Abstract
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.
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Acknowledgements
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.
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JH, NS, CX, and HYC designed the research and wrote the manuscript; JH, YL, JXC, XYL, WJZ, LQ, and ZXX performed the experiment; YL and HYC contributed equipment and analytic tools; JH, JXC, XYL, LQ, ZXX, QYZ, and EML analyzed the data.
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Huang, J., Liu, Y., Chen, Jx. et al. Harmine is an effective therapeutic small molecule for the treatment of cardiac hypertrophy. Acta Pharmacol Sin 43, 50–63 (2022). https://doi.org/10.1038/s41401-021-00639-y
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DOI: https://doi.org/10.1038/s41401-021-00639-y
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