title: Chikusetsu saponin IVa confers cardioprotection via SIRT1/ERK1/2 and Homer1a pathway.
abstract: Hyperglycemia-induced reactive oxygen species (ROS) generation and Ca(2+) overload contribute to the development of diabetic cardiomyopathy. In this study, we aimed to study the protective effects of Chikusetsu saponin IVa (CHS) from Aralia taibaiensis against hyperglycemia-induced myocardial injuries. Treatment of H9c2 cells with high glucose (HG) for 24 h resulted in a loss of cell viability and increase of ROS, LDH and Ca(2+) levels, and also induced cell apoptosis, and those changes were all markedly reversed by the administration of CHS. In further studies, CHS dose-dependently increased the expression of Homer1a, ERK1/2 and SIRT1 in both H9c2 cells and rat primary cardiomyocytes. However, transfection of Homer1a-specific siRNA abolished the ability of CHS in controlling the ROS and Ca(2+) homeostasis. Moreover, specific SIRT1 inhibitors or siRNA significantly suppressed the enhanced phosphorylation of ERK1/2 and expression of Homer1a induced by CHS as well as its cytoprotective effect. CHS induced Homer1a expression was also suppressed by siERK1/2. Additionally, results in diabetic mice also showed that CHS protected myocardium from I/R-introduced apoptosis by activating the SIRT1/ERK1/2/Homer1a pathway. These results demonstrated that CHS protected against hyperglycemia-induced myocardial injury through SIRT1/ERK1/2 and Homer1a pathway in vivo and in vitro.
authors.affiliation: Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, China.
authors.forename: Jialin
authors.initials: J
authors.lastname: Duan
authors.affiliation: Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Yin
authors.affiliation: Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, China.
authors.forename: Guo
authors.initials: G
authors.lastname: Wei
authors.affiliation: Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Cui
authors.affiliation: College of Pharmacy, Shaanxi University of Chinese Medicine, XianYang 712083, PR China.
authors.forename: Enhu
authors.initials: E
authors.lastname: Zhang
authors.affiliation: Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Guan
authors.affiliation: Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, China.
authors.forename: Jiajia
authors.initials: J
authors.lastname: Yan
authors.affiliation: Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Guo
authors.affiliation: Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, China.
authors.forename: Yanrong
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Mu
authors.affiliation: Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Weng
authors.affiliation: Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, China.
authors.forename: Yanhua
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, China.
authors.forename: Xiaoxiao
authors.initials: X
authors.lastname: Wu
authors.affiliation: Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, China.
authors.forename: Miaomiao
authors.initials: M
authors.lastname: Xi
authors.affiliation: Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, China.
authors.forename: Aidong
authors.initials: A
authors.lastname: Wen
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D002316:Cardiotonic Agents / Q000494:pharmacology*; D066126:Cardiotoxicity; D005947:Glucose / Q000378:metabolism / Q000633:toxicity; D008297:Male; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D032386:Myoblasts, Cardiac / Q000187:drug effects / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism; D009828:Oleanolic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D012503:Saponins / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects*; D056564:Sirtuin 1 / Q000378:metabolism*
chemical_list: D002316:Cardiotonic Agents; D017382:Reactive Oxygen Species; D012503:Saponins; C098580:chikusetsu saponin IVa; D009828:Oleanolic Acid; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D056564:Sirtuin 1; D005947:Glucose; D002118:Calcium