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

Jie Huang1, Yang Liu2, Jia-xin Chen1, Xin-ya Lu1, Wen-jia Zhu1, Le Qin1, Zi-xuan Xun1, Qiu-yi Zheng1, Er-min Li1, Ning Sun1,3,4, Chen Xu1, Hai-yan Chen2
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
Correspondence to: Ning Sun:, Chen Xu:, Hai-yan Chen:,
DOI: 10.1038/s41401-021-00639-y
Received: 4 August 2020
Accepted: 4 March 2021
Advance online: 30 March 2021


Harmine is a β-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.
Keywords: cardiac hypertrophy; harmine; NE; hESCs-derived cardiomyocytes; inflammatory; SHR

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