| Objective:To explore the protective effect and mechanisms of asiatic acid(AA) on myocardial ischemiaâ€reperfusion injury(Iâ€R).Methods and Results:In this study, we investigated the cardioprotective effects and mechanisms of AA in Cardiac cells of newborn rat simulated by oxygenâ€glucose deprivation /reoxygenation(OGD/R) in vitro and a mice model of MI/R injury by ligation left anterior decending(LAD) coronary artery in vivo. We found that the mice displayed progressive left vetricular(LV) dilation, Cardiac function decline and significant infarction postâ€surgery. Pretreated with AA significantly ameliorated cardiac dysfunction and reduced infarct size. Furthermore AA inhibited ROSâ€induced oxidative stress and apoptosis in cardiac myocytes both in vitro and in vivo. AA also reduced the Bax/Bclâ€2 ratio, the release of cytochrome c, and the expression of cleaved caspaseâ€9 and â€3, as well as blocked the phosphorylation of p38,ERK1/2 and JNK both in vitro and in vivo.Conclusions: The protective mechanisms of AA in myocardial Iâ€R injury were found to be associated with the inhibition of ROSâ€induced cardiomyocyte apoptosis via blocking MAPK signals and mitochondriaâ€dependent caspase activation. |