Taxifolin prevents diabetic cardiomyopathy in vivo and in vitro by inhibition of oxidative stress and cell apoptosis |
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| Affiliation: | 1. 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;2. Medical Functional Laboratory, Basic Medical Department, Beihua University, Jilin, China;1. Programa de pós-graduação em ciências farmacêuticas - PPGCF, Universidade do Vale do Itajaí, Itajaí, SC, Brazil;2. Dipartimento di Scienze Farmaceutiche, Università degli Studi di Perugia, UniPg, via del Liceo 1, Perugia, PG, Italy;1. Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), Harbin Medical University, Harbin 150081, China;2. Department of Endocrinology, the Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China;3. Hebei Yiling Pharmaceutical Research Institute, Shijiazhuang 050035, China;4. Institute of Cardiovascular Research, Harbin Medical University, Harbin 150081, China;1. Department of Respiratory and Critical Care Medicine, Haihe Clinical College of Tianjin Medical University, Tianjin, 300350, PR China;2. Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Hebei North University, Zhangjiakou, 075000, PR China;1. Department of Biotechnology, School of Biosciences, Periyar University, Salem, 636011 Tamilnadu, India;2. Harborview Research & Training Building, University of Washington, School of Medicine, Seattle, WA 98104, United States;3. Translational Research Lab, Department of Biotechnology, Bharathiar University, Coimbatore, 641046 Tamilnadu, India;4. Department of Biotechnology, Siddaganga Institute of Technology, Tumakuru, 5720103 Karnataka, India;1. Aureo Science Co., Ltd., Hokudai Business Spring, North 21, West 12, Kita-ku, Sapporo, Hokkaido, 001-0021, Japan;2. Aureo Co., Ltd., 54-1 Kazusakoito, Kimitsu, Chiba, 292-1149, Japan;3. Hokkaido University Research Center for Zoonosis Control, North 20, West 10, Kita-ku, Sapporo, Hokkaido, 001-0020, Japan |
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| 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. |
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| Keywords: | Diabetic cardiomyopathy Taxifolin Oxidative stress NADPH oxidase Apoptosis |
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