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

Abstract

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 33 mM 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.

Keywords: AST; AT1; Ang II; Apoptosis; CAT; CK-MB; DCM; Diabetic cardiomyopathy; EF; FS; GSH-Px; LDH; LV end-diastolic volume; LV end-systolic volume; LVVd; LVVs; MDA; NADPH oxidase; Oxidative stress; RAS; ROS; SOD; STZ; Taxifolin; angiotensin II; angiotensin receptor 1; aspartate aminotransferase; catalase; creatinine kinase-MB isoenzyme; diabetic cardiomyopathy; ejection fraction; fractional shortening; glutathione peroxidase; lactate dehydrogenase; malondialdehyde; mitochondrial membrane potential; reactive oxygen species; rennin-angiotensin system; streptozotocin; superoxide dismutase; ΔΨ(m).