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

Shu Fen Liou, Jong Hau Hsu, Jyh Chong Liang, Hung Jen Ke, Ing Jun Chen, Jiunn Ren Wu, Jwu Lai Yeh*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

39 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)311-320
Number of pages10
JournalJournal of Natural Medicines
Volume66
Issue number2
DOIs
Publication statusPublished - 2012 Apr
Externally publishedYes

Keywords

  • Apoptosis
  • Cardioprotection
  • eNOS
  • Hypoxia/reoxygenation
  • Reactive oxygen species
  • San-Huang-Xie-Xin-Tang

ASJC Scopus subject areas

  • Pharmaceutical Science
  • Drug Discovery
  • Complementary and alternative medicine
  • Organic Chemistry

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