title: 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.
authors: Department of Pharmacy, Chia-Nan University of Pharmacy and Science, 60 Erh-Jen Road, Section 1, Pao-Ann, Jen-Te, Tainan 717, Taiwan.
authors: Shu-Fen
authors: SF
authors: Liou
authors: Jong-Hau
authors: JH
authors: Hsu
authors: Jyh-Chong
authors: JC
authors: Liang
authors: Hung-Jen
authors: HJ
authors: Ke
authors: Ing-Jun
authors: IJ
authors: Chen
authors: Jiunn-Ren
authors: JR
authors: Wu
authors: Jwu-Lai
authors: JL
authors: Yeh
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D015687:Cell Hypoxia / Q000502:physiology; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects*; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism*; D009573:Nitrites / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015427:Reperfusion Injury / Q000517:prevention & control*
chemical_list: D004365:Drugs, Chinese Herbal; D009573:Nitrites; D017382:Reactive Oxygen Species; C501029:San-Huang-Xie-Xin-Tang