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.