curcumin and Diabetes-Mellitus

Obesity, as an unfavorable consequence of our modern lifestyle, can promote the emergence of other disorders, like diabetes and cardiovascular disease, that negatively impact quality of life. Therefore, prevention and treatment of obesity and its related comorbidities are critical. Lifestyle modification is the first and most important step but, in practical terms, presents a major challenge to many patients. So, the development of new strategies and therapies is critical for these patients. Although herbal bioactive compounds have recently gained attention for their ability to prevent and treat conditions related to obesity, no ideal pharmacological treatment has been found to treat obesity. Curcumin, one of the compounds extracted from turmeric, is a well-studied active herbal extract; however, its poor bioavailability and solubility in water, instability against temperature, light and pH fluctuations and rapid excretion limit its therapeutic application. Curcumin modification can, however, provide novel analogues with better performance and fewer disadvantages in comparison to the original structure. In the past few years, the positive effects of synthetic analogues of curcumin for the treatment of obesity, diabetes and cardiovascular disorders have been reported. In this review, we evaluate the strengths and weaknesses of the reported artificial derivatives and assess their practicality as therapeutic agents.

Topics: Cardiovascular Diseases; Curcumin; Diabetes Mellitus; Humans; Obesity; Quality of Life

Diabetes mellitus is a chronic disease, typified by hyperglycemia resulting from failures in complex multifactorial metabolic functions, that requires life-long medication. Prolonged uncontrolled hyperglycemia leads to micro- and macro-vascular complications. Although antidiabetic drugs are prescribed as the first-line treatment, many of them lose efficacy over time or have severe side effects. There is a lack of in-depth study on the patents filed concerning the use of natural compounds to manage diabetes. Thus, this patent analysis provides a comprehensive report on the antidiabetic therapeutic activity of 6 phytocompounds when taken alone or in combinations. Four patent databases were searched, and 17,649 patents filed between 2001 and 2021 were retrieved. Of these, 139 patents for antidiabetic therapeutic aids that included berberine, curcumin, gingerol, gymnemic acid, gymnemagenin and mangiferin were analyzed. The results showed that these compounds alone or in combinations, targeting acetyl-coenzyme A carboxylase 2, serine/threonine protein kinase, α-amylase, α-glucosidase, lipooxygenase, phosphorylase, peroxisome proliferator-activated receptor-γ (PPARγ), protein tyrosine phosphatase 1B, PPARγ co-activator-1α, phosphoinositide 3-kinase and protein phosphatase 1 regulatory subunit 3C, could regulate glucose metabolism which are validated by pharmacological rationale. Synergism, or combination therapy, including different phytocompounds and plant extracts, has been studied extensively and found effective, whereas the efficacy of commercial drugs in combination with phytocompounds has not been studied in detail. Curcumin, gymnemic acid and mangiferin were found to be effective against diabetes-related complications. Please cite this article as: DasNandy A, Virge R, Hegde HV, Chattopadhyay D. A review of patent literature on the regulation of glucose metabolism by six phytocompounds in the management of diabetes mellitus and its complications. J Integr Med. 2023; 21(3): 226-235.

Topics: Curcumin; Diabetes Mellitus; Glucose; Humans; Hyperglycemia; Hypoglycemic Agents; Phosphatidylinositol 3-Kinases; PPAR gamma

Flavonoids are important bioactive phenolic compounds abundant in plants and exhibit different therapeutic potentials. A wound is a significant problem in diabetic individuals. A hyperglycaemic environment alters the normal wound-healing process and increases the risk of microbial infection, leading to hospitalization, morbidity, and amputation. Flavonoids are an important class of phytochemicals with excellent antioxidant, anti-inflammatory, antimicrobial, antidiabetic, antitumor, and wound healing property. Quercetin, hesperidin, curcumin, kaempferol, apigenin, luteolin, morin, etc. have shown their wound healing potential. Flavonoids effectively exhibit antimicrobial activity, scavenge reactive oxygen species, augment endogenous antioxidants, reduce the expression and synthesis of inflammatory cytokines (i.e. IL-1β, IL-6, TNF-α, NF-κB), inhibit inflammatory enzymes, enhance anti-inflammatory cytokine (IL-10), enhance insulin section, reduce insulin resistance, and control blood glucose level. Several flavonoids like hesperidin, curcumin, quercetin, rutin, naringin, and luteolin have shown their potential in managing diabetic wounds. Natural products that maintain glucose haemostatic, exert anti-inflammatory activity, suppress/inhibit microbial growth, modulate cytokines, inhibit matrix metalloproteinase (MMP), stimulate angiogenesis and extracellular matrix, and modulate growth factor can be considered as a potential therapeutic lead to treat diabetic wound. Flavonoids were found to play a positive role in management of diabetic wounds by regulating MMP-2, MMP-8, MMP-9, MMP-13, Ras/Raf/ MEK/ERK, PI3K/Akt, and nitric oxide pathways. Therefore, it can be assumed that flavonoids could be potential therapeutics to prevent devastating effects of diabetic wounds. This paper focused on the potential role of flavonoids in managing diabetic wounds and discussed their possible mechanism of action.

Topics: Anti-Inflammatory Agents; Curcumin; Cytokines; Diabetes Mellitus; Flavonoids; Hesperidin; Humans; Luteolin; Phosphatidylinositol 3-Kinases; Quercetin

Diabetes is predicted to affect 700 million people by the year 2045. Despite the potential benefits for diabetics, curcumin's low bioavailability significantly reduces its utility. However, newer formulation methods of decreasing particle size, such as through nanotechnological advances, may improve curcumin's bioavailability and cell-absorption properties. Various curcumin nanoformulations such as nanofibers, nanoparticles-like nanostructured lipid carriers (NLCs), Solid Self-Nanoemulsifying Drug Delivery Systems (S-SNEDDS) and nanohydrogels have been evaluated. These studies reported increased bioavailability of nanoformulated curcumin compared to free curcumin. Here, we provide a detailed review of the antidiabetic effects of nanocurcumin compounds and subsequent effects on diabetic complications. Overall, various nanocurcumin formulations highly increase curcumin water-solubility and bioavailability and these safe formulations can positively affect managing some diabetes-related manifestations and complications. Moreover, nanocurcumin efficacy in various diabetes complications is discussed. These complications included inflammation, neuropathy, depression, anxiety, keratopathy, cataract, cardiomyopathy, myocardial infarction (MI), nephropathy, erectile dysfunction and diabetic wound. Moreover, several nanocurcumin formulations improved wound healing in the diabetic. However, few studies have been performed in humans, and most results have been reported from cellular and animal studies. Therefore, more human studies are needed to prove the antidiabetic effects of nanocurcumin.

Topics: Animals; Biological Availability; Curcumin; Diabetes Mellitus; Drug Delivery Systems; Humans; Hypoglycemic Agents; Male; Nanoparticles; Particle Size

Diabetic retinopathy (DR) is a form of retinal microangiopathy that occurs as a result of long-term Diabetes mellitus (DM). Patients with Diabetes mellitus typically suffer from DR as a progression of the disease that may be due to initiation and dysregulation of pathways like the polyol, hexosamine, the AGE/RAGE, and the PKC pathway, which all have negative impacts on eye health and vision. In this review, various databases, including PubMed, Google Scholar, Web of Science, and Science Direct, were scoured for data relevant to the aforementioned title. The three most common therapies for DR today are retinal photocoagulation, anti-vascular endothelial growth factor (VEGF) therapy, and vitrectomy, however, there are a number of drawbacks and limits to these methods. So, it is of critical importance and profound interest to discover treatments that may successfully address the pathogenesis of DR. Curcumin and β-glucogallin are the two potent compounds of natural origin that are already being used in various nutraceutical formulations for several ailments. They have been shown potent antiapoptotic, anti-inflammatory, antioxidant, anticancer, and pro-vascular function benefits in animal experiments. Their parent plant species have been used for generations by practitioners of traditional herbal medicine for the treatment and prevention of various eye ailments. In this review, we will discuss about pathophysiology of Diabetic retinopathy and the therapeutic potentials of curcumin and β-glucogallin one of the principal compounds from Curcuma longa and Emblica officinalis in Diabetic retinopathy.

Topics: Animals; Curcumin; Diabetes Mellitus; Diabetic Retinopathy; Humans; Hydrolyzable Tannins; Retina

The pathobiology of diabetes and associated complications has been widely researched in various countries, but effective prevention and treatment methods are still insufficient. Diabetes is a metabolic disorder of carbohydrates, fats, and proteins caused by an absence of insulin or insulin resistance, which mediates an increase of oxidative stress, release of inflammatory factors, and macro- or micro-circulation dysfunctions, ultimately developing into diverse complications.. In the last decade through pathogenesis research, epigenetics has been found to affect metabolic diseases. Particularly, DNA methylation, histone acetylation, and miRNAs promote or inhibit diabetes and complications by regulating the expression of related factors. Curcumin has a wide range of beneficial pharmacological activities, including anti-inflammatory, anti-oxidation, anticancer, anti-diabetes, anti-rheumatism, and increased immunity. Key Messages: In this review, we discuss the effects of curcumin and analogs on diabetes and associated complications through epigenetics, and we summarize the preclinical and clinical researches for curcumin and its analogs in terms of management of diabetes and associated complications, which may provide an insight into the development of targeted therapy of endocrine diseases.

Topics: Acetylation; Animals; Curcumin; Diabetes Complications; Diabetes Mellitus; DNA Methylation; Epigenesis, Genetic; Humans; MicroRNAs

Diabetes is a metabolic disease with multifactorial causes which requires lifelong drug therapy as well as lifestyle changes. There is now growing scientific evidence to support the effectiveness of the use of herbal supplements in the prevention and control of diabetes. Curcumin is one of the most studied bioactive components of traditional medicine, but its physicochemical characteristics are represented by low solubility, poor absorption, and low efficacy. Nanotechnology-based pharmaceutical formulations can help overcome the problems of reduced bioavailability of curcumin and increase its antidiabetic effects. The objectives of this review were to review the effects of nanocurcumin on DM and to search for databases such as PubMed/MEDLINE and ScienceDirect. The results showed that the antidiabetic activity of nanocurcumin is due to complex pharmacological mechanisms by reducing the characteristic hyperglycemia of DM. In light of these results, nanocurcumin may be considered as potential agent in the pharmacotherapeutic management of patients with diabetes.

