title: Berberine alleviates cardiac ischemia/reperfusion injury by inhibiting excessive autophagy in cardiomyocytes.
abstract: Ischemia/reperfusion (I/R)-induced autophagy increases the severity of cardiomyocyte injury. The aim of this study was to investigate the effects of berberine, a natural extract from Rhizoma coptidis, on the I/R-induced excessive autophagy in in vitro and in vivo models. Autophagy was increased both in H9c2 myocytes during hypoxia/reoxygenation (H/R) injury and in mouse hearts exposed to I/R. And the expression level of p-AMPK and p-mTORC2 (Ser2481) were increased during H/R period. In addition, the increased autophagy level was correlated with reduced cell survival in H9c2 myocytes and increased infarct size in mouse hearts. However, berberine treatment significantly enhanced the H/R-induced cell viability and reduced I/R-induced myocardial infarct size, which was accompanied by improved cardiac function. The beneficial effect of berberine is associated with inhibiting the cellular autophagy level, due to decreasing the expression level of autophagy-related proteins such as SIRT1, BNIP3, and Beclin-1. Furthermore, both the level of p-AMPK and p-mTORC2 (Ser2481) in H9c2 myocytes exposed to H/R were decreased by berberine. In summary, berberine protects myocytes during I/R injury through suppressing autophagy activation. Therefore, berberine may be a promising agent for treating I/R-induced cardiac myocyte injury.
authors.affiliation: Department of Cardiology, The key lab of cardiovascular disease of Wenzhou, The First Affiliated Hospital of WenZhou Medical University, 2 Fuxue Road, WenZhou, ZheJiang 325000, PR China.
authors.forename: Zhouqing
authors.initials: Z
authors.lastname: Huang
authors.affiliation: Department of Cardiology, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, 200011 PR China.
authors.forename: Zhihua
authors.initials: Z
authors.lastname: Han
authors.affiliation: Department of Cardiology, The key lab of cardiovascular disease of Wenzhou, The First Affiliated Hospital of WenZhou Medical University, 2 Fuxue Road, WenZhou, ZheJiang 325000, PR China.
authors.forename: Bozhi
authors.initials: B
authors.lastname: Ye
authors.affiliation: Department of Cardiology, The key lab of cardiovascular disease of Wenzhou, The First Affiliated Hospital of WenZhou Medical University, 2 Fuxue Road, WenZhou, ZheJiang 325000, PR China.
authors.forename: Zhenyu
authors.initials: Z
authors.lastname: Dai
authors.affiliation: Department of Cardiology, The key lab of cardiovascular disease of Wenzhou, The First Affiliated Hospital of WenZhou Medical University, 2 Fuxue Road, WenZhou, ZheJiang 325000, PR China.
authors.forename: Peiren
authors.initials: P
authors.lastname: Shan
authors.affiliation: Department of Emergency, The First Affiliated Hospital of WenZhou Medical University, 2 Fuxue Road, WenZhou, ZheJiang 325000, PR China.
authors.forename: Zhongqiu
authors.initials: Z
authors.lastname: Lu
authors.affiliation: Department of Cardiology, The key lab of cardiovascular disease of Wenzhou, The First Affiliated Hospital of WenZhou Medical University, 2 Fuxue Road, WenZhou, ZheJiang 325000, PR China.
authors.forename: Kezhi
authors.initials: K
authors.lastname: Dai
authors.affiliation: Department of Cardiology, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, 200011 PR China. Electronic address: changqianwang@hotmail.com.
authors.forename: Changqian
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Cardiology, The key lab of cardiovascular disease of Wenzhou, The First Affiliated Hospital of WenZhou Medical University, 2 Fuxue Road, WenZhou, ZheJiang 325000, PR China. Electronic address: weijianhuang69@126.com.
authors.forename: Weijian
authors.initials: W
authors.lastname: Huang
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001343:Autophagy / Q000187:drug effects*; D001599:Berberine / Q000494:pharmacology* / Q000627:therapeutic use; D002460:Cell Line; D019610:Cytoprotection / Q000187:drug effects*; D008297:Male; D000076225:Mechanistic Target of Rapamycin Complex 2; D051379:Mice; D008810:Mice, Inbred C57BL; D046912:Multiprotein Complexes / Q000378:metabolism; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D010766:Phosphorylation / Q000187:drug effects; D020127:Recovery of Function / Q000187:drug effects; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism
chemical_list: D046912:Multiprotein Complexes; D001599:Berberine; D000076225:Mechanistic Target of Rapamycin Complex 2; D058570:TOR Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases
keywords: AMPK; Autophagy; Berberine; Heart; Ischemia/reperfusion injury