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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.
AuthorsJialin Duan, Ying Yin, Guo Wei, Jia Cui, Enhu Zhang, Yue Guan, Jiajia Yan, Chao Guo, Yanrong Zhu, Fei Mu, Yan Weng, Yanhua Wang, Xiaoxiao Wu, Miaomiao Xi, Aidong Wen
JournalScientific reports (Sci Rep) Vol. 5 Pg. 18123 (Dec 09 2015) ISSN: 2045-2322 [Electronic] England
PMID26648253 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Cardiotonic Agents
  • Reactive Oxygen Species
  • Saponins
  • chikusetsu saponin IVa
  • Oleanolic Acid
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3
  • Sirtuin 1
  • Glucose
  • Calcium
Topics
  • Animals
  • Apoptosis (drug effects)
  • Calcium (metabolism)
  • Cardiotonic Agents (pharmacology)
  • Cardiotoxicity
  • Glucose (metabolism, toxicity)
  • Male
  • Mice
  • Mitogen-Activated Protein Kinase 1 (metabolism)
  • Mitogen-Activated Protein Kinase 3 (metabolism)
  • Myoblasts, Cardiac (drug effects, metabolism)
  • Myocytes, Cardiac (drug effects, metabolism)
  • Oleanolic Acid (analogs & derivatives, pharmacology)
  • Oxidative Stress (drug effects)
  • Rats
  • Reactive Oxygen Species (metabolism)
  • Saponins (pharmacology)
  • Signal Transduction (drug effects)
  • Sirtuin 1 (metabolism)

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