title: San-Huang-Xie-Xin-Tang Prevents Rat Hearts from Ischemia/Reperfusion-Induced Apoptosis through eNOS and MAPK Pathways.
abstract: San-Huang-Xie-Xin-Tang (SHXT) is a traditional Chinese medication consisting of three herbs, namely Coptidis rhizome, Scutellariae radix and Rhei rhizome. This study aimed to examine the cardioprotective effects of SHXT in a rat model of acute myocardial apoptosis induced by ischemia/reperfusion (I/R). Vehicle (intravenous saline) or SHXT (intravenous or oral) was administered prior to I/R (occlusion of left coronary artery for 45 min followed by reperfusion for 2 h). In the vehicle group, myocardial I/R caused myocardial infarction with increased plasma cardiac enzymes, severe arrhythmia and mortality. Myocardial apoptosis was induced by I/R as evidenced by DNA ladder and Bcl-2/Bax ratio. In the SHXT group, we found that SHXT significantly reduced plasma levels of cardiac enzymes, arrhythmia scores (from 5 ± 1 to 2 ± 1, P < .01) and mortality rate (from 53 to 0%, P < .01). In addition, pretreatment with intravenous SHXT reduced the infarct size dose-dependently when compared with the vehicle group (10 mg kg(-1): 14.0 ± 0.2 versus 44.5 ± 5.0%, and 30 mg kg(-1): 6.2 ± 1.2% versus 44.5 ± 5.0%, both P < .01). Similarly, oral administration of SHXT reduced the infarct size dose-dependently. Furthermore, SHXT markedly decreased the apoptosis induced by I/R with increased Bcl-2/Bax ratio. Finally, we found that SHXT counteracted the I/R-induced downstream signaling, resulting in increased myocardial eNOS expression and plasma nitrite, and decreased activation of ERK1/2, p38 and JNK. These data suggest that SHXT has cardioprotective effects against I/R-induced apoptosis, and that these effects are mediated, at least in part, by eNOS and MAPK pathways.
authors.affiliation: Department of Pharmacy, Chia-Nan University of Pharmacy and Science, Tainan, Taiwan.
authors.forename: Shu-Fen
authors.initials: SF
authors.lastname: Liou
authors.forename: Hung-Jen
authors.initials: HJ
authors.lastname: Ke
authors.forename: Jong-Hau
authors.initials: JH
authors.lastname: Hsu
authors.forename: Jyh-Chong
authors.initials: JC
authors.lastname: Liang
authors.forename: Hung-Hong
authors.initials: HH
authors.lastname: Lin
authors.forename: Ing-Jun
authors.initials: IJ
authors.lastname: Chen
authors.forename: Jwu-Lai
authors.initials: JL
authors.lastname: Yeh