title: 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.
authors.affiliation: Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Institute of Medicinal Plant Development (IMPLAD), Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Sun
authors.affiliation: Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Institute of Medicinal Plant Development (IMPLAD), Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
authors.forename: Rong-chang
authors.initials: RC
authors.lastname: Chen
authors.affiliation: Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Institute of Medicinal Plant Development (IMPLAD), Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
authors.forename: Zhi-hong
authors.initials: ZH
authors.lastname: Yang
authors.affiliation: Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Institute of Medicinal Plant Development (IMPLAD), Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
authors.forename: Gui-bo
authors.initials: GB
authors.lastname: Sun
authors.affiliation: Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Institute of Medicinal Plant Development (IMPLAD), Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
authors.forename: Min
authors.initials: M
authors.lastname: Wang
authors.affiliation: Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Institute of Medicinal Plant Development (IMPLAD), Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
authors.forename: Xiao-jun
authors.initials: XJ
authors.lastname: Ma
authors.affiliation: Medical Functional Laboratory, Basic Medical Department, Beihua University, Jilin, China.
authors.forename: Li-juan
authors.initials: LJ
authors.lastname: Yang
authors.affiliation: Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Institute of Medicinal Plant Development (IMPLAD), Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China. Electronic address: sunxiaobosubmit@163.com.
authors.forename: Xiao-bo
authors.initials: XB
authors.lastname: Sun
mesh_terms: D000804:Angiotensin II / Q000097:blood; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D020169:Caspases / Q000378:metabolism; D002460:Cell Line; D003921:Diabetes Mellitus, Experimental / Q000150:complications; D058065:Diabetic Cardiomyopathies / Q000517:prevention & control*; D004797:Enzyme-Linked Immunosorbent Assay; D020287:In Situ Nick-End Labeling; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D019255:NADPH Oxidases / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D011794:Quercetin / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D013311:Streptozocin
chemical_list: D017382:Reactive Oxygen Species; D000804:Angiotensin II; D013311:Streptozocin; D011794:Quercetin; C003377:taxifolin; D019255:NADPH Oxidases; D020169:Caspases
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)