title: Berberine improves pressure overload-induced cardiac hypertrophy and dysfunction through enhanced autophagy.
abstract: Cardiac hypertrophy is a maladaptive change in response to pressure overload, and is also an important risk for developing heart failure. Berberine is known to have cardioprotective effects in patients with hypertension and in animal models of cardiac hypertrophy. In the current study, we observed that transverse aortic contraction (TAC) surgery induced a marked increase in heart size, the ratio of heart weight to body weight, cardiomyocyte apoptosis, myocardial fibrosis, and hypertrophic marker brain natriuretic peptide, all of which were effectively suppressed by berberine administration. In addition, berberine enhanced autophagy in hypertrophic hearts, which was accompanied by a decrease in heart size, cardiac apoptosis, and the attenuation of cardiac dysfunction. Furthermore, use of autophagy inhibitor 3-methyladenine (3-MA) blocked berberine-induced autophagy level, and abrogated the protection of berberine against heart hypertrophy, cardiac dysfunction, and apoptosis. Berberine ameliorated TAC-induced endoplasmic reticulum stress, which was also abolished by 3-MA. Moreover, berberine significantly inhibited the upstream signaling of autophagy, such as the mammalian target of rapamycin (mTOR), extracellular signal-regulated kinase (ERK1/2), and p38 mitogen-activated protein kinase (MAPK) phosphorylation. We conclude that berberine could attenuate left ventricular remodeling and cardiomyocyte apoptosis through an autophagy-dependent mechanism in a rat model of cardiac hypertrophy, which is, at least in part, associated with enhanced autophagy through inhibition of mTOR, p38 and ERK1/2 MAPK signaling pathways.
authors: Division of Cardiovascular Medicine, Department of Medicine, Nanjing First Hospital, Nanjing Medical University, 68 Changle Road, Nanjing, China.
authors: Ming-Hui
authors: MH
authors: Li
authors: Division of Cardiovascular Medicine, Department of Medicine, Nanjing First Hospital, Nanjing Medical University, 68 Changle Road, Nanjing, China.
authors: Yao-Jun
authors: YJ
authors: Zhang
authors: Division of Cardiovascular Medicine, Department of Medicine, Nanjing First Hospital, Nanjing Medical University, 68 Changle Road, Nanjing, China.
authors: Yi-Hui
authors: YH
authors: Yu
authors: Division of Cardiovascular Medicine, Department of Medicine, Nanjing First Hospital, Nanjing Medical University, 68 Changle Road, Nanjing, China.
authors: Shao-Hua
authors: SH
authors: Yang
authors: Department of Cardiovascular Science, University of Sheffield, UK.
authors: Javaid
authors: J
authors: Iqbal
authors: Central Laboratory, General Clinical Research Center, Nanjing First Hospital, Nanjing Medical University, Nanjing, China.
authors: Qiong-Yu
authors: QY
authors: Mi
authors: Division of Cardiovascular Medicine, Department of Medicine, Nanjing First Hospital, Nanjing Medical University, 68 Changle Road, Nanjing, China.
authors: Bing
authors: B
authors: Li
authors: Division of Cardiovascular Medicine, Department of Medicine, Nanjing First Hospital, Nanjing Medical University, 68 Changle Road, Nanjing, China.
authors: Zhi-Mei
authors: ZM
authors: Wang
authors: Division of Cardiovascular Medicine, Department of Medicine, Nanjing First Hospital, Nanjing Medical University, 68 Changle Road, Nanjing, China.
authors: Wen-Xing
authors: WX
authors: Mao
authors: Central Laboratory, General Clinical Research Center, Nanjing First Hospital, Nanjing Medical University, Nanjing, China; Department of Pharmacology, Nanjing Medical University School of Pharmacy, Nanjing, China.
authors: Hong-Guang
authors: HG
authors: Xie
authors: Division of Cardiovascular Medicine, Department of Medicine, Nanjing First Hospital, Nanjing Medical University, 68 Changle Road, Nanjing, China. Electronic address: chmengx126@gmail.com.
authors: Shao-Liang
authors: SL
authors: Chen
mesh_terms: D000818:Animals; D062186:Arterial Pressure; D001343:Autophagy / Q000187:drug effects*; D001599:Berberine / Q000008:administration & dosage / Q000627:therapeutic use*; D015153:Blotting, Western; D001835:Body Weight / Q000187:drug effects; D006332:Cardiomegaly / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D002316:Cardiotonic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004452:Echocardiography; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects; D005355:Fibrosis; D008297:Male; D046529:Microscopy, Electron, Transmission; D009206:Myocardium / Q000378:metabolism / Q000648:ultrastructure; D009929:Organ Size / Q000187:drug effects; D012313:RNA / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020257:Ventricular Remodeling / Q000187:drug effects
chemical_list: D002316:Cardiotonic Agents; D001599:Berberine; D012313:RNA
keywords: Autophagy; Berberine; Berberine chloride (PubChem CID: 12456); Endoplasmic reticulum stress; Hypertrophy; Transverse aortic constriction