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San-Huang-Xie-Xin-Tang protects cardiomyocytes against hypoxia/reoxygenation injury via inhibition of oxidative stress-induced apoptosis.

Abstract
Oxidative stress has been widely implicated in the pathogenesis of hypoxia/reoxygenation (H/R) injury. San-Huang-Xie-Xin-Tang (SHXT), a widely used traditional Chinese medication, has been shown to possess antioxidant effects. Here, we investigated whether SHXT and its main component baicalin can attenuate oxidative stress induced by H/R injury. H9c2 rat ventricular cells were exposed to SHXT or baicalin followed by hypoxia for 24 h and/or reoxygenation for 8 h. Pretreatment with SHXT and baicalin both significantly prevented cell death and production of reactive oxygen species induced by hypoxia or H/R in H9c2 cardiomyoctes. In addition, SHXT and baicalin also inhibited hypoxia- or H/R-induced apoptosis, with associated decreased Bax protein, increased Bcl-2 protein, and decreased caspase-3 activity. Furthermore, we found that hypoxia and H/R decreased endothelial nitric oxide synthase (eNOS) expression and nitrite production, and these effects were counteracted by SHXT and baicalein. Finally, SHXT inhibited H/R-induced activation of p38 mitogen activated protein kinase (MAPK) and c-Jun N-terminal kinase (JNK) phosphorylation in H9c2 rat ventricular cells. The present study demonstrates for the first time that SHXT can protect cardiomyocytes from H/R injury via inhibition of oxidative stress-induced apoptosis. These cardioprotective effects are possibly mediated through eNOS enhancement and p38 MAPK and JNK-dependent signaling pathways.
AuthorsShu-Fen Liou, Jong-Hau Hsu, Jyh-Chong Liang, Hung-Jen Ke, Ing-Jun Chen, Jiunn-Ren Wu, Jwu-Lai Yeh
JournalJournal of natural medicines (J Nat Med) Vol. 66 Issue 2 Pg. 311-20 (Apr 2012) ISSN: 1861-0293 [Electronic] Japan
PMID21979292 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Drugs, Chinese Herbal
  • Nitrites
  • Reactive Oxygen Species
  • San-Huang-Xie-Xin-Tang
Topics
  • Animals
  • Apoptosis (drug effects)
  • Blotting, Western
  • Cell Hypoxia (physiology)
  • Cell Line
  • Cell Survival (drug effects)
  • Drugs, Chinese Herbal (pharmacology)
  • Myocytes, Cardiac (drug effects, metabolism)
  • Nitrites (metabolism)
  • Oxidative Stress (drug effects)
  • Rats
  • Reactive Oxygen Species (metabolism)
  • Reperfusion Injury (prevention & control)

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