the major metabolites of curcumin that exhibits many of the same physiologic and pharmacological activities as curcumin and in some systems may exert greater antioxidant activity than curcumin. Oral administration of tetrahydrocurcumin at 80 mg/kg body weight to diabetic rats for 45 days resulted in a significant reduction in blood glucose and significant increase in plasma insulin levels. In addition, the diabetic rats had decreased levels of plasma total protein, albumin, globulin and albumin/globulin ratio as compared to control rats. After treatment with tetrahydrocurcumin and curcumin total protein, albumin, globulin and albumin/globulin ratio were brought back to near normal. The activities of hepatic and renal markers were significantly elevated in diabetic rats as compared to control rats, and treatment with tetrahydrocurcumin and curcumin has reversed these parameters to near normal levels. In diabetic rats, the decreased levels of urea, uric acid and creatinine with increased levels of albumin and urine volume was observed, and treatment with tetrahydrocurcumin and curcumin reversed these parameters to near normal. Tetrahydrocurcumin appeared to have a better protective effect when compared to curcumin.

Topics: Animals; Antioxidants; Biomarkers; Chemoprevention; Curcumin; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Kidney; Liver; Male; Niacinamide; Rats; Rats, Wistar; Streptozocin

Hyperlipidemia is an associated complication of diabetes mellitus. In the present study, we investigated the effect of tetrahydrocurcumin (THC), one of the active metabolites of curcumin on lipid profile in streptozotocin (STZ)-nicotinamide-induced diabetic rats. THC 80 mg/kg body weight was orally administered to diabetic rats for 45 days, resulting in a significant reduction in blood glucose and a significant increase in plasma insulin in diabetic rats, which proved that THC possess an antidiabetic effect. THC also caused a significant reduction serum and liver cholesterol, triglycerides, free fatty acids, phospholipids, HMG CoA reductase activity, very low-density lipoprotein (VLDL) and low-density lipoprotein (LDL) cholesterol levels. The decreased serum high-density lipoprotein (HDL) cholesterol in diabetic rats was also reversed toward normalization after the treatment. These biochemical observations were supplemented by histopathological examination of liver section. The effect was compared with curcumin (80 mg/kg body weight). The results showed that THC had antihyperlipidemic action in control and experimental diabetic rats. The antidiabetic and antihyperlipidemic effects of THC are more potent than those of curcumin at the same dose.

Topics: Animals; Blood Glucose; Cholesterol, HDL; Cholesterol, LDL; Curcumin; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Hydroxymethylglutaryl CoA Reductases; Hypolipidemic Agents; Lipid Metabolism; Liver; Male; Rats; Rats, Wistar; Streptozocin

Changes in the structural and functional properties of collagen caused by advanced glycation might be of importance for the etiology of late-stage complications in diabetics. Curcumin is the most active component of turmeric. It is believed that curcumin is a potent antioxidant and anti-inflammatory agent. Tetrahydrocurcumin (THC) is one of the major metabolites of curcumin, exhibiting many of the same physiological and pharmacological activities of curcumin and in some systems may exert greater antioxidant activity than curcumin. In diabetic rats, hydroxyproline and collagen content as well as its degree of cross-linking were increased, as shown by increased extent of glycation, collagen-linked fluorescence, neutral salt collagen, and decreased acid and pepsin solubility. Administration of THC for 45 days to diabetic rats significantly reduced the accumulation and cross-linking of collagen. The effects of THC were comparable with those of curcumin. In conclusion, administration of THC had a positive influence on the content of collagen and its properties in streptozotocin- and nicotinamide-induced diabetic rats. THC was found to be more effective than curcumin.

Topics: Animals; Collagen; Curcumin; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Hydroxyproline; Male; Niacinamide; Rats; Rats, Wistar; Streptozocin; Tail; Tendons

Turmeric, the rhizome of Curcuma longa L., has a wide range of effects on human health. Turmeric oleoresin, an extract of turmeric, is often used for flavoring and coloring. Curcuminoids and turmeric essential oil are both contained in turmeric oleoresin, and both of these fractions have hypoglycemic effects. In the present study, we comprehensively assessed the effect of turmeric oleoresin on hepatic gene expression in obese diabetic KK-Ay mice using DNA microarray analysis and quantitative real-time polymerase chain reaction (PCR). Female KK-Ay mice aged 6 weeks (n = 6/group) were fed a high-fat diet containing turmeric oleoresin, curcuminoids, and essential oil for 5 weeks. The same diet without any of these fractions was used as a control diet. Ingestion of turmeric oleoresin and essential oil inhibited the development of increased blood glucose and abdominal fat mass, while curcuminoids only inhibited the increase in blood glucose. DNA microarray analysis indicated that turmeric oleoresin ingestion up-regulated the expression of genes related to glycolysis, beta-oxidation, and cholesterol metabolism in the liver of KK-Ay mice, while expression of gluconeogenesis-related genes was down-regulated. Real-time PCR analysis was conducted to assess the contribution of the curcuminoids and essential oil in turmeric oleoresin to the changes in expression of representative genes selected by DNA microarray analysis. This analysis suggested that curcuminoids regulated turmeric oleoresin ingestion-induced expression of glycolysis-related genes and also that curcuminoids and turmeric essential oil acted synergistically to regulate the peroxisomal beta-oxidation-related gene expression induced by turmeric oleoresin ingestion. These changes in gene expression were considered to be the mechanism by which the turmeric oleoresin affected the control of both blood glucose levels and abdominal adipose tissue masses. All of these results suggest that the use of whole turmeric oleoresin is more effective than the use of either curcuminoids or the essential oil alone.