Topics: Biological Availability; Curcumin; Diabetes Mellitus; Humans; Nanotechnology

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

Diabetic nephropathy (DN) is the leading cause of end-stage renal disease and is an enormous burden on both patients and society. There is an urgent need for effective alternative therapeutic strategies for the treatment of DN, as medical treatment is currently limited. The anti-inflammatory, antioxidative, anti-apoptotic, and anti-fibrosis properties of curcumin, a polyphenol curcuminoid, have been demonstrated in research on diabetic nephropathy. The clinical and preclinical trials and mechanisms by which curcumin affects DN have been discussed in this review. A deeper understanding of the pharmacological effects of curcumin on diabetic nephropathy may provide new therapies to improve the development and occurrence of diabetic nephropathy.

Topics: Anti-Inflammatory Agents; Curcumin; Diabetes Mellitus; Diabetic Nephropathies; Diarylheptanoids; Humans; Polyphenols

There is growing interest in the health benefits of natural plant pigments such as anthocyanins and curcumin. In this review, we introduce how these pigments can contribute to the prevention of diabetes and obesity by stimulating glucagon-like peptide-1 (GLP-1) secretion or inducing beige adipocyte formation. Of the anthocyanins, delphinidin 3-rutinoside (D3R) was shown to increase GLP-1 secretion. Pre-administered D3R-rich blackcurrant extract (BCE) significantly ameliorated glucose tolerance after intraperitoneal glucose injection in rats by stimulating the secretion of GLP-1 and subsequently inducing insulin secretion. D3R did not break down significantly in the gastrointestinal tract for at least 45-60 min after BCE administration. An increase in endogenous GLP-1 secretion induced by food-derived factors may help to reduce the dosages of diabetic medicines and prevent diabetes. Curcumin has various biological functions, including anti-obesity and anti-diabetic properties. However, high doses of curcumin have been administered in most animal and human trials to date, due mainly to the poor solubility of native curcumin in water and its low oral bioavailability. We demonstrated that a highly dispersible and bioavailable curcumin formulation (HC), but not native curcumin, induces the formation of beige adipocytes. Furthermore, co-administration of HC and artepillin C (a characteristic constituent of Brazilian propolis) at lower doses significantly induces beige adipocyte formation in mice, but administration of the same dose of HC or artepillin C alone does not. Our studies demonstrate that curcumin formulations or the co-administration of curcumin with other food-derived factors provide effects that native curcumin alone does not.

Topics: Adipocytes, Beige; Animals; Anthocyanins; Curcumin; Diabetes Mellitus; Glucagon-Like Peptide 1; Glucose; Humans; Mice; Obesity; Rats; Ribes

The current study aimed to identify which natural products and which research directions are related to the major contributors to academic journals for diabetes therapy. Bibliometric data were extracted from the Web of Science online database using the search string TOPIC = (''natural product*' OR ''natural compound*' OR ''natural molecule*' OR 'phytochemical*' OR ''secondary metabolite*') AND TS = ('diabet*') and analysed by a bibliometric software, VOSviewer. The search yielded 3694 publications, which were collectively cited 80,791 times, with an H-index of 117 and 21.9 citations per publication on average. The top-contributing countries were India, the USA, China, South Korea and Brazil. Curcumin, flavanone, resveratrol, carotenoid, polyphenols, flavonol, flavone and berberine were the most frequently cited natural products or compound classes. Our results provide a brief overview of the major directions of natural product research in diabetes up to now and hint on promising avenues for future research.

Topics: Bibliometrics; Biological Products; Curcumin; Diabetes Mellitus; Humans; Software

Diabetes mellitus (DM) is an ensemble of metabolic conditions that have reached pandemic proportions worldwide. Pathology's multifactorial nature makes patient management, including lifelong drug therapy and lifestyle modification, extremely challenging. Currently, there is growing evidence about the effectiveness of using herbal supplements in preventing and controlling DM. Curcumin is a bioactive component found

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Curcumin; Diabetes Mellitus; Humans

Autophagy is a highly conserved cellular degradation process involving lysosomal degradation for the turnover of proteins, protein complexes, and organelles. Defects in autophagy produces impaired intercellular communication and have subsequently been shown to be associated with pathological conditions, including neurodegenerative diseases. Curcumin is a polyphenol found in the rhizome of Curcuma longa, which has been shown to exert health benefits, such as antimicrobial, antioxidant, anti-inflammatory, and anticancer effects. There is increasing evidence in the literature revealing that autophagy modulation may provide neuroprotective effects. In light of this, our current review aims to address recent advances in the neuroprotective role of curcumin-induced autophagy modulation, specifically with a particular focus on its effects in Alexander disease, Alzheimer's disease, ischemia stroke, traumatic brain injury, and Parkinson's disease.

Topics: Autophagy; Biological Availability; Brain Injuries, Traumatic; Brain Neoplasms; Curcumin; Diabetes Mellitus; Humans; Neurodegenerative Diseases; Neuroprotective Agents

Studies regarding the uses and biological benefits curcumin have long been paid worldwide attention. Curcumin is a polyphenol found in the turmeric spice, which is derived from the rhizomes of Curcuma longa. Curcumin is a major constituent of the traditional Indian holistic system, Ayurveda, and it is well-known in treating diverse ailments. The aim of this study is to conduct an overview that introduces the traditional uses and therapeutic effects of this valuable phytochemical with more focus on the antitumor results. This review was conducted based on published articles on PubMed, Medline, and Web of Science databases. In this study, the search strategy identified 103 references. Curcumin is found to possess many functions in recent years. It is commonly used for its antioxidant, antimicrobial, anti-inflammatory, antitumor, anti-diabetic, hypolipidemic, hepatoprotective, and neuroprotective effects. Curcumin has been greatly reported to prevent many diseases through modulating several signaling pathways, and the molecular bases of its anti-tumor bioactivities are imputed to the antiproliferative, anti-inflammatory, pro-apoptotic, anti-angiogenesis and anti-metastasis effects. The antitoxic potential of curcumin against various toxin like Aflatoxin B1 is reported. Although curcumin is a safe and promising phytochemical, it suffers from bioavailability problems that limit its therapeutic efficacy. Thus, various promising strategies allowed for the achievement of multiple and effective varieties of curcumin formulations, such as adjuvants, nanoparticles, liposome, micelle and phospholipid complexes, metal complexes, derivatives, and analogues. In conclusion, curcumin is widely used for myriad therapeutic purposes that trigger its significant value. This short review aims to highlight the known biological activities of curcumin and provide evidence for its antitumor effects.

Topics: Animals; Antineoplastic Agents; Antioxidants; Apoptosis; Curcuma; Curcumin; Diabetes Mellitus; Herbal Medicine; Hypoglycemic Agents; Neoplasms

It is undeniable that diabetes may cause several health complications for the population. Many of these complications are associated with poor glycemic control. Due to this, strategies to handle this problem are of great clinical importance and may contribute to reducing the various complications from diabetes.. The aim of this study was to compare the effectiveness of the passion fruit peel flour versus turmeric flour on glycemic control.. This is a systematic review and meta-analysis following the PRISMA protocol. The following inclusion criteria were applied: (1) Case-control studies, cohort studies, and clinical trials, due to the improved statistical analysis and, in restrict cases, cross-sectional studies; (2) Articles published in any language. The databases used for the search were PubMed, Scopus, Web of Science, Cochrane, and LILACS. A bias analysis and a meta-analyses were undertaken using R Studio (version 3.3.1) using effect- size models.. A total of 565 studies were identified from which 11 met the inclusion and exclusion criteria. Through isolated analysis, the effectiveness of turmeric flour on glycemic control was in the order of 0.73 CI (Confidence Interval) (from 0.68 to 0.79) and the effectiveness of passion fruit peel flour was 0.32 CI (0.23 to 0.45). The joint analysis resulted in 0.59 CI (0.52 to 0.68). The assessment of blood glucose was by glycated hemoglobin levels. All values were significant at a p < 0.05 level.. Both interventions showed significant effects on glycemic control.

Topics: Blood Glucose; Curcuma; Diabetes Mellitus; Glycated Hemoglobin; Humans; Passiflora; Phytotherapy; Plant Preparations; Plant Structures

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

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

Recent controversy regarding the therapeutic potential of curcumin indicates the challenges to research in this field. Here, we highlight the investigations of curcumin and other plant-derived polyphenols that demonstrate their application to metabolic diseases, in particular, obesity and diabetes. Thus, a number of preclinical and clinical investigations have shown the beneficial effect of curcumin (and other dietary polyphenols) in attenuating body weight gain, improving insulin sensitivity, and preventing diabetes development in rodent models and prediabetic subjects. Other intervention studies with dietary polyphenols have also found improvements in insulin resistance. Recent studies suggest that the metabolic effects of curcumin/polyphenols are linked to changes in the gut microbiota. Thus, research into curcumin continues to provide novel insights into metabolic regulation that may ultimately translate into effective therapy.

Topics: Animals; Curcumin; Diabetes Mellitus; Diet; Energy Metabolism; Humans; Insulin Resistance; Obesity; Phytotherapy; Polyphenols; Signal Transduction

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

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

Diabetes mellitus is a serious world health problem and one of the most studied diseases; a major concern about its treatment is that β-cell mass and functionality is hard to restore. In addition, it is frequently associated with severe complications, such as diabetic nephropathy and cardiomyopathy. The anti-inflammatory, anti-oxidative and anti-apoptotic properties of curcumin have made it a promising molecule for the treatment of this pathology; however, its solubility and bioavailability problems are still the subject of multiple studies. To cope with those difficulties, several approaches have been evaluated, such as the development of pharmaceutical formulations and curcumin analogs. This review discusses some of the studied therapeutic targets for curcumin in diabetes as well as the structural characteristics and targets of its analogs. The shortening of the central seven-carbon chain of curcumin has given rise to compounds without glucose-lowering effects but potentially useful for the treatment of diabetes complications; whereas preserving this chain retains the glucose-lowering properties. Most of the analogs discussed here have been recently synthesized and tested in animal models of type 1 diabetes; more studies in models of type 2 diabetes are needed.

