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Cardioprotective effect of Danshensu against myocardial ischemia/reperfusion injury and inhibits apoptosis of H9c2 cardiomyocytes via Akt and ERK1/2 phosphorylation.

Abstract
Danshensu, as the effective component of Salvia miltiorrhiza (Danshen), has been widely used in clinic for treatment of cardiovascular diseases in China. In the present study, we aimed to confirm the cardioprotective effect of Danshensu from myocardial ischemia/reperfusion (MI/R) injury in vivo, and investigate the potential molecular mechanisms against simulated ischemia/reperfusion (SI/R) induced cardiomyocytes apoptosis in vitro. The rat model of MI/R injury was induced by a transient vessel occlusion for 30 min and reperfusion for 3h, Danshensu significantly reduced myocardium infarct size and the production of creatine kinase-MB (CK-MB), cardiac troponin (cTnI) in serum. In vitro experiment, H9c2 cardiomyocytes were incubated with vehicle or ischemic buffer during hypoxia, and then it was reoxygenated with or without Danshensu. Danshensu markedly improved cell viability and decreased lactate dehydrogenase (LDH) release. We confirmed anti-apoptotic effect of Danshensu both by flow-cytometric analysis and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, and this effect was associated with the increase of Bcl-2/Bax ratio and the decrease of active caspase-3 expression. Western blot analysis also showed that Danshensu increased phosphorylation of Akt and extracellular signal-related kinase 1/2 (ERK1/2) in H9c2 cells, and the protective effects of Danshensu were partially inhibited by phosphatidylinositol 3'-kinase (PI3K) specific inhibitor wortmannin or ERK specific inhibitor U0126. Our results suggested that Danshensu could provide significant cardioprotection against MI/R injury, and the potential mechanisms might to suppression of cardiomyocytes apoptosis through activating the PI3K/Akt and ERK1/2 signaling pathways.
AuthorsYing Yin, Yue Guan, Jialin Duan, Guo Wei, Yanrong Zhu, Wei Quan, Chao Guo, Dan Zhou, Yanhua Wang, Miaomiao Xi, Aidong Wen
JournalEuropean journal of pharmacology (Eur J Pharmacol) Vol. 699 Issue 1-3 Pg. 219-26 (Jan 15 2013) ISSN: 1879-0712 [Electronic] Netherlands
PMID23200898 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2012 Elsevier B.V. All rights reserved.
Chemical References
  • Lactates
  • 3,4-dihydroxyphenyllactic acid
  • Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins c-akt
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3
Topics
  • Animals
  • Apoptosis (drug effects)
  • Blotting, Western
  • Cell Line
  • Flow Cytometry
  • In Situ Nick-End Labeling
  • Lactates (pharmacology)
  • Male
  • Mitogen-Activated Protein Kinase 1 (metabolism)
  • Mitogen-Activated Protein Kinase 3 (metabolism)
  • Myocardial Reperfusion Injury (drug therapy, physiopathology)
  • Myocytes, Cardiac (drug effects, pathology)
  • Phosphatidylinositol 3-Kinases (metabolism)
  • Phosphorylation (drug effects)
  • Proto-Oncogene Proteins c-akt (metabolism)
  • Rats
  • Rats, Sprague-Dawley
  • Signal Transduction (drug effects)

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