chrysin and Diabetes-Mellitus--Type-2

Cardiometabolic diseases (CMD) have caused a great burden in terms of morbidity and mortality worldwide. The vicious cycle of CMD consists of type II diabetes, hypertension, dyslipidemia, obesity, and atherosclerosis. They have interlinked pathways, interacting and interconnecting with each other. The natural flavonoid chrysin has been shown to possess a broad spectrum of therapeutic activities for human health. Herein, we did an in-depth investigation of the novel mechanisms of chrysin's cardioprotection against cardiometabolic disorders. Studies have shown that chrysin protects the cardiovascular system by enhancing the intrinsic antioxidative defense system. This antioxidant property enhanced by chrysin protects against several risk factors of cardiometabolic disorders, including atherosclerosis, vascular inflammation and dysfunction, platelet aggregation, hypertension, dyslipidemia, cardiotoxicity, myocardial infarction, injury, and remodeling, diabetes-induced injuries, and obesity. Chrysin also exhibited anti-inflammatory mechanisms through inhibiting pro-inflammatory pathways, including NF-κB, MAPK, and PI3k/Akt. Furthermore, chrysin modulated NO, RAS, AGE/RAGE, and PPARs pathways which contributed to the risk factors of cardiometabolic disorders. Taken together, the mechanisms in which chrysin protects against cardiometabolic disorder are more than merely antioxidation and anti-inflammation in the cardiovascular system.

Topics: Anti-Inflammatory Agents; Antioxidants; Atherosclerosis; Cardiotoxicity; Diabetes Mellitus, Type 2; Flavonoids; Humans; Hypertension; Obesity; Phosphatidylinositol 3-Kinases

Islet amyloid polypeptide (amylin), consecrated by the pancreatic β-cells with insulin, has a significant role to play in maintaining homeostasis of islet cell hormones. Alzheimer's disease is the predominant source of dementia. However, its etiology remains uncertain; it appears that type 2 diabetes mellitus and other prediabetic states of insulin resistance contribute to the intermittent Alzheimer's disease presence. Amylin is abnormally elevated in Type II diabetes patients, accumulated into amylin aggregates, and ultimately causes apoptosis of the β-cells, and till date, its mechanism remains unclear. Several flavonoids have inhibitory effects on amylin amyloidosis, but its inhibition mechanisms are unknown. Screening a collection of traditional compounds revealed the flavone Chrysin, a potential lead compound. Chrysin inhibits amyloid aggregate formation according to Thioflavin T binding, turbidimetry assay. We report results of molecular interaction analysis of Chrysin with amylin which shows potent binding affinity against amylin. Pharmacokinetics and Drug likeness studies of Chrysin also suggest that it is a potential lead compound. Therefore, Chrysin prevented amylin aggregation.

Topics: Alzheimer Disease; Animals; Apoptosis; Cell Line, Tumor; Diabetes Mellitus, Type 2; Flavonoids; Humans; Insulin-Secreting Cells; Islet Amyloid Polypeptide; Molecular Docking Simulation; Protein Aggregation, Pathological; Protein Binding; Rats

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Topics: Antioxidants; Diabetes Mellitus, Type 2; Enzyme Inhibitors; Fermentation; Flavonoids; Fruit; Fruit and Vegetable Juices; Gallic Acid; Lactobacillus plantarum; Malvales; Phenols; Probiotics

Advanced glycation end products (AGEs) play a causative role in the development of diabetic nephropathy via induction of matrix protein deposition in kidneys. This study investigated inhibitory effects of chrysin, present in bee propolis and herbs, on glomerulosclerosis in db/db mice and AGEs-exposed renal mesangial cells. The in vivo study explored the demoting effects of 10 mg/kg chrysin on glomerular fibrosis in a type 2 diabetic model. Oral supplementation of chrysin inhibited the collagen fiber accumulation and α-smooth muscle actin (α-SMA) induction in periodic acid schiff-positive renal tissues of db/db mice. Moreover, treating db/db mice with chrysin diminished the level of AGEs increased in diabetic glomeruli. The in vitro study employed human mesangial cells exposed to 100 μg/mL AGE-BSA for 72 h in the presence of 1⁻20 μM chrysin. Glucose increased mesangial AGE production via induction of receptor for AGEs. Chrysin suppressed the induction of collagens, α-SMA, fibroblast-specific protein-1 and matrix metalloproteinases enhanced by AGE-bovine serum albumin. Furthermore, chrysin blunted transforming growth factor-β1 induction and Smad 2/3 activation in AGEs-exposed mesangial cells. These results demonstrate that chrysin attenuated accumulation of myofibroblast-like cells and matrix proteins in AGEs-laden diabetic glomeruli. Therefore, chrysin may be a potential renoprotective agent targeting glucose-mediated AGEs-associated glomerulosclerosis and fibrosis.

Topics: Animals; Blood Glucose; Cells, Cultured; Cytoprotection; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Disease Models, Animal; Dose-Response Relationship, Drug; Extracellular Matrix; Fibrosis; Flavonoids; Glucose; Glycation End Products, Advanced; Humans; Mesangial Cells; Mice, Inbred C57BL; Receptor for Advanced Glycation End Products; Serum Albumin, Bovine; Signal Transduction; Smad Proteins, Receptor-Regulated; Transforming Growth Factor beta

Diabetic nepropathy (DN) is considered as the leading cause of end-stage renal disease (ESRD) worldwide, but the current available treatments are limited. Recent experimental evidences support the role of chronic microinflammation in the development of DN. Therefore, the tumor necrosis factor-alpha (TNF-α) pathway has emerged as a new therapeutic target for the treatment of DN. We investigated the nephroprotective effects of chrysin (5, 7-dihydroxyflavone) in a high fat diet/streptozotocin (HFD/STZ)-induced type 2 diabetic Wistar albino rat model. Chrysin is a potent anti-inflammatory compound that is abundantly found in plant extracts, honey and bee propolis. The treatment with chrysin for 16weeks post induction of diabetes significantly abrogated renal dysfunction and oxidative stress. Chrysin treatment considerably reduced renal TNF-α expression and inhibited the nuclear transcription factor-kappa B (NF-кB) activation. Furthermore, chrysin treatment improved renal pathology and suppressed transforming growth factor-beta (TGF-β), fibronectin and collagen-IV protein expressions in renal tissues. Chrysin also significantly reduced the serum levels of pro-inflammatory cytokines, interleukin-1beta (IL-1β) and IL-6. Moreover, there were no appreciable differences in fasting blood glucose and serum insulin levels between the chrysin treated groups compared to the HFD/STZ-treated group. Hence, our results suggest that chrysin prevents the development of DN in HFD/STZ-induced type 2 diabetic rats through anti-inflammatory effects in the kidney by specifically targeting the TNF-α pathway.

Topics: Animals; Anti-Inflammatory Agents; Blood Glucose; Blotting, Western; Cytokines; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Flavonoids; Insulin; Kidney; Kidney Function Tests; Male; Oxidative Stress; Rats; Rats, Wistar; Tumor Necrosis Factor-alpha