Topics: Animals; Blood Glucose; Curcumin; Diabetes Complications; Diabetes Mellitus; Humans; Hypoglycemic Agents

Intake of dietary phytochemicals has frequently been associated with health benefits. Noninfectious diseases including cardiovascular disease (CVD), cancer and diabetes are major causes of death, whereas dementia cases are also increasing to 'epidemic' proportion. This review will focus on recent progress on mechanisms underlying the potential role of dietary phytochemicals in CVD, diabetes, cancer and dementia, with consideration of the latest clinical data.. The association of tea (Camellia sinensis), particularly catechins, with reported mechanistic effects for CVD, diabetes, cancer and cognition contributes to our understanding of the suggested benefits of tea consumption on health from limited and inconclusive clinical trial and epidemiological data. Resveratrol, which occurs in grapes (Vitis vinifera) and wine, and curcumin, a component of turmeric (Curcuma longa), are also emerging as potentially relevant to health, particularly for CVD and dementia, with some promising data also concluded for curcumin in cancer. Other phytochemicals mechanistically relevant for health include anthocyanins, isoflavones and glucosinolates, which are also discussed.. Evidence for the role of phytochemicals in health and disease is growing, but associations between phytochemicals and disease need to be more firmly understood and established from more robust clinical data using preparations that have been phytochemically characterized.

Topics: Cardiovascular Diseases; Catechin; Clinical Trials as Topic; Curcuma; Curcumin; Dementia; Diabetes Mellitus; Humans; Micronutrients; Neoplasms; Phytochemicals; Plant Extracts; Resveratrol; Stilbenes; Tea; Vitis; Wine

Diabetic nephropathy is characterized by a plethora of signaling abnormalities. Recent trials have suggested that intensive glucose-lowering treatment leads to hypoglycemic events, which can be dangerous. Curcumin is the active ingredient of turmeric, which has been widely used in many countries for centuries to treat numerous diseases. The preventive and therapeutic properties of curcumin are associated with its antioxidant and anti-inflammatory properties. Here, we highlight the renoprotective role of curcumin in diabetes mellitus (DM) with an emphasis on the molecular basis of this effect. We also briefly discuss the numerous approaches that have been undertaken to improve the pharmacokinetics of curcumin.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Clinical Trials as Topic; Curcumin; Diabetes Mellitus; Diabetic Nephropathies; Humans; Molecular Structure; Signal Transduction

Although there is a therapeutic treatment to combat diabetes, the identification of agents that may deal with its more serious aspects is an important medical field for research. Diabetes, which contributes to the risk of cardiovascular disease, is associated with a low-grade chronic inflammation (inflammatory stress), oxidative stress, and endoplasmic reticulum (ER) stress. Because the integration of these stresses is critical to the pathogenesis of diabetes, agents and cellular molecules that can modulate these stress responses are emerging as potential targets for intervention and treatment of diabetic diseases. It has been recognized that heme oxygenase-1 (HO-1) plays an important role in cellular protection. Because HO-1 can reduce oxidative stress, inflammatory stress, and ER stress, in part by exerting antioxidant, anti-inflammatory, and antiapoptotic effects, HO-1 has been suggested to play important roles in pathogenesis of diabetes. In the present review, we will explore our current understanding of the protective mechanisms of HO-1 in diabetes and present some emerging therapeutic options for HO-1 expression in treating diabetic diseases, together with the therapeutic potential of curcumin analogues that have their ability to induce HO-1 expression.

Topics: Animals; Curcumin; Diabetes Mellitus; Endoplasmic Reticulum Stress; Enzyme Induction; Heme Oxygenase-1; Humans; Hypoglycemic Agents; Inflammation Mediators; Oxidative Stress

Although much has been published about curcumin, which is obtained from turmeric, comparatively little is known about turmeric itself. Turmeric, a golden spice obtained from the rhizome of the plant Curcuma longa, has been used to give color and taste to food preparations since ancient times. Traditionally, this spice has been used in Ayurveda and folk medicine for the treatment of such ailments as gynecological problems, gastric problems, hepatic disorders, infectious diseases, and blood disorders. Modern science has provided the scientific basis for the use of turmeric against such disorders. Various chemical constituents have been isolated from this spice, including polyphenols, sesquiterpenes, diterpenes, triterpenoids, sterols, and alkaloids. Curcumin, which constitutes 2-5% of turmeric, is perhaps the most-studied component. Although some of the activities of turmeric can be mimicked by curcumin, other activities are curcumin-independent. Cell-based studies have demonstrated the potential of turmeric as an antimicrobial, insecticidal, larvicidal, antimutagenic, radioprotector, and anticancer agent. Numerous animal studies have shown the potential of this spice against proinflammatory diseases, cancer, neurodegenerative diseases, depression, diabetes, obesity, and atherosclerosis. At the molecular level, this spice has been shown to modulate numerous cell-signaling pathways. In clinical trials, turmeric has shown efficacy against numerous human ailments including lupus nephritis, cancer, diabetes, irritable bowel syndrome, acne, and fibrosis. Thus, a spice originally common in the kitchen is now exhibiting activities in the clinic. In this review, we discuss the chemical constituents of turmeric, its biological activities, its molecular targets, and its potential in the clinic.

Topics: Animals; Anti-Inflammatory Agents; Antidepressive Agents; Antineoplastic Agents; Curcuma; Curcumin; Diabetes Mellitus; Disease Models, Animal; Drug Evaluation, Preclinical; Humans; Hypoglycemic Agents; Medicine, Traditional; Neoplasms; Neurodegenerative Diseases; Randomized Controlled Trials as Topic; Spices; Wound Healing

Diabetes mellitus (DM) has reached pandemic status and shows no signs of abatement. It can severely impair people's quality of life and affects patients all over the world. Since it is a serious, chronic metabolic disease, it can bring about many kinds of complications, which can in turn increase mortality. In recent decades, more and more studies have shown that oxidative stress and inflammatory reactions play critical roles in the pathogenesis of DM. There is an increasing demand for natural antidiabetic medicines that do not have the same side effects as modern drugs. Curcumin, a phytochemical found in the spice turmeric, has been used in India for centuries, and it has no known side effects. It has been shown to have some beneficial effects against various chronic illnesses. Many of these therapeutic actions can be attributed to its potent anti-oxidant and anti-inflammatory activities. In view of the oxidative stress and inflammatory mechanisms of DM, curcumin can be considered suitable for the prevention and amelioration of diabetes. In this review, we summarize the nosogenesis of DM, giving primary focus to oxidative stress and inflammation. We discuss the anti-oxidant and anti-inflammatory activities of curcumin in DM and its ability to mitigate the effects on DM and its associated complications in detail.

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Biomarkers; Blood Glucose; Curcumin; Diabetes Complications; Diabetes Mellitus; Humans; Hypoglycemic Agents; Inflammation Mediators; Insulin-Secreting Cells; Oxidative Stress; Treatment Outcome

Diabetes mellitus is characterised by hyperglycaemia, lipidaemia and oxidative stress and predisposes affected individuals to long-term complications afflicting the eyes, skin, kidneys, nerves and blood vessels. Increased protein glycation and the subsequent build-up of tissue advanced glycation endproducts (AGEs) contribute towards the pathogenesis of diabetic complications. Protein glycation is accompanied by generation of free radicals through autoxidation of glucose and glycated proteins and via interaction of AGEs with their cell surface receptors (referred to as RAGE). Glycationderived free radicals can damage proteins, lipids and nucleic acids and contribute towards oxidative stress in diabetes. There is interest in compounds with anti-glycation activity as they may offer therapeutic potential in delaying or preventing the onset of diabetic complications. Although many different compounds are under study, only a few have successfully entered clinical trials but none have yet been approved for clinical use. Whilst the search for new synthetic inhibitors of glycation continues, little attention has been paid to anti-glycation compounds from natural sources. In the last few decades the traditional system of medicine has become a topic of global interest. Various studies have indicated that dietary supplementation with combined anti-glycation and antioxidant nutrients may be a safe and simple complement to traditional therapies targeting diabetic complications. Data for forty two plants/constituents studied for anti-glycation activity is presented in this review and some commonly used medicinal plants that possess anti-glycation activity are discussed in detail including their active ingredients, mechanism of action and therapeutic potential.

Topics: Antioxidants; Curcumin; Diabetes Complications; Diabetes Mellitus; Female; Garlic; Glycation End Products, Advanced; Glycosylation; Humans; Hyperglycemia; Hyperlipidemias; Maillard Reaction; Male; Oxidative Stress

Free radicals play a main pathogenic role in several human diseases such as neurodegenerative disorders, diabetes, and cancer. Although there has been progress in treatment of these diseases, the development of important side effects may complicate the therapeutic course. Curcumin, a well known spice commonly used in India to make foods colored and flavored, is also used in traditional medicine to treat mild or moderate human diseases. In the recent years, a growing body of literature has unraveled the antioxidant, anticarcinogenic, and antinfectious activity of curcumin based on the ability of this compound to regulate a number of cellular signal transduction pathways. These promising data obtained in vitro are now being translated to the clinic and more than ten clinical trials are currently ongoing worldwide. This review outlines the biological activities of curcumin and discusses its potential use in the prevention and treatment of human diseases.

