title: YiQiFuMai Powder Injection Attenuates Ischemia/Reperfusion-Induced Myocardial Apoptosis Through AMPK Activation.
abstract: The YiQiFuMai powder injection (YQFM), a traditional Chinese medicine (TCM) prescription re-developed based on the well-known TCM formula Sheng-maisan, showed a wide range of pharmacological activities in cardiovascular diseases in clinics. However, its role in protection against myocardial ischemia/reperfusion (MI/R) injury has not been elucidated. The present study not only evaluated the cardioprotective effect of YQFM from MI/R injury but also investigated the potential molecular mechanisms both in vivo and in vitro. The myocardium infarct size, production of lactate dehydrogenase (LDH), creatine kinase (CK), cardiac function, TUNEL staining, and caspase-3 activity were measured. Cell viability was determined, and cell apoptosis was measured by Hoechst 33342 staining and flow cytometry. Mitochondrial membrane potential (ΔΨm) was measured, and ATP content was quantified by bioluminescent assay. Expression of apoptosis-related proteins, including Caspase-3, Bcl-2, Bax, AMPKα, and phospho-AMPKα, was analyzed by western blotting. AMPKα siRNA transfection was also applied to the mechanism elucidation. YQFM at a concentration of 1.06 g/kg significantly reduced myocardium infarct size and the production of LDH, CK in serum, improved the cardiac function, and also produced a significant decrease of apoptotic index. Further, combined treatment with compound C partly attenuated the anti-apoptotic effect of YQFM. In addition, pretreatment with YQFM ranging from 25 to 400 μg/mL markedly improved cell viability and decreased LDH release. Moreover, YQFM inhibited H9c2 apoptosis, blocked the expression of caspase-3, and modulated Bcl-2 and Bax proteins, leading to an increased mitochondrial membrane potential and cellular ATP content. Mechanistically, YQFM activated AMP-activated protein kinase (AMPK) signaling pathways whereas pretreatment with AMPK inhibitor Compound C and application of transfection with AMPKα siRNA attenuated the anti-apoptotic effect of YQFM. Our results indicated that YQFM could provide significant cardioprotection against MI/R injury, and potential mechanisms might suppress cardiomyocytes apoptosis, at least in part, through activating the AMPK signaling pathways.
authors.affiliation: Jiangsu Key Laboratory of TCM Evaluation and Translational Research, Department of Complex Prescription of TCM, China Pharmaceutical University , Nanjing, P.R. China .
authors.forename: Fang
authors.initials: F
authors.lastname: Li
authors.affiliation: Jiangsu Key Laboratory of TCM Evaluation and Translational Research, Department of Complex Prescription of TCM, China Pharmaceutical University , Nanjing, P.R. China .
authors.forename: Xianjie
authors.initials: X
authors.lastname: Zheng
authors.affiliation: Jiangsu Key Laboratory of TCM Evaluation and Translational Research, Department of Complex Prescription of TCM, China Pharmaceutical University , Nanjing, P.R. China .
authors.forename: Xiaoxue
authors.initials: X
authors.lastname: Fan
authors.affiliation: Jiangsu Key Laboratory of TCM Evaluation and Translational Research, Department of Complex Prescription of TCM, China Pharmaceutical University , Nanjing, P.R. China .
authors.forename: Kefeng
authors.initials: K
authors.lastname: Zhai
authors.affiliation: Jiangsu Key Laboratory of TCM Evaluation and Translational Research, Department of Complex Prescription of TCM, China Pharmaceutical University , Nanjing, P.R. China .
authors.forename: Yisha
authors.initials: Y
authors.lastname: Tan
authors.affiliation: Jiangsu Key Laboratory of TCM Evaluation and Translational Research, Department of Complex Prescription of TCM, China Pharmaceutical University , Nanjing, P.R. China .
authors.forename: Junping
authors.initials: J
authors.lastname: Kou
authors.affiliation: Jiangsu Key Laboratory of TCM Evaluation and Translational Research, Department of Complex Prescription of TCM, China Pharmaceutical University , Nanjing, P.R. China .
authors.forename: Boyang
authors.initials: B
authors.lastname: Yu
mesh_terms: D000263:Adenylate Kinase / Q000502:physiology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002478:Cells, Cultured; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D007267:Injections; D051379:Mice; D008813:Mice, Inbred ICR; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy* / Q000473:pathology; D009206:Myocardium / Q000473:pathology*; D011208:Powders; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D051028:bcl-2-Associated X Protein / Q000032:analysis
chemical_list: C494827:Bax protein, mouse; D004365:Drugs, Chinese Herbal; D011208:Powders; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; C584693:yi-qi-fu-mai; D000263:Adenylate Kinase
keywords: AMPK; YiQiFuMai powder injection; apoptosis; cardioprotection; myocardial ischemia/reperfusion