Yingda Feng1, Yunyang Lu2, Dan Liu3, Wei Zhang4, Juntian Liu5, Haifeng Tang6, Yanrong Zhu7. 1. Institute of Materia Medica, School of Pharmacy, Fourth Military Medical University, Xi'an, Shaanxi 710032, China; Department of Ultrasound, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, China. 2. Institute of Materia Medica, School of Pharmacy, Fourth Military Medical University, Xi'an, Shaanxi 710032, China. 3. Department of Pharmacy, 210 Hospital of PLA, Dalian, Liaoning 116021, China. 4. Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, China. 5. Department of Pharmacology, Xi'an Jiaotong University School of Medicine, Xi'an, Shaanxi 710061, China. 6. Institute of Materia Medica, School of Pharmacy, Fourth Military Medical University, Xi'an, Shaanxi 710032, China. Electronic address: tanghaifeng71@163.com. 7. Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, China; Department of Pharmacology, Xi'an Jiaotong University School of Medicine, Xi'an, Shaanxi 710061, China. Electronic address: zyr19830812@163.com.
Abstract
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.
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.