title: Myricitrin Attenuates High Glucose-Induced Apoptosis through Activating Akt-Nrf2 Signaling in H9c2 Cardiomyocytes.
abstract: Hyperglycemia, as well as diabetes mellitus, has been shown to trigger cardiac cell apoptosis. We have previously demonstrated that myricitrin prevents endothelial cell apoptosis. However, whether myricitrin can attenuate H9c2 cell apoptosis remains unknown. In this study, we established an experiment model in H9c2 cells exposed to high glucose. We tested the hypothesis that myricitrin may inhibit high glucose (HG)-induced cardiac cell apoptosis as determined by TUNEL staining. Furthermore, myricitrin promoted antioxidative enzyme production, suppressed high glucose-induced reactive oxygen species (ROS) production and decreased mitochondrial membrane potential (MMP) in H9c2 cells. This agent significantly inhibited apoptotic protein expression, activated Akt and facilitated the transcription of NF-E2-related factor 2 (Nrf2)-mediated protein (heme oxygenase-1 (HO-1) and quinone oxidoreductase 1 (NQO-1) expression as determined by Western blotting. Significantly, an Akt inhibitor (LY294002) or HO-1 inhibitor (ZnPP) not only inhibited myricitrin-induced HO-1/NQO-1 upregulation but also alleviated its anti-apoptotic effects. In summary, these observations demonstrate that myricitrin activates Nrf2-mediated anti-oxidant signaling and attenuates H9c2 cell apoptosis induced by high glucose via activation of Akt signaling.
authors.affiliation: Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100193, China. zhangbin7@126.com.|Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Beijing 100193, China. zhangbin7@126.com.|Beijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, Beijing 100193, China. zhangbin7@126.com.|Key Laboratory of Efficacy Evaluation of Chinese Medicine against Glyeolipid Metabolism Disorder Disease, State Administration of Traditional Chinese Medicine, Beijing 100193, China. zhangbin7@126.com.
authors.forename: Bin
authors.initials: B
authors.lastname: Zhang
authors.affiliation: School of Life Science, Beijing Institute of Technology, Beijing 100081, China. Yp_chen@yeah.net.
authors.forename: Yaping
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Center of Research and Development on Life Sciences and Environmental Sciences, Harbin University of Commerce, Harbin 150076, China. jinqilinsq@163.com.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Shen
authors.affiliation: School of Life Science, Beijing Institute of Technology, Beijing 100081, China. gyliu@bit.edu.cn.
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. yejingxue2002@126.com.|Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Beijing 100193, China. yejingxue2002@126.com.|Beijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, Beijing 100193, China. yejingxue2002@126.com.|Key Laboratory of Efficacy Evaluation of Chinese Medicine against Glyeolipid Metabolism Disorder Disease, State Administration of Traditional Chinese Medicine, Beijing 100193, China. yejingxue2002@126.com.
authors.forename: Jingxue
authors.initials: J
authors.lastname: Ye
authors.affiliation: Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100193, China. sunguibo@126.com.|Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Beijing 100193, China. sunguibo@126.com.|Beijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, Beijing 100193, China. sunguibo@126.com.|Key Laboratory of Efficacy Evaluation of Chinese Medicine against Glyeolipid Metabolism Disorder Disease, State Administration of Traditional Chinese Medicine, Beijing 100193, China. sunguibo@126.com.
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. sunsubmit@163.com.|Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Beijing 100193, China. sunsubmit@163.com.|Beijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, Beijing 100193, China. sunsubmit@163.com.|Key Laboratory of Efficacy Evaluation of Chinese Medicine against Glyeolipid Metabolism Disorder Disease, State Administration of Traditional Chinese Medicine, Beijing 100193, China. sunsubmit@163.com.
authors.forename: Xiaobo
authors.initials: X
authors.lastname: Sun
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D005419:Flavonoids / Q000737:chemistry / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism* / Q000494:pharmacology; D051547:Heme Oxygenase-1 / Q000378:metabolism; D006943:Hyperglycemia / Q000378:metabolism*; D008929:Mitochondria, Heart / Q000187:drug effects / Q000378:metabolism; D008954:Models, Biological; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism*; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology; D010946:Plants, Medicinal / Q000737:chemistry; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000975:Antioxidants; D005419:Flavonoids; D051267:NF-E2-Related Factor 2; D010936:Plant Extracts; D017382:Reactive Oxygen Species; C008577:myricitrin; D051547:Heme Oxygenase-1; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D005947:Glucose
keywords: H9c2 cell; apoptosis; hyperglycemia; oxidative stress; reactive oxygen species