Topics: Animals; Antineoplastic Agents; Curcumin; Diabetes Mellitus; Disease Models, Animal; Food Coloring Agents; Free Radicals; Humans; Hypoglycemic Agents; India; Mice; Mice, Knockout; Neoplasms; Neurodegenerative Diseases; NF-E2-Related Factor 2; Stress, Physiological; Taste

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

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

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

This study evaluated the effects of nano-curcumin intake on metabolic status in patients with diabetes on hemodialysis (HD).. This randomized, double-blind, placebo-controlled clinical trial was performed on 60 patients with diabetes on HD. Participants were randomly divided into two groups to take either 80 mg/d nano-curcumin (n = 30) or placebo (n = 30) for 12 weeks.. Nano-curcumin significantly decreased fasting plasma glucose (β = -19.68 mg/dL, 95% CI: -33.48 to -5.88; P < .05) and serum insulin levels (β = -1.70 μIU/mL, 95% CI: -2.96 to -0.44; P < .05) when compared with patients who received placebo. Nanocurcumin treatment was associated with a significant reduction in triglycerides (β = -16.13 mg/dL, 95% CI: -31.51 to -0.75; P < .05), VLDL-cholesterol (β = -3.22 mg/dL, 95% CI: -6.30 to -0.15; P < .05), total cholesterol (β = -17.83 mg/dL, 95% CI: -29.22 to -6.45; P < .05), LDL-cholesterol (β = -15.20 mg/dL, 95% CI: -25.53 to -4.87; P < .05), and total-cholesterol/HDL-cholesterol ratio (β = -1.15, 95% CI: -0.2.10 to -0.21; P < .05) when compared with the placebo. Nanocurcumin also resulted in a significant reduction of serum high sensitivity CRP (β = -0.78 mg/L, 95% CI: -1.41 to -0.15; P < .05), and plasma malondialdehyde (β = -0.25 μmol/L, 95% CI: -0.45 to -0.04; P < .05); but also with a significant increase in plasma total antioxidant capacity (β = 52.43 mmol/L; 95% CI: 4.52 to 100.35; P < .05) and total nitrite levels (β = 3.62 μmol/L, 95% CI: 2.17 to 5.08; P < .001) when compared with placebo.. Nano-curcumin intake for 12 weeks had beneficial effects on metabolic profile in patients with diabetes on HD.

Topics: Blood Glucose; Curcumin; Diabetes Mellitus; Dietary Supplements; Double-Blind Method; Humans; Insulin; Renal Dialysis

We evaluated the effects of curcumin treatment on protein oxidation (PO), lipid peroxidation (LP) and brain-derived neurotrophic factor (BDNF) levels in the hippocampus and frontal cortex (FC) of diabetic db/db mice (DM) and in sera of obese humans. Thus, DM were treated daily with 50 mg/kg of curcumin during an 8-week period. Obese human were treated daily with 500 and 750 mg of curcumin that was administered orally for 12 weeks; BDNF, PO and LP levels in sera were determined at in weeks 0, 2, 6 and 12 of treatment. BDNF levels decreased in hippocampus and FC of DM as compared with untreated wild-type mice. Curcumin improved or restored BDNF levels to normal levels in DM, but curcumin did not have any effect on BDNF levels in sera of obese humans. In hippocampus and FC of DM, hyperglycaemia and curcumin did not have effect on LP levels. Hyperglycaemia increased PO levels in hippocampus and FC, whereas curcumin decreased these levels in hippocampus but not in FC. In sera of obese humans, the 500-mg dose decreased LP levels in weeks 6 and 12 when compared with basal levels, but the 750-mg dose did not have any effect; both doses of curcumin decreased PO levels in weeks 2, 6 and 12 of treatment when compared with basal levels. Present results suggest a therapeutic potential of curcumin to decrease oxidation caused by obesity in humans and also show that curcumin restores BDNF levels in DM.

Topics: Adult; Animals; Brain-Derived Neurotrophic Factor; Curcumin; Diabetes Mellitus; Diabetes Mellitus, Experimental; Humans; Male; Mice; Obesity; Oxidative Stress; Single-Blind Method

Topics: alpha-Amylases; alpha-Glucosidases; Animals; Curcumin; Diabetes Mellitus; Glycoside Hydrolase Inhibitors; Hypoglycemic Agents; Molecular Docking Simulation; Rats; Rats, Wistar; Spectroscopy, Fourier Transform Infrared

This study aimed to investigate the effects of curcumin treatment on ovaries at different periods of the diabetes disease. Fifty-six female Wistar albino rats (250-300 g) aged 12 weeks were divided into seven groups. No treatment was applied to the control group. The sham group was given 5 mL/kg of corn oil, and the curcumin group 30 mg/kg curcumin. In the diabetes mellitus (DM) groups, diabetes was induced by a single intraperitoneal dose of 50 mg/kg streptozotocin (STZ). The DM-treated groups received 30 mg/kg curcumin after either 7 days (DC1 group) or 21 days (DC2 group), or simultaneously with STZ injection (DC3 group). Number of follicles in the ovaries was estimated using stereological method. Follicle-stimulating hormone (FSH), luteinizing hormone (LH), and superoxide dismutase (SOD) levels and catalase (CAT) activity were measured in serum specimens. We found that follicle number and volume of corpus luteum, blood vessel, and cortex, gonadosomatic index, and FSH and SOD levels all decreased significantly in diabetic ovaries, while relative weight loss, connective tissue volume, and CAT activity increased (p < 0.01). Curcumin treatment had a protective effect on the number of primordial follicles in the DC2 group and on antral follicle numbers in the DC3 group. Curcumin also exhibited positive effects on CAT activity and SOD levels, blood glucose levels, and corpus luteum, connective tissue, and blood vessel volumes in the DC2 and DC3 groups. Curcumin also ameliorated FSH levels in the DC1 and DC3 groups (p < 0.01). These findings suggest that curcumin exhibits protective effects on ovarian structures and folliculogenesis, especially when used concurrently with the development of diabetes or in later stages of the disease.

Topics: Animals; Antioxidants; Curcumin; Diabetes Mellitus; Female; Follicle Stimulating Hormone; Ovary; Oxidative Stress; Rats; Rats, Wistar; Superoxide Dismutase

Excessive levels of the mitochondrial reactive oxygen radical (mitSOX) and Ca

Topics: Animals; Antioxidants; Curcumin; Diabetes Mellitus; Male; Mice; Neuralgia; Oxidative Stress; Selenium; Streptozocin; TRPM Cation Channels

Diabetes is one of the most common metabolic diseases in humans and the use of herbal medicines is of great clinical importance to inhibit carbohydrate-hydrolyzing enzymes and reduce blood glucose levels in diabetic patients. Inhibition of glycosidase activity is an effective way to treat and prevent diabetes. Therefore, in this study, curcumin-based benzaldehyde derivatives were synthesized and used as influential agents in the treatment of diabetes with inhibitory properties against two carbohydrate-hydrolyzing enzymes α-glucosidase (α-Glu) and α-amylase (α-Amy) as significant therapeutic targets for reducing postprandial hyperglycemia. Overall, the findings showed that due to the specific inhibitory activity against α-Glu in comparison with α-Amy, as well as more stability and antioxidant activity than curcumin, C5 and C8 derivatives are potentially important anti-diabetic drugs, not only to decrease glycemic index but also to limit the activity of the main production pathways of reactive oxygen species (ROS) in diabetic patients.Communicated by Ramaswamy H. Sarma.

Topics: alpha-Amylases; alpha-Glucosidases; Carbohydrates; Curcumin; Diabetes Mellitus; Glycoside Hydrolase Inhibitors; Glycoside Hydrolases; Humans; Hypoglycemic Agents

Diabetic retinopathy (DR) is one of the most common complications of diabetes and has become a major global cause of blindness. Curcumin, an extract of Curcuma longa (turmeric), is effective in preventing and treating diabetes. Recent studies have shown that curcumin can delay DR development. However, there has been no systematic review of its treatment of DR. This study will conduct a systematic review and meta-analysis of currently published randomized controlled trials (RCT) of curcumin for treating DR patients to evaluate its efficacy and safety.. We will search the relevant studies of curcumin in the treatment of DR in PubMed, Medline, EMBASE, Cochrane Library, China National Knowledge Infrastructure (CNKI), VIP, and Wanfang databases from their respective inception dates to May 2022. A meta-analysis of the data extracted from qualified RCTs will be conducted, including the progression of DR, visual acuity, visual field, macular edema, quality of life, and adverse events. The meta-analysis will be performed using Review Manager 5.4.1 software, and the results will be based on either random-effects or fixed-effects models, depending on the heterogeneity. The Grading of Recommendations, Development, and Evaluation (GRADE) system will be used to evaluate the reliability and quality of evidence.. The results of this study will provide sound and high-quality evidence for the efficacy and safety of curcumin in the treatment of DR.. This study will be the first meta-analysis to comprehensively assess the efficacy and safety of curcumin in the treatment of DR and will provide helpful evidence for the clinical management of this disease.. INPLASY202250002.

Topics: Curcumin; Diabetes Mellitus; Diabetic Retinopathy; Drugs, Chinese Herbal; Humans; Meta-Analysis as Topic; Randomized Controlled Trials as Topic; Systematic Reviews as Topic

Stem cell injection is an effective approach for treating diabetic wounds; however, shear stress during injections can negatively affect their stemness and cell growth. Cell-laden porous microspheres can provide shelter for bone mesenchymal stem cells (BMSC). Herein, curcumin-loaded flower-like porous microspheres (CFPM) are designed by combining phase inversion emulsification with thermally induced phase separation-guided four-arm poly (l-lactic acid) (B-PLLA). Notably, the CFPM shows a well-defined surface topography and inner structure, ensuring a high surface area to enable the incorporation and delivery of a large amount of -BMSC and curcumin. The BMSC-carrying CFPM (BMSC@CFPM) maintains the proliferation, retention, and stemness of -BMSCs, which, in combination with their sustainable curcumin release, facilitates the endogenous production of growth/proangiogenic factors and offers a local anti-inflammatory function. An in vivo bioluminescence assay demonstrates that BMSC@CFPM can significantly increase the retention and survival of BMSC in wound sites. Accordingly, BMSC@CFPM, with no significant systemic toxicity, could significantly accelerate diabetic wound healing by promoting angiogenesis, collagen reconstruction, and M2 macrophage polarization. RNA sequencing further unveils the mechanisms by which BMSC@CFPM promotes diabetic wound healing by increasing -growth factors and enhancing angiogenesis through the JAK/STAT pathway. Overall, BMSC@CFPM represents a potential therapeutic tool for diabetic wound healing.

