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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.