Topics: Animals; Blood Glucose; Curcuma; Diabetes Mellitus, Type 2; Female; Hypoglycemic Agents; Lipid Metabolism; Mice; Mice, Obese; Oligonucleotide Array Sequence Analysis; Phytotherapy; Plant Extracts; Plant Oils; Rhizome

Turmeric, the rhizome of Curcuma longa L., has a wide range of effects on human health. The chemistry includes curcuminoids and sesquiterpenoids as components, which are known to have antioxidative, anticarcinogenic, and antiinflammatory activities. In this study, we investigated the effects of three turmeric extracts on blood glucose levels in type 2 diabetic KK-A(y) mice (6 weeks old, n = 5/group). These turmeric extracts were obtained by ethanol extraction (E-ext) to yield both curcuminoids and sesquiterpenoids, hexane extraction (H-ext) to yield sesquiterpenoids, and ethanol extraction from hexane-extraction residue (HE-ext) to yield curcuminoids. The control group was fed a basal diet, while the other groups were fed a diet containing 0.1 or 0.5 g of H-ext or HE-ext/100 g of diet or 0.2 or 1.0 g of E-ext/100 g of diet for 4 weeks. Although blood glucose levels in the control group significantly increased (P < 0.01) after 4 weeks, feeding of 0.2 or 1.0 g of E-ext, 0.5 g of H-ext, and 0.5 g of HE-ext/100 g of diet suppressed the significant increase in blood glucose levels. Furthermore, E-ext stimulated human adipocyte differentiation, and these turmeric extracts had human peroxisome proliferator-activated receptor-gamma (PPAR-gamma) ligand-binding activity in a GAL4-PPAR-gamma chimera assay. Also, curcumin, demethoxycurcumin, bisdemethoxycurcumin, and ar-turmerone had PPAR-gamma ligand-binding activity. These results indicate that both curcuminoids and sesquiterpenoids in turmeric exhibit hypoglycemic effects via PPAR-gamma activation as one of the mechanisms, and suggest that E-ext including curcuminoids and sesquiterpenoids has the additive or synergistic effects of both components.

Topics: Adipocytes; Animals; Blood Glucose; Cell Differentiation; Curcuma; Curcumin; Diabetes Mellitus, Type 2; Ethanol; Humans; Hypoglycemic Agents; Mice; Plant Extracts; PPAR gamma; Sesquiterpenes

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

Lectin-like oxidized LDL receptor-1 (LOX-1) is a newly identified receptor for oxidized LDL that is expressed by vascular cells. LOX-1 is upregulated in aortas of diabetic rats and thus may contribute to the pathogenesis of human diabetic atherosclerosis. In this study, we examined the regulation of human monocyte-derived macrophage (MDM) LOX-1 expression by high glucose and the role of LOX-1 in glucose-induced foam cell formation. Incubation of human MDMs with glucose (5.6 to 30 mmol/L) enhanced, in a dose- and time-dependent manner, LOX-1 gene and protein expression. Induction of LOX-1 gene expression by high glucose was abolished by antioxidants, protein kinase C (PKC), mitogen-activated protein kinases (MAPKs), nuclear factor-kappaB (NF-kappaB), and activated protein-1 (AP-1) inhibitors. In human MDMs cultured with high glucose, increased expression of PKCbeta2 and enhanced phosphorylation of extracellular signal-regulated protein kinase 1/2 was observed. Activation of these kinases was inhibited by the antioxidant N-acetyl-L-cysteine (NAC) and by the PKCbeta inhibitor LY379196. High glucose also enhanced the binding of nuclear proteins extracted from human MDMs to the NF-kappaB and AP-1 regulatory elements of the LOX-1 gene promoter. This effect was abrogated by NAC and PKC/MAPK inhibitors. Finally, high glucose induced human macrophage-derived foam cell formation through a LOX-1-dependent pathway. Overall, these results demonstrate that high glucose concentrations enhance LOX-1 expression in human MDMs and that this effect is associated with foam cell formation. Pilot data showing that MDMs of patients with type 2 diabetes overexpress LOX-1 support the relevance of this work to human diabetic atherosclerosis.

Topics: Acetylcysteine; Adult; Aged; Anti-Infective Agents; Antioxidants; Arteriosclerosis; Cells, Cultured; Curcumin; Diabetes Mellitus, Type 2; Enzyme Inhibitors; Female; Flavonoids; Foam Cells; Gene Expression Regulation; Glucose; Glycation End Products, Advanced; Humans; Hyperglycemia; Macrophages; Male; MAP Kinase Signaling System; Mesylates; Middle Aged; Mitogen-Activated Protein Kinase 1; Mitogen-Activated Protein Kinase 3; Mitogen-Activated Protein Kinases; NF-kappa B; Nitriles; Phosphorylation; Protein Kinase C; Protein Kinase C beta; Protein Processing, Post-Translational; Pyrroles; Receptors, LDL; RNA, Messenger; Signal Transduction; Sulfones; Transcription Factor AP-1; Tumor Necrosis Factor-alpha