Topics: Curcumin; Diabetes Mellitus; Humans; Janus Kinases; Microspheres; Polymers; Porosity; Signal Transduction; STAT Transcription Factors; Wound Healing

Diabetic chronic wounds remain a major clinical challenge with long-term inflammatory responses and extreme oxidative damage. Hence, a pH-responsive injectable multifunctional hydrogel [Gel/CUR-FCHO/Mg (GCM) micromotors] via a Schiff base reaction between gelatin and benzaldehyde-grafted Pluronic F127 drug-loaded micelles (FCHO) was fabricated for the first time. Dynamic Schiff base linkage endowed the GCM hydrogel with the ability to be self-healing, injectable, and pH-responsive for on-demand drug delivery at the wound site. Curcumin (CUR), a hydrophobic drug with antioxidative, anti-inflammatory, and antibacterial activities, was encapsulated into the hydrogel matrix by micellization (CUR-FCHO micelles). Simultaneously, magnesium-based micromotors (Mg micromotors) were physically entrapped into the system for providing active hydrogen (H

Topics: Animals; Anti-Bacterial Agents; Antioxidants; Curcumin; Diabetes Mellitus; Gelatin; Hydrogels; Hydrogen-Ion Concentration; Mice; Micelles; Poloxamer; Schiff Bases

Diabetes is involved in delayed wound healing that can be cured by natural products such as garlic, turmeric, and fibroin extracts. Alloxan monohydrate is used for inducing diabetes in mice. The percent wound contraction of garlic (150 mg/ml), turmeric (100 mg/ml), and fibroin (50 mg/ml), individually and in combinations garlic (150 mg/ml) + fibroin (50 mg/ml), turmeric (100 mg/ml) + fibroin (50 mg/ml), garlic (150 mg/ml) + turmeric (100 mg/ml), and garlic (150 mg/ml) + turmeric (100 mg/ml) + fibroin (50 mg/ml) was checked by evaluating the healing time, % wound contraction and histological analysis. The serum level of MMPs (MMP 2, MMP7, MMP 9), pro-inflammatory cytokines (TNF-α, IL-6, IL-8), and TIMPs were evaluated. With the combination of three extracts (Ga+Tu+Fi) garlic (150 mg/ml), turmeric (100 mg/ml) and fibroin (50 mg/ml), wounds healed in 12 days and had 97.3 ± 2.2% wound contraction. While the positive control (polyfax) and diabetic control (saline) wounds healed in 17- and 19-days with wound contraction of 96.7 ± 1.4% and 96.3 ± 1.1%, respectively. Histological analysis showed that the combination of Ga+Tu+Fi exhibited an increase in the growth of collagen fibers, fibroblasts number, and keratinocytes, and lessened inflammation of blood vessels. The combination of Ga+Tu+Fi significantly alleviated the serum concentration of TNF-α (14.2 ± 0.7 pg/ml), IL-6 (10.0 ± 1.0 pg/ml), IL-8 (16.0 ± 1.5 pg/ml), MMP2 (228.0 ± 18.1 pg/ml), MMP7 (271.0 ± 9.9 pg/ml), and MMP9 (141.0 ± 5.3 pg/ml) to diabetic control. The level of TIMPs (193.0 ± 9.1 pg/ml) was increased significantly with respect to diabetic control. We conclude that the combination of these biomaterials possessed high regenerative and healing capabilities and can be an effective remedy in the healing of chronic wounds in diabetic patients.

Topics: Animals; Burns; Curcuma; Diabetes Mellitus; Fibroins; Garlic; Interleukin-6; Interleukin-8; Matrix Metalloproteinase 7; Mice; Tumor Necrosis Factor-alpha; Wound Healing

Background: To investigate the effects of a fixed combination of Curcumin (200 mg), Artemisia (80 mg), Bromelain (80 mg), and Black pepper (2 mg) on vascular parameters in mild to moderate diabetic macular edema (DME). Design: Prospective, case-control study. Methods: Fifty-six patients affected by diabetes mellitus type II were enrolled in the study. Twenty-eight patients with DME received 2 tablets/day, before meals of a dietary complementary supplement containing in fixed combination Curcumin (200 mg), Artemisia (80 mg), Bromelain (80 mg), and Black pepper (2 mg) (Intravit®, OFFHEALTH Spa, Firenze, Italy) for 6 months. Twenty-eight age-matched subjects affected by diabetes mellitus type II were given placebo and served as control group. Patients underwent best correct visual acuity (BCVA), swept optical coherence tomography (OCT), and OCT-Angiography (OCTA). OCTA images of the superficial capillary plexus (SCP) and deep capillary plexus (DCP) were obtained for each eye. By the end of the follow-up patients were defined responder to the therapy when a decrease of more than 30 μm was registered in central retinal thickness (CRT) measurement, while a poor responder was determined by the absence of reduction or an increase in central retinal thickness at 6 months. We assessed the foveal avascular zone (FAZ) area, vessel density and quantified the number of microaneurysms in each layer. Results: A significant improvement of BCVA and CRT reduction was recorded at 6 months follow-up in the dietary complementary supplementation group compared to control (respectively p = 0.028 and p = 0.0003). VD of the total capillary plexus, microaneurysms count, glycaemia and HbA1c did not vary over the follow-up period between groups. Within the Intravit® group, poor responders tended to show a larger FAZ area, more microaneurysms, and a lower VD in the DCP compared to the good responders group (p < 0.0001). Conclusions: A fixed combination of Curcumin, Artemisia, Bromelain, and Black pepper oral administration may have a positive impact on central retinal thickness, visual acuity, and VD of the DCP in compensated type 2 diabetic patients with mild DME.

Topics: Administration, Oral; Artemisia; Bromelains; Case-Control Studies; Curcumin; Diabetes Mellitus; Diabetic Retinopathy; Fluorescein Angiography; Humans; Macular Edema; Microaneurysm; Piper nigrum; Prospective Studies; Retinal Vessels; Retrospective Studies; Tomography, Optical Coherence

Increasing evidence suggested that inhibiting the apoptosis of Schwann cells (SCs) and promoting nerve growth factor (NGF) expression in sciatic nerves play key roles in preventing the onset of diabetic peripheral neuropathy (DPN). Curcumin, a primary bioactive substance in turmeric with multiple characteristics, has been shown to have many therapeutic effects in a variety of diseases. However, curcumin is poorly studied in the DPN models. We aimed to explore the therapeutic benefits and underlying mechanism of curcumin in high fat/sugar diets joint streptozotocin (STZ)-induced DPN rat models. Sprague-Dawley (SD) rats were divided into five groups (6 rats per group), control group, DPN group, Curcumin groups (50, 100, and 150 mg/kg). Curcumin was administered intragastrically once per day for 4 continuous weeks. Body weight (BW) and fasting blood glucose (FBG) were monitored in all groups. The mechanical withdraw threshold (MWT) was measured. We also assessed neuropathic change by testing nerve conductance velocity (NCV) in sciatic nerves. TEM was applied to observe the sciatic nerves ultrastructure. The SCs apoptosis in sciatic nerves was stained using TUNEL kit. NGF contents in sciatic nerves and serum were detected using western blotting and ELISA analysis. The results showed curcumin had no obvious effect on the BW and FBG change. Curcumin (100 and 150 mg/kg) attenuated the MWT, NCV, and sciatic nerves ultrastructure in DPN rats. Curcumin (50, 100 and 150 mg/kg) reduced SCs apoptosis in sciatic nerves. In addition, curcumin at 150 mg/kg had the best efficacy in increasing protein expression of NGF in sciatic nerves and serum NGF level. Our work demonstrated that curcumin has neuroprotective effects for the treatment of DPN.

Topics: Animals; Curcumin; Diabetes Mellitus; Diabetic Neuropathies; Nerve Growth Factor; Rats; Rats, Sprague-Dawley

Over the past twenty years, the prevalence of diabetes as one of the most common metabolic diseases has become a public health problem worldwide. Blood glucose control is important in delaying the onset and progression of diabetes-related complications. α-Glycosidase (α- Glu) and α-amylase (α-Amy) are important enzymes in glucose metabolism. Diabetic control through the inhibition of carbohydrate hydrolyzing enzymes is established as an effective strategy.. In this study, curcumin-based benzaldehyde derivatives with high stability, bioavailability, and favorable efficiency were synthesized.. The results showed that L13, L8, and L11 derivatives have the highest inhibitory effect on α-Glu with IC. L13, compared to the other compounds, exhibited acceptable inhibitory activity against both enzymes. The L13 derivative could be an appropriate candidate for further study through the rational drug design to the exploration of a new class of powerful anti-diabetic drugs considering the antioxidant properties of the synthesized compounds. The derivative helps reduce the glycemic index and limits the activity of the major reactive oxygen species (ROS) producing pathways.

