Punicalagin Pretreatment Attenuates Myocardial Ischemia-Reperfusion Injury via Activation of AMPK

Punicalagin (PUN), a major bioactive component in pomegranate juice, has been proven to exert neuroprotective effects against cerebral ischemia/reperfusion (I/R) insult via anti-oxidant properties. This study aims to investigate whether PUN provides cardioprotection against myocardial I/R (MI/R) injury and the underlying mechanisms. PUN (30 mg/kg/d) or vehicle was intragastrically administered to Sprague-Dawley rats for one week before the operation. MI/R was induced by ligating the left anterior descending coronary artery for 30 min and subsequent reperfusion for 3 h. PUN pretreatment conferred cardioprotective effects against MI/R injury by improving cardiac function, limiting infarct size, reducing serum creatine kinase-MB and lactate activities, and suppressing cardiomyocyte apoptosis. Moreover, PUN pretreatment inhibited I/R-induced myocardial oxidative stress as evidenced by decreased generation of superoxide content and malonaldialdehyde formation and increased antioxidant capability. Furthermore, PUN pretreatment increased adenosine monophosphate-activated protein kinase (AMPK) and acetyl CoA carboxylase (ACC) phosphorylation in I/R hearts. AMPK inhibitor compound c inhibited PUN-enhanced AMPK phosphorylation, and blunted PUN-mediated anti-oxidative effects and cardioprotection. These results indicate for the first time that PUN pretreatment protect against I/R-induced oxidative stress and myocardial injury via activation of AMPK.