Peoniflorin Preconditioning Protects Against Myocardial Ischemia/Reperfusion Injury Through Inhibiting Myocardial Apoptosis: RISK Pathway Involved

Preconditioning with Peoniflorin, a component of traditional Chinese prescriptions, was proposed to be a potential strategy for cardioprotection against ischemia/reperfusion (I/R) injury. However, the cardioprotective effect of Peoniflorin preconditioning has not been thoroughly confirmed, and the underlying mechanism remains unclear. Here, we examined the cardioprotective effect and its mechanism of Peoniflorin preconditioning against myocardial I/R injury. Rats were subjected to 30 min of transient ischemia followed by 2 h of reperfusion with or without Peoniflorin (100 mg/kg) prior to reperfusion. Peoniflorin preconditioning significantly limited myocardial infarct size and reperfusion arrhythmias, as well as obviously attenuated the histomorphological and micromorphological damages induced by I/R injury. The reduced myocardial injury was also associated with the anti-apoptotic effect of Peoniflorin, as evidence by decreased TUNEL-positive cells, upregulation of BCL-2 expression, and downregulation of Bax and caspase-3 expression. In an effort to evaluate the mechanism responsible for the observed cardioprotective and anti-apoptotic effect, Western blot of phosphorylated protein was performed after 20 min of reperfusion. Results showed that Peoniflorin preconditioning activated both the Akt and ERK1/2 arm of the reperfusion injury salvage kinase (RISK) pathway. To further confirm this mechanism, the PI3K signaling inhibitor LY294002 and ERK1/2 signaling inhibitor PD98059 were administered in vivo. The cardioprotective and anti-apoptotic effects of Peoniflorin preconditioning were diminished but not abolished by pretreatment with LY294002 or PD98059. Taken together, these results indicate that Peoniflorin preconditioning protects the myocardial against I/R injury and inhibits myocardial apoptosis via the activation of the RISK pathway, highlighting the potential therapeutic effects of Peoniflorin on reducing myocardial I/R injury.