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.