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
• 来源期刊: 中国药理学报（英文版）
• 年，卷（期）: 2022,（1）
• 所属期刊栏目: Cardlovascular Pharmacology
• 页码范围: 50-63
• 页数: 14页
• 语种: 英文

摘要

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-KB 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.