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In Pharmacological research ; h5-index 58.0

Cardiac hypertrophy (CH) is an enormous risk factor d in the process of heart failure development, however, there is still lacking of effective treatment for CH. Mitochondrial protection is an effective way against CH. Rheum palmatum L. (rhubarb) is used to treat chronic heart diseases such as heart failure, especially to inhibit cardiac compensatory enlargement. This study was to explore the pharmacodynamic component of rhubarb and reveal its pharmacological effects and targets in the treatment of CH. Based on network pharmacology and machine learning approach, ingredients of rhubarb and targets of CH were extracted and surflex docking was conducted for obtaining the optimal ingredient-target combination(s) and emodin-SIRT3 was obtained for further functional analysis. Transverse aortic constriction or isoproterenol induced CH mice and phenylephrine injured cardiomyocytes were used to verify the mitochondria protection effect and CH improvement of emodin in vivo and in vitro by modulation of mitochondrial SIRT3 signaling. The results showed that emodin can block agonist-induced and pressure overload-mediated CH. Emodin prevented mitochondrial dysfunction and its underlying mechanism was attributed to the activation of SIRT3, but the effect was not obvious with the presence of SIRT3 inhibitors (3-TYP)/SIRT3 siRNA. Furthermore, PGC-1ɑ was involved in the process of emodin regulating SIRT3 signaling pathway as an upstream target. Our findings clarified the main material basis and mechanism of rhubarb in the treatment of CH. Emodin, as the major ingredient of rhubarb, has therapeutic potential for CH through mitochondrial protection due to the modulation of SIRT3 signaling.

Gao Jian, Zhang Kunlin, Wang Yi, Guo Rui, Liu Hao, Jia Caixia, Sun Xiaoli, Wu Chaoyong, Wang Wei, Du Jie, Chen Jianxin

2020-Mar-02

SIRT3, cardiac hypertrophy, emodin, mitochondrial dysfunction, rheum palmatum L.