Topics: alpha-Amylases; alpha-Glucosidases; Curcumin; Diabetes Mellitus; Glycoside Hydrolase Inhibitors; Humans; Hypoglycemic Agents; Molecular Docking Simulation

Diabetes mellitus is a multifactorial chronic metabolic disorder, characterized by altered metabolism of macro-nutrients, such as fats, proteins, and carbohydrates. Diabetic retinopathy, diabetic cardiomyopathy, diabetic encephalopathy, diabetic periodontitis, and diabetic nephropathy are the prominent complications of diabetes. Inflammatory mediators are primarily responsible for these complications. Curcumin, a polyphenol derived from turmeric, is well known for its anti-oxidant, anti-inflammatory, and anti-apoptotic properties. The regulation of several signaling pathways effectively targets inflammatory mediators in diabetes. Curcumin's anti-inflammatory and anti-oxidative activities against a wide range of molecular targets have been shown to have therapeutic potential for a variety of chronic inflammatory disorders, including diabetes. Curcumin's biological examination has shown that it is a powerful anti-oxidant that stops cells from growing by releasing active free thiol groups at the target location. Curcumin is a powerful anti-inflammatory agent that targets inflammatory mediators in diabetes, and its resistant form leads to better therapeutic outcomes in diabetes complications. Moreover, Curcumin is an anti-oxidant and NF-B inhibitor that may be useful in treating diabetes. Curcumin has been shown to inhibit diabetes-related enzymes, such as a-glucosidase, aldose reductase and aldose reductase inhibitors. Through its anti-oxidant and anti-inflammatory effects, and its suppression of vascular endothelial development and nuclear transcription factors, curcumin has the ability to prevent, or reduce, the course of diabetic retinopathy. Curcumin improves insulin sensitivity by suppressing phosphorylation of ERK/JNK in HG-induced insulin-resistant cells and strengthening the PI3K-AKT-GSK3B signaling pathway. In the present article, we aimed to discuss the anti-inflammatory mechanisms of curcumin in diabetes regulated by various molecular signaling pathways.

Topics: Aldehyde Reductase; Anti-Inflammatory Agents; Antioxidants; Curcumin; Diabetes Mellitus; Diabetic Nephropathies; Humans; Inflammation Mediators; Phosphatidylinositol 3-Kinases

Diabetes causes lipid peroxide to accumulate within cardiomyocytes. Furthermore, lipid peroxide buildup is a risk factor for ferroptosis. This study is aimed at examining whether curcumin can ameliorate ferroptosis in the treatment of diabetic cardiomyopathy. Hematoxylin and eosin and Masson sections were used to examine the morphology, arrangement, and degree of fibrosis of the myocardium of diabetic rabbit models. The expression levels of nuclear Nrf2, Gpx4, Cox1, and Acsl4 in diabetic animal and cell models were quantitatively analyzed using immunofluorescence and western blotting. Nrf2-overexpression lentivirus vectors were transfected into cardiomyocytes, and the protective effects of curcumin and Nrf2 on cardiomyocytes under high glucose stimulation were assessed using terminal deoxynucleotidyl transferase dUTP nick-end labelling and reactive oxygen species probes. Diabetes was found to disorder myocardial cell arrangement and significantly increase the degree of myocardial fibrosis and collagen expression in myocardial cells. Curcumin treatment can increase nuclear transfer of Nrf2 and the expression of Gpx4 and HO-1, reduce glucose induced myocardial cell damage, and reverse myocardial cell damage caused by the ferroptosis inducer erastin. This study confirmed that curcumin can promote the nuclear translocation of Nrf2, increase the expression of oxidative scavenging factors, such as HO-1, reduce excessive Gpx4 loss, and inhibit glucose-induced ferroptosis in cardiomyocytes. This highlights a potentially new therapeutic route for investigation for the treatment diabetic cardiomyopathy.

Topics: Animals; Apoptosis; Curcumin; Diabetes Mellitus; Diabetic Cardiomyopathies; Ferroptosis; Glucose; Lipid Peroxides; NF-E2-Related Factor 2; Rabbits

Diabetes is an increasingly prevalent global disease caused by the impairment in insulin production or insulin function. Diabetes in the long term causes both microvascular and macrovascular complications that may result in retinopathy, nephropathy, neuropathy, peripheral arterial disease, atherosclerotic cardiovascular disease, and cerebrovascular disease. Considerable effort has been expended looking at the numerous genes and pathways to explain the mechanisms leading to diabetes-related complications. Curcumin is a traditional medicine with several properties such as being antioxidant, anti-inflammatory, anti-cancer, and anti-microbial, which may have utility for treating diabetes complications. This study, based on the system biology approach, aimed to investigate the effect of curcumin on critical genes and pathways related to diabetes.. We first searched interactions of curcumin in three different databases, including STITCH, TTD, and DGIdb. Subsequently, we investigated the critical curated protein targets for diabetes on the OMIM and DisGeNET databases. To find important clustering groups (MCODE) and critical hub genes in the network of diseases, we created a PPI network for all proteins obtained for diabetes with the aid of a string database and Cytoscape software. Next, we investigated the possible interactions of curcumin on diabetes-related genes using Venn diagrams. Furthermore, the impact of curcumin on the top scores of modular clusters was analysed. Finally, we conducted biological process and pathway enrichment analysis using Gene Ontology (GO) and KEGG based on the enrichR web server.. We acquired 417 genes associated with diabetes, and their constructed PPI network contained 298 nodes and 1651 edges. Next, the analysis of centralities in the PPI network indicated 15 genes with the highest centralities. Additionally, MCODE analysis identified three modular clusters, which highest score cluster (MCODE 1) comprises 19 nodes and 92 edges with 10.22 scores. Screening curcumin interactions in the databases identified 158 protein targets. A Venn diagram of genes related to diabetes and the protein targets of curcumin showed 35 shared proteins, which observed that curcumin could strongly interact with ten of the hub genes. Moreover, we demonstrated that curcumin has the highest interaction with MCODE1 among all MCODs. Several significant biological pathways in KEGG enrichment associated with 35 shared included the AGE-RAGE signaling pathway in diabetic complications, HIF-1 signaling pathway, PI3K-Akt signaling pathway, TNF signaling, and JAK-STAT signaling pathway. The biological processes of GO analysis were involved with the cellular response to cytokine stimulus, the cytokine-mediated signaling pathway, positive regulation of intracellular signal transduction and cytokine production in the inflammatory response.. Curcumin targeted several important genes involved in diabetes, supporting the previous research suggesting that it may have utility as a therapeutic agent in diabetes.

Topics: Antioxidants; Computational Biology; Curcumin; Cytokines; Diabetes Mellitus; Humans; Insulins; Phosphatidylinositol 3-Kinases

The hallmark feature of Diabetes mellitus (DM) is hyperglycemia which can lead to excess production of reactive oxygen species (ROS) in the myocardium, contributing to diabetic cardiomyopathy (DCM). Nuclear factor erythroid2-related factor2 (Nrf2), a transcriptional activator, enhances its ability to resist oxidative stress by activating multiple downstream anti-oxidants, anti-inflammatory proteins, and detoxifying enzymes. However, the mechanism of Nrf2 signaling in HG-induced DCM is unclear. In this study, we used HG pretreated H9c2 cells as the experimental basis in vitro, and established a high fat-diet, streptozotocin (STZ) induced Type 2 diabetic rat model in vivo. Meanwhile, we used shRNA-Nrf2 and curcumin (CUR) (as an activator) to affect H9c2 cells, to verify the role of the Nrf2 signaling pathway in DCM. The results showed that the excessive production of ROS caused by HG, which could inhibit the activation of Nrf2-related signaling, resulting in a decrease in cell energy metabolism and an increase in cell apoptosis. Surprisingly, we found that the activation of the Nrf2 signaling pathway significantly increased cardiomyocyte viability, reduced ROS formation, increased antioxidant enzyme activity, and inhibited cardiomyocyte apoptosis. In conclusion, these findings conclusively infer that CUR activation of the Nrf2/HO-1 signaling pathway exerts myocardial protection by reducing ROS formation.

Topics: Animals; Antioxidants; Apoptosis; Curcumin; Diabetes Mellitus; Diabetic Cardiomyopathies; NF-E2-Related Factor 2; Oxidative Stress; Rats; Reactive Oxygen Species; Signal Transduction

Maintaining healthy body weight is an important component of any effective diabetes management plan. However, glycemic management using insulin generally leads to weight gain. In addition, weight loss medications prescribed for diabetes management are often associated with adverse side effects, which limit their long-term usage. Alternatively, nutrition intervention provides a safe, readily accessible, and inexpensive option for diabetes management. This study describes a composition of phytonutrients comprising berberine, cinnamaldehyde, and curcumin for glycemic and weight management. Functional complementarity between berberine, cinnamaldehyde, and curcumin provides an effective means to improve insulin sensitivity without increasing adiposity. In primary human omental preadipocytes, cinnamaldehyde and curcumin additively enhance insulin-stimulated activation of Akt2 and glucose uptake, whereas berberine inhibits de novo fatty acid biosynthesis and fat cell differentiation. In a diet-induced obesity murine model, a dietary supplement with berberine, cinnamaldehyde, and curcumin prevents weight gain, improves glucose tolerance, and reduces HbA1c, blood lipids, visceral adiposity, and liver steatosis. Collectively, the composition of phytonutrients comprising berberine, cinnamaldehyde, and curcumin protects against obesity and pre-diabetic conditions in a diet-induced obesity murine model. Safety and efficacy assessment of nutrition intervention using combined berberine, cinnamaldehyde, and curcumin for glycemic and weight management in future clinical trials are warranted.

Topics: Acrolein; Animals; Berberine; Blood Glucose; Curcumin; Diabetes Mellitus; Disease Models, Animal; Fatty Acids; Glycated Hemoglobin; Humans; Insulin; Insulin Resistance; Lipids; Mice; Obesity; Phytochemicals; Weight Gain

This project was aimed at formulating a novel nanoemulsion system and evaluating it for open incision wound healing in diabetic animals.. The nanoemulsions were characterized for droplet size and surface charge, drug content, antioxidant and antimicrobial profiling, and wound healing potential in diabetic animals. The skin samples excised were also analyzed for histology, mechanical strength, and vibrational and thermal analysis.. The optimized nanoemulsion (CR-NE-II) exhibited droplet size of26.76 ± 0.9 nm with negative surface charge (-10.86 ± 1.06 mV), was homogenously dispersed with drug content of68.05 ± 1.2%, released almost82.95 ± 2.2%of the drug within first 2 h of experiment with synergistic antioxidant (95 ± 2.1%) and synergistic antimicrobial activity against selected bacterial strains in comparison to blank nanoemulsion, and promoted significantly fast percent reepithelization (96.47%). The histological, vibrational, thermal, and strength analysis of selected skin samples depicted a uniform and even distribution of collagen fibers which translated into significant increase in strength of skin samples in comparison to the control group.. The optimized nanoemulsion system significantly downregulated the oxidative stress, enhanced collagen deposition, and precluded bacterial contamination of wound, thus accelerating the skin tissue regeneration process.

