Apigenin-7-O-β-d-(-6″-p-coumaroyl)-glucopyranoside pretreatment attenuates myocardial ischemia/reperfusion injury via activating AMPK signaling.

AIMS

Apigenin-7-O-β-d-(-6″-p-coumaroyl)-glucopyranoside (APG) was considered as the major active compound derived from Clematis tangutica. Though we have demonstrated that APG exerts cardioprotective effects, the mechanism of APG-mediated cardioprotection remains largely unknown. Numerous studies indicate that endoplasmic reticulum stress (ERS) is a vital injury factor in myocardial ischemia reperfusion (MI/R). In this study, we mainly investigated whether modulation of the ERS and AMPK were involved in the cardioprotective action of APG during MI/R injury.

MAIN METHODS

The perfused isolated rat heart or primary neonatal rat cardiomyocytes which exposed to APG with or else without the AMPK inhibitor Compound C was then subject to MI/R. After reperfusion, the degree of myocardial injury was assessed by using lactate dehydrogenase (LDH) release, creatine kinase (CK) release, histological examination, and TTC staining. The protein expressions of p-AMPK, AMPK, p-PERK, PERK, p-eIF2α, eIF2α, CHOP, Bax, Bcl2 and Cleaved Caspase 3 were analyzed by western blot. The cell viability was assessed by CCK-8 kit while apoptosis assessed by using TUNEL assay.

KEY FINDINGS

Pretreatment of APG significantly improved cardiac function and suppressed ERS through activating the AMPK signaling pathway, which could simultaneously improve cardiac function, alleviate myocardial injury, increase the cell viability and decrease apoptosis.

SIGNIFICANCE

To conclude, APG ameliorates MI/R injury by activating the AMPK signaling pathway and relieving endoplasmic reticulum stress. APG may be a natural product with pharmacological preconditioning activity, which could do us a favor to develop more novel therapy methods to against MI/R injury in the future.