title: Myricitrin Alleviates Oxidative Stress-induced Inflammation and Apoptosis and Protects Mice against Diabetic Cardiomyopathy.
abstract: Diabetic cardiomyopathy (DCM) has been increasingly considered as a main cause of heart failure and death in diabetic patients. At present, no effective treatment exists to prevent its development. In the present study, we describe the potential protective effects and mechanisms of myricitrin (Myr) on the cardiac function of streptozotosin-induced diabetic mice and on advanced glycation end products (AGEs)-induced H9c2 cardiomyocytes. In vitro experiments revealed that pretreatment with Myr significantly decreased AGEs-induced inflammatory cytokine expression, limited an increase in ROS levels, and reduced cell apoptosis, fibrosis, and hypertrophy in H9c2 cells. These effects are correlated with Nrf2 activation and NF-κB inhibition. In vivo investigation demonstrated that oral administration of Myr at 300 mg/kg/day for 8 weeks remarkably decreased the expression of enzymes associated with cardiomyopathy, as well as the expression of inflammatory cytokines and apoptotic proteins. Finally, Myr improved diastolic dysfunction and attenuated histological abnormalities. Mechanistically, Myr attenuated diabetes-induced Nrf2 inhibition via the regulation of Akt and ERK phosphorylation in the diabetic heart. Collectively, these results strongly indicate that Myr exerts cardioprotective effects against DCM through the blockage of inflammation, oxidative stress, and apoptosis. This suggests that Myr might be a potential therapeutic agent for the treatment of DCM.
authors.affiliation: Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100193, China.|Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Beijing 100193, China.|Beijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, Beijing 100193, China.|Key Laboratory of efficacy evaluation of Chinese Medicine against glyeolipid metabolism disorder disease, State Administration of Traditional Chinese Medicine, Beijing 100193, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Center of Research and Development on Life Sciences and Environmental Sciences, Harbin University of Commerce, Harbin 150076, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Shen
authors.affiliation: School of Life Science, Beijing Institute of Technology, Beijing 100081, China.
authors.forename: Yaping
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100193, China.
authors.forename: Ruile
authors.initials: R
authors.lastname: Pan
authors.affiliation: Department of Animal Sciences, Purdue University, West Lafayette, IN 47907, USA.
authors.forename: Shihuan
authors.initials: S
authors.lastname: Kuang
authors.affiliation: School of Life Science, Beijing Institute of Technology, Beijing 100081, China.
authors.forename: Guiyan
authors.initials: G
authors.lastname: Liu
authors.affiliation: Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100193, China.|Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Beijing 100193, China.|Beijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, Beijing 100193, China.|Key Laboratory of efficacy evaluation of Chinese Medicine against glyeolipid metabolism disorder disease, State Administration of Traditional Chinese Medicine, Beijing 100193, China.
authors.forename: Guibo
authors.initials: G
authors.lastname: Sun
authors.affiliation: Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100193, China.|Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Beijing 100193, China.|Beijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, Beijing 100193, China.|Key Laboratory of efficacy evaluation of Chinese Medicine against glyeolipid metabolism disorder disease, State Administration of Traditional Chinese Medicine, Beijing 100193, China.
authors.forename: Xiaobo
authors.initials: X
authors.lastname: Sun
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002460:Cell Line; D058065:Diabetic Cardiomyopathies / Q000188:drug therapy* / Q000378:metabolism; D005419:Flavonoids / Q000494:pharmacology*; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects*
chemical_list: D005419:Flavonoids; C008577:myricitrin