Topics: alpha-Tocopherol; Animals; Antioxidants; Collagen; Curcumin; Diabetes Mellitus; Emulsions; Wound Healing

Diabetes is very much known as a wide-spread disorder all around the world with serious complications for the diabetic patient. In order to reduce these complications, inhibition the activity of aldose reductase (AR) and cyclooxygenase-2 (COX-2) enzymes is a proposed pathway. Within this work potency of curcumin (CUR) for the proposed enzymatic inhibition has been performed by the

Topics: Aldehyde Reductase; Curcumin; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Diabetes Mellitus; Enzyme Inhibitors; Humans; Male; Molecular Docking Simulation

Chronic cerebral hypoperfusion (CCH) is regarded as a high-risk factor for cognitive decline in vascular dementia (VaD). We have previously shown that diabetes mellitus (DM) synergistically promotes CCH-induced cognitive dysfunction via exacerbating neuroinflammation. Furthermore, curcumin has been shown to exhibit anti-inflammatory and neuroprotective activities. However, the effects of curcumin on CCH-induced cognitive impairments in DM have remained unknown.. Rats were fed with a high-fat diet (HFD) and injected with low-dose streptozotocin (STZ), followed by bilateral common carotid artery occlusion (BCCAO), to model DM and CCH in vivo. After BCCAO, curcumin (50 mg/kg) was administered intraperitoneally every two days for eight weeks to evaluate its therapeutic effects. Additionally, mouse BV2 microglial cells were exposed to hypoxia and high glucose to model CCH and DM pathologies in vitro.. Curcumin treatment significantly improved DM/CCH-induced cognitive deficits and attenuated neuronal cell death. Molecular analysis revealed that curcumin exerted protective effects via suppressing neuroinflammation induced by microglial activation, regulating the triggering receptor expressed on myeloid cells 2 (TREM2)/toll-like receptor 4 (TLR4)/nuclear factor-κB (NF-κB) pathway, alleviating apoptosis, and reducing nod-like receptor protein 3 (NLRP3)-dependent pyroptosis.. Taken together, our findings suggest that curcumin represents a promising therapy for DM/CCH-induced cognitive impairments.

Topics: Animals; Anti-Inflammatory Agents; Apoptosis; Cells, Cultured; Cognitive Dysfunction; Curcumin; Diabetes Mellitus; Disease Models, Animal; Humans; Hypoxia, Brain; Male; Mice; Microglia; Neurogenic Inflammation; Pyroptosis; Rats; Rats, Sprague-Dawley

Topics: alpha-Amylases; alpha-Glucosidases; Animals; Antioxidants; Curcumin; Diabetes Mellitus; Drug Design; Glycoside Hydrolases; Hypoglycemic Agents; Intestines; Models, Molecular; Molecular Docking Simulation; Molecular Structure; Pancreas; Protein Binding; Protein Conformation; Rats; Structure-Activity Relationship

All over the world, the prevalence of diabetes mellitus is increasing. The main goal of this experiment was to identify the most effective fraction of aqueous-methanol extract of Curcuma amada rhizome for its antidiabetic and antioxidative properties. The fractions (n-hexane or chloroform or ethyl-acetate or n-butanol) of aqueous-methanol extract were administered to the streptozotocin-induced diabetic groups at a dose of 10 mg/100 g body weight/day for 4 weeks. The antidiabetic and antioxidative efficacies of the fractions on glycemic, enzymatic, genomic, and histological sensors and pancreatic β-cells population and general toxicity were assessed. After the fraction treatment, out of the fraction used, the significant recovery in most sensors was noted at the ethyl-acetate fraction in glycemic, enzymatic, genomic, β cells population, diameter of the pancreatic islet and toxicity level. In conclusion, it may be stated that the ethyl-acetate fraction of C. amada was the most effective solvent in this study. PRACTICAL APPLICATIONS: The ethyl-acetate fraction of aqueous-methanol extract of Curcuma amada has antidiabetic property, it gives a clue to the herbal medicine manufacturing company to produce phytotherapeutic drugs to cure the complication related to diabetes.

Topics: Animals; Antioxidants; Curcuma; Diabetes Mellitus; Hypoglycemic Agents; Plant Extracts; Rats; Rhizome; Solvents

Curcumin is a promising wound healing agent but its clinical application is limited due to hydrophobicity and lack of stability. In this article, we report the results of a study on wound healing efficacy of curcumin conjugated to hyaluronic acid (HA) which is a natural polysaccharide known to influence the healing process. Studies on proliferation, antioxidant activity and scratch wound healing carried out in human keratinocyte cells revealed that HA-conjugated curcumin treatment enhanced cell proliferation, decreased oxidative damage induced by H

Topics: Animals; Antioxidants; Cell Line; Cell Survival; Curcumin; Darkness; Diabetes Mellitus; Humans; Hyaluronic Acid; Male; Mice; Molecular Weight; Wound Healing

Two different series of novel β-ketoamide curcumin analogs enriched in biological activities have been synthesized. The synthesized compounds were screened for their in vitro anti-diabetic and AGEs inhibitory activities and exhibited potent to good anti-diabetic and AGEs inhibitory activities. The molecular docking study was also performed with the α-amylase enzyme.

Topics: alpha-Amylases; alpha-Glucosidases; Amides; Curcumin; Diabetes Mellitus; Dose-Response Relationship, Drug; Enzyme Inhibitors; Glycation End Products, Advanced; Humans; Hypoglycemic Agents; Molecular Docking Simulation; Molecular Structure; Structure-Activity Relationship

Chitosan (CS) has been extensively studied as drug delivery systems for wound healing. Results/methodology: CS nanoparticles were loaded with curcumin (Cur) and DsiRNA against prostaglandin transporter gene and they were incorporated into 20 and 25% w/v Pluronic F-127. The gels were later analyzed for their rheology, gelation temperature (T. A thermo-sensitive gel containing Cur/DsiRNA CS nanoparticles was successfully developed and has a great potential to be further developed.

Topics: Chitosan; Curcumin; Diabetes Mellitus; Drug Carriers; Drug Liberation; Gels; Nanoparticles; RNA, Small Interfering; Wounds and Injuries

Diabetic patients frequently suffer from non-alcoholic steatohepatitis. The current study aimed to investigate the role of curcumin and the response of hepatic stellate cells in streptozotocin (STZ)-induced hepatic damage. Sixty male rats were divided into three groups. The normal control injected with a citrate buffer vehicle and the diabetic control group which was injected intraperitoneally (IP) with a single-dose of streptozotocin (50mg/kg body weight) and a diabetic group was treated with an oral dose of curcumin at 80 mg/kg body weight daily for 60 days. Curcumin effectively counteracts oxidative stress-mediated hepatic damage and improves biochemical parameters. Alpha-smooth muscle actin (α-SMA) was significantly reduced, and insulin antibodies showed strong positive immunoreactivity with curcumin administration. These results optimistically demonstrate the potential use of curcumin, which is attributed to its antiradical/antioxidant activities and its potential β-cell regenerative properties. Also, it has the capability to encourage the trans-differentiation of hepatic stellate cells into insulin-producing cells for a period of time. In addition, as it is an anti-fibrotic mediator that inhibits hepatic stellate cell activation and the transition to myofibroblast-like cells, this suggests the possibility of considering curcumin's novel therapeutic effects in reducing hepatic dysfunction in diabetic patients.

Topics: Actins; Animals; Cell Transdifferentiation; Curcumin; Diabetes Complications; Diabetes Mellitus; Hepatic Stellate Cells; Humans; Insulin; Liver; Non-alcoholic Fatty Liver Disease; Oxidation-Reduction; Oxidative Stress; Rats; Streptozocin

The present study was aimed to study the neuroprotective therapeutic effect of curcumin on the male albino rat brain. Subarachnoid hemorrhage leads to severe mortality rate and morbidity, and oxidative stress is a crucial factor in subarachnoid hemorrhage. Therefore, we investigated the effect of curcumin on oxidative stress and glutamate and glutamate transporter-1 on a subarachnoid hemorrhage-induced male albino rats. The curcumin commonly used for the treatment and saline used for the control. Curcumin (10 mg/kg bwt) dissolved in saline and administered orally to the rats for one week. Glutamate, glutamate transporter-1, malondialdehyde (MDA), superoxide dismutase (SOD), catalase, glutathione reductase and lactate dehydrogenase (LDH) activities were determined. Glutamate level was lower in the curcumin-treated rats compared to their respective controls. Glutamate transporter-1 did not alter in the curcumin-treated rats compared to their controls. Glutamate transporter-1 protein expression is significantly reduced in the curcumin-treated rats. MDA levels decreased 18 and 29 % in the hippocampus and the cortex region respectively. SOD (17% and 32%), and catalase (19% and 24%) activities were increased in the curcumin-treated hippocampus and the cortex region respectively. Glutathione reductase (13% and 19%) and LDH (21% and 30%) activities were increased in the treated hippocampus and the cortex region respectively. The mRNA expression of NK-kB and TLR4 was significantly reduced following curcumin treatment. Taking all these data together, the curcumin found to be effective against oxidative stress and glutamate neurotoxicity in the male albino rats.

