Harmine is an effective therapeutic small molecule for the treatment of cardiac hypertrophy  

作　　者：Jie Huang Yang Liu Jia-xin Chen Xin-ya Lu Wen-jia Zhu Le Qin Zi-xuan Xun Qiu-yi Zheng Er-min Li Ning Sun Chen Xu Hai-yan Chen 

机构地区：[1]Department of Physiology and Pathophysiology,State Key Laboratory of Medical Neurobiology,School of Basic Medical Sciences,Fudan University,Shanghai,200032,China [2]Department of Echocardiography,Zhongshan Hospital,Fudan University,Shanghai,200032,China [3]Shanghai Key Lab of Birth Defect,Children’s Hospital of Fudan University,Shanghai,201100,China [4]Research Center on Aging and Medicine,Fudan University,Shanghai,200032,China

出　　处：《Acta Pharmacologica Sinica》2022年第1期50-63,共14页中国药理学报（英文版）

基　　金：We thank Chemical Biology Core Facility of SIBCB for technical supports.We also thank Ming Chen,Shu-jue Lan,Shuai Han,Hong-wei Zhao,Yun-qing Ci,and Rong-chao Yang(SIBCB)for their experimental assistance.This work was supported by the National Natural Science Foundation of China#82070391(to NS),#81500241(to CX);by the Innovative Research Team of High-Level Local Universities in Shanghai;by the National Key R&D Program of China 2018YFC2000202,the Haiju program of National Children’s Medical Center EK1125180102.

摘　　要：Harmine is aβ-carboline alkaloid isolated from Banisteria caapi and Peganum harmala L with various pharmacological activities,including antioxidant,anti-inflammatory,antitumor,anti-depressant,and anti-leishmanial capabilities.Nevertheless,the pharmacological effect of harmine on cardiomyocytes and heart muscle has not been reported.Here we found a protective effect of harmine on cardiac hypertrophy in spontaneously hypertensive rats in vivo.Further,harmine could inhibit the phenotypes of norepinephrine-induced hypertrophy in human embryonic stem cell-derived cardiomyocytes in vitro.It reduced the enlarged cell surface area,reversed the increased calcium handling and contractility,and downregulated expression of hypertrophy-related genes in norepinephrine-induced hypertrophy of human cardiomyocytes derived from embryonic stem cells.We further showed that one of the potential underlying mechanism by which harmine alleviates cardiac hypertrophy relied on inhibition of NF-κB phosphorylation and the stimulated inflammatory cytokines in pathological ventricular remodeling.Our data suggest that harmine is a promising therapeutic agent for cardiac hypertrophy independent of blood pressure modulation and could be a promising addition of current medications for cardiac hypertrophy.

关 键 词：cardiac hypertrophy HARMINE NE hESCs-derived cardiomyocytes INFLAMMATORY SHR 

分 类 号：R54[医药卫生—心血管疾病] R96[医药卫生—内科学]