Taxifolin prevents diabetic cardiomyopathy in vivo and in vitro by inhibition of oxidative stress and cell apoptosis

• Published in: Food and chemical toxicology Vol. 63; pp. 221 - 232
• Main Authors: Sun, Xiao, Chen, Rong-chang, Yang, Zhi-hong, Sun, Gui-bo, Wang, Min, Ma, Xiao-jun, Yang, Li-juan, Sun, Xiao-bo
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 01.01.2014; Elsevier
• Subjects: angiotensin II; Angiotensin II - blood; animal disease models; Animals; Apoptosis; Apoptosis - drug effects; Biological and medical sciences; cardiac output; Cardiology. Vascular system; cardiomyocytes; cardiomyopathy; cardioprotective effect; caspase-3; caspase-9; Caspases - metabolism; Cell Line; cytochrome c; diabetes; Diabetes Mellitus, Experimental - complications; Diabetes. Impaired glucose tolerance; Diabetic Cardiomyopathies - prevention & control; Diabetic cardiomyopathy; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; enzyme activity; Enzyme-Linked Immunosorbent Assay; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Heart; heart failure; hyperglycemia; In Situ Nick-End Labeling; In Vitro Techniques; in vivo studies; Male; Medical sciences; membrane potential; Mice; Mice, Inbred C57BL; mitochondria; mitochondrial membrane; myoblasts; Myocarditis. Cardiomyopathies; NAD(P)H oxidase (H2O2-forming); NADP (coenzyme); NADPH oxidase; NADPH Oxidases - metabolism; Oxidative stress; Oxidative Stress - drug effects; patients; Quercetin - analogs & derivatives; Quercetin - pharmacology; Rats; Reactive Oxygen Species - metabolism; Streptozocin; Taxifolin; Toxicology; EF; Oxidative stress; AST; GSH-Px; LVVs; RAS; CK-MB; SOD; MDA; FS; Ang II; DCM; LDH; ΔΨm; NADPH oxidase; ROS; CAT; STZ; Diabetic cardiomyopathy; Taxifolin; LVVd; AT1; Apoptosis; Endocrinopathy; Enzyme; Cardiomyopathy; Diabetes mellitus; Oxidase; Cardiovascular disease; Myocardial disease; Prevention; In vivo; Cell death; Heart disease; Oxidoreductases; Inhibition; LV end-systolic volume; rennin-angiotensin system; ejection fraction; reactive oxygen species; malondialdehyde; catalase; angiotensin receptor 1; ΔΨ(m); mitochondrial membrane potential; lactate dehydrogenase; LV end-diastolic volume; aspartate aminotransferase; streptozotocin; angiotensin II; superoxide dismutase; creatinine kinase-MB isoenzyme; fractional shortening; glutathione peroxidase
• ISSN: 0278-6915; 1873-6351; 1873-6351
• DOI: 10.1016/j.fct.2013.11.013

•Taxifolin improved diastolic dysfunction in streptozotocin-induced diabetic mice.•Taxifolin inhibited oxidative stress by enhancing antioxidative enzymes’ activities.•Taxifolin inhibited NADPH oxidase activities and reduced ROS level.•JAK/STAT pathway was involved in the protective effects of taxifolin. Diabetic cardiomyopathy has been increasingly recognized as an important cause of heart failure in diabetic patients. Excessive oxidative stress has been suggested to play a critical role in the development of diabetic cardiomyopathy. The objective of this study was to investigate the potential protective effects and mechanisms of taxifolin on cardiac function of streptozotocin-induced diabetic mice and on hyperglycemia-induced apoptosis of H9c2 cardiac myoblasts. In vivo study revealed that taxifolin improved diastolic dysfunction, ameliorated myocardium structure abnormality, inhibited myocyte apoptosis and enhanced endogenous antioxidant enzymes activities. Interestingly, taxifolin reduced angiotensin II level in myocardium, inhibited NADPH oxidase activity, and increased JAK/STAT3 activation. In vitro investigation demonstrated that taxifolin inhibited 33mM glucoseinduced H9c2 cells apoptosis by decreasing intracellular ROS level. It also inhibited caspase-3 and caspase-9 activation, restored mitochondrial membrane potential, and regulated the expression of proteins related to the intrinsic pathway of apoptosis, thus inhibiting the release of cytochrome c from mitochondria into the cytoplasm. In conclusion, taxifolin exerted cardioprotective effects against diabetic cardiomyopathy by inhibiting oxidative stress and cardiac myocyte apoptosis and might be a potential agent in the treatment of diabetic cardiomyopathy.