Topics: Animals; Curcumin; Diabetes Mellitus; Male; Malondialdehyde; Neuroprotective Agents; Oxidative Stress; Rats; Rats, Wistar; Superoxide Dismutase

Our previous studies have confirmed that the sphingosine kinase 1 (SphK1)-sphingosine 1-phosphate (S1P) signaling pathway in the kidney under diabetic conditions is closely correlated with the pathogenesis of diabetic nephropathy (DN). The activation of SphK1-S1P pathway by high glucose (HG) can increase the expression of fibronectin (FN), an important fibrotic component, in glomerular mesangial cells (GMCs) by promoting the DNA-binding activity of transcription factor AP-1. However, the mechanism responsible for the sustained activation of SphK1-S1P pathway remains unclear. Given the binding motifs for AP-1 within the first intron of the SphK1 gene, we speculated that the activated AP-1 in the kidney under HG condition possibly regulates SphK1 expression in a positive feedback manner, thereby promoting the sustained activation of SphK1-S1P pathway and mediating the pathological progression of DN. Here, we observed the effect of AP-1 on SphK1 expression in GMCs and explored the molecular mechanism involved in the sustained activation of SphK1-S1P pathway. We found two consensus binding motifs for AP-1 in the promoter sequences and non-coding region downstream of the transcriptional initiation of the rat SphK1 gene by chromatin immunoprecipitation assay. The treatment of GMCs with both HG and S1P significantly increased the protein expression of c-Jun and c-Fos, and obviously enhanced the phosphorylation of c-Jun at Ser63 and Ser73, and c-Fos at Ser32. Knockdown of c-Jun and c-Fos with siRNAs substantially inhibited the expression of SphK1 and FN, whereas overexpression of c-Jun and c-Fos significantly increased the expression of SphK1 and FN. Curcumin treatment greatly decreased the levels of c-Jun, c-Fos, SphK1, and FN in the kidney tissues of diabetic rats. SiRNAs targeting SphK1 and S1P2 receptor respectively inhibited the phosphorylation of c-Jun (ser63 and ser73) and c-Fos (ser32), as well as FN expression under both normal and HG conditions. Our data demonstrated that the activated SphK1-S1P signaling pathway in GMCs under diabetic conditions is closely associated with AP-1 to form a positive feedback loop. This positive feedback loop functions as an important molecular basis for the sustained activation of SphK1-S1P pathway and increased FN expression that lead to the initiation and progression of DN.

Topics: Animals; Binding Sites; Cells, Cultured; Curcumin; Diabetes Mellitus; Diabetic Nephropathies; DNA-Binding Proteins; Enzyme Inhibitors; Fibronectins; Glucose; JNK Mitogen-Activated Protein Kinases; Lysophospholipids; Male; Mesangial Cells; Phosphorylation; Phosphotransferases (Alcohol Group Acceptor); Promoter Regions, Genetic; Protein Binding; Proto-Oncogene Proteins c-fos; Rats; Receptors, Lysosphingolipid; RNA Interference; RNA, Small Interfering; Signal Transduction; Sphingosine; Sweetening Agents; Transcription Factor AP-1

Turmeric (Curcuma longa) is a rhizomatous herbaceous perennial plant of the ginger family which has been used to treat biliary disorders, anorexia, cough, rheumatism, cancer, sinusitis, hepatic disorders, hyperglycemia, obesity, and diabetes in both Ayurvedic and Traditional Chinese Medicine. Suggested mechanisms of action include the modulation of signal transduction cascades and effects on gene expression, however they remain to be elucidated. In this study, the expression of some proteins responsible for transcription factors, inflammation, and metabolic control were evaluated by western blot in 15-week-old db/db mice livers treated with curcumin 0.75% mixed in their diet for 8 weeks. In addition, nitrosative stress was evaluated. Curcumin increased the expression of AMPK and PPARγ, and diminished NF-κB protein in db/db mice. However, it did not modify the expression of PGC-1α or SIRT1. Nitrosative stress present in db/db mice livers was determined by a unique nitrotyrosylated protein band (75 kDa) and was not reverted with curcumin. In conclusion, curcumin regulates the expression of AMPK, PPARγ, and NF-κB; suggesting a beneficial effect for treatment of T2DM complications. In order to observe best beneficial effects it is desirable to administer curcumin in the earlier states of T2DM.

Topics: AMP-Activated Protein Kinases; Animals; Curcumin; Diabetes Mellitus; Liver; Male; Mice; NF-kappa B; PPAR gamma

Polyphenols are largely studied for their beneficial action in various pathologies, but the correlation with their effects on cell membranes is still elusive. In the present study we assessed the effects exerted in vitro by quercetin, epigallocatechin gallate and curcumin on membrane fluidity and transmembrane potential of human umbilical vein endothelial cells and Jurkat T lymphoblasts, in experimental conditions mimicking diabetes mellitus, i.e. high glucose conditions or increased concentration of advanced glycation end products. Results showed that the investigated polyphenols had beneficial effects on cell membranes altered in diabetic conditions, by restoring transmembrane potential and by membrane "stiffening". Moreover, they limited the release of pro-inflammatory factors, like monocyte chemotactic protein-1. These effects were more obvious for cells exposed to advanced glycation end products specific for the late stages of diabetes. Apparently, the inhibitory action of polyphenols on lipid peroxidation was associated with a decrease of membrane fluidity. Concluding, our in vitro study highlighted the potential beneficial action of polyphenols mainly in the late stages of diabetes, exerted at the level of membrane fluidity and transmembrane potential, accompanied by an anti-inflammatory effect on endothelial and immune cells.

Topics: Anisotropy; Antioxidants; Catechin; Cell Membrane; Cell Survival; Chemokine CCL2; Curcumin; Diabetes Mellitus; Human Umbilical Vein Endothelial Cells; Humans; Jurkat Cells; Lipid Peroxidation; Membrane Potentials; Quercetin

We investigated the effect of curcumin on insulin resistance and glucose homeostasis in male C57BL/KsJ-db/db mice and their age-matched lean non-diabetic db/+ mice. Both db/+ and db/db mice were fed with or without curcumin (0.02%, wt/wt) for 6 wks. Curcumin significantly lowered blood glucose and HbA 1c levels, and it suppressed body weight loss in db/db mice. Curcumin improved homeostasis model assessment of insulin resistance and glucose tolerance, and elevated the plasma insulin level in db/db mice. Hepatic glucokinase activity was significantly higher in the curcumin-supplemented db/db group than in the db/db group, whereas glucose-6-phosphatase and phosphoenolpyruvate carboxykinase activities were significantly lower. In db/db mice, curcumin significantly lowered the hepatic activities of fatty acid synthase, beta-oxidation, 3-hydroxy-3-methylglutaryl coenzyme reductase, and acyl-CoA: cholesterol acyltransferase. Curcumin significantly lowered plasma free fatty acid, cholesterol, and triglyceride concentrations and increased the hepatic glycogen and skeletal muscle lipoprotein lipase in db/db mice. Curcumin normalized erythrocyte and hepatic antioxidant enzyme activities (superoxide dismutase, catalase, gluthathione peroxidase) in db/db mice that resulted in a significant reduction in lipid peroxidation. However, curcumin showed no effect on the blood glucose, plasma insulin, and glucose regulating enzyme activities in db/+ mice. These results suggest that curcumin seemed to be a potential glucose-lowering agent and antioxidant in type 2 diabetic db/db mice, but had no affect in non-diabetic db/+ mice.

Topics: Adipose Tissue; Animals; Blood Glucose; Curcumin; Diabetes Mellitus; Dietary Supplements; Glucose; Glucose Tolerance Test; Glycated Hemoglobin; Homeostasis; Insulin; Insulin Resistance; Lipoprotein Lipase; Male; Mice; Mice, Inbred C57BL; Mice, Inbred Strains; Muscle, Skeletal

The turmeric (Curcuma longa L. rhizomes) EtOH extract significantly suppressed an increase in blood glucose level in type 2 diabetic KK-A(y) mice. In an in vitro evaluation, the extract stimulated human adipocyte differentiation in a dose-dependent manner and showed human peroxisome proliferator-activated receptor (PPAR)-gamma ligand-binding activity in a GAL4-PPAR-gamma chimera assay. The main constituents of the extract were identified as curcumin, demethoxycurcumin, bisdemethoxycurcumin, and ar-turmerone, which had also PPAR-gamma ligand-binding activity. These results indicate that turmeric is a promising ingredient of functional food for the prevention and/or amelioration of type 2 diabetes and that curcumin, demethoxycurcumin, bisdemethoxycurcumin, and ar-turmerone mainly contribute to the effects via PPAR-gamma activation.

Topics: Animals; Curcuma; Diabetes Mellitus; Dose-Response Relationship, Drug; Female; Hypoglycemic Agents; Mice; Rhizome

There is evidence for increased levels of circulating reactive oxygen species (ROS) in diabetics, as indirectly inferred by the findings of increased lipid peroxidation and decreased antioxidant status. Direct measurements of intracellular generation of ROS using fluorescent dyes also demonstrate an association of oxidative stress with diabetes. Although phenolic compounds attenuate oxidative stress-related tissue damage, there are concerns over toxicity of synthetic phenolic antioxidants and this has considerably stimulated interest in investigating the role of natural phenolics in medicinal applications. Curcumin (the primary active principle in turmeric, Curcuma longa Linn.) has been claimed to represent a potential antioxidant and antiinflammatory agent with phytonutrient and bioprotective properties. However there are lack of molecular studies to demonstrate its cellular action and potential molecular targets. In this study the antioxidant effect of curcumin as a function of changes in cellular ROS generation was tested. Our results clearly demonstrate that curcumin abolished both phorbol-12 myristate-13 acetate (PMA) and thapsigargin-induced ROS generation in cells from control and diabetic subjects. The pattern of these ROS inhibitory effects as a function of dose-dependency suggests that curcumin mechanistically interferes with protein kinase C (PKC) and calcium regulation. Simultaneous measurements of ROS and Ca2+ influx suggest that a rise in cytosolic Ca2+ may be a trigger for increased ROS generation. We suggest that the antioxidant and antiangeogenic actions of curcumin, as a mechanism of inhibition of Ca2+ entry and PKC activity, should be further exploited to develop suitable and novel drugs for the treatment of diabetic retinopathy and other diabetic complications.

Topics: Calcium; Case-Control Studies; Curcumin; Diabetes Mellitus; Humans; Protein Kinase C; Reactive Oxygen Species; Tetradecanoylphorbol Acetate