Berberine improves pressure overload-induced cardiac hypertrophy and dysfunction through enhanced autophagy

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• 作者：Ming-Hui Li^a ; ¹ ; Yao-Jun Zhang^a ; ¹ ; Yi-Hui Yu^a ; ¹ ; Shao-Hua Yang^a ; Javaid Iqbal^b ; Qiong-Yu Mi^c ; Bing Li^a ; Zhi-Mei Wang^a ; Wen-Xing Mao^a ; Hong-Guang Xie^c ; ^d ; Shao-Liang Chen^a ; ^{chmengx126@gmail.com" class="auth_mail}
• 关键词：Berberine chloride (PubChem CID ; 12456)
• 刊名：European Journal of Pharmacology
• 出版年：5 April, 2014
• 年：2014
• 卷：728
• 期：Complete
• 页码：67-76
• 全文大小：8105 K

文摘

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.