Formononetin regulates dilated cardiomyopathy-mediated heart failure in rats via HSP90/AKT cardiomyocyte apoptosis and mechanism

Yuying QI; Songyan Xue; Weijia Chen; Ting Jia; Zhizheng Xing; Huan Liu; Jing MA

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Formononetin regulates dilated cardiomyopathy-mediated heart failure in rats via HSP90/AKT cardiomyocyte apoptosis and mechanism

VernacularTitle:芒柄花素通过HSP90/AKT调控扩张型心肌病心力衰竭大鼠心肌细胞凋亡及其机制
Author: Yuying QI ^{1
,

2} ; Songyan XUE ³ ; Weijia CHEN ³ ; Ting JIA ³ ; Zhizheng XING ³ ; Huan LIU ³ ; Jing MA ³
Author Information

1. College of Life Science, Northwest University, Xian 710069
2. Traditional Chinese Medicine Department, First Air Force Medical University Hospital, Xi’an 710032, China
3. Traditional Chinese Medicine Department, First Air Force Medical University Hospital, Xi’an 710032, China
Publication Type:Journal Article
Keywords: formononetin; dilated cardiomyopathy mediated heart failure; HSP90; AKT; cardiomyocyte apoptosis
From: Journal of Xi'an Jiaotong University(Medical Sciences) 2023;44(5):794-801
CountryChina
Language:Chinese
Abstract: 【Objective】 To investigate the effects of formononetin (FMN) on cardiomyocyte apoptosis and HSP90/AKT in rats with dilated cardiomyopathy-mediated heart failure. 【Methods】 Echocardiography, ELISA, histological staining, and TUNEL staining were used to observe the protective effect of different doses of FMN on dilated cardiomyopathy-mediated heart failure in rats and the apoptosis of cardiomyocytes. The potential targets of formononetin on dilated cardiomyopathy-mediated heart failure were obtained from TCMSP, DisGeNet, GeneCards, and other databases, the key targets were obtained according to the protein-protein interaction (PPI) network, and the key targets were verified by molecular docking. Western blotting was used to further verify the regulatory role of key targets in the treatment of dilated cardiomyopathy-mediated heart failure with formononetin. 【Results】 Formononetin could reduce the levels of LVIDS, LVIDD, NT-pro BNP, cTn-T, CK, CK-MB, and LDH in rats with dilated cardiomyopathy-mediated heart failure, increase the levels of EF and FS, and reduce the apoptosis of cardiomyocytes. FMN had a strong binding effect on 10 key targets (AKT1, HSP90AA1, CASP3, MAPK1, MMP9, SRC, ALB, HRAS, IGF1, and EGFR) screened by network pharmacology, with HSP90AA1 and AKT1 having the strongest binding effect. Formononetin decreased the expression of HSP90, AKT and downstream CASP3 protein, but increased the expression of p-AKT in myocardial tissue. 【Conclusion】 Formononetin may inhibit the expression of HSP90, promote phosphorylation of AKT to p-AKT, and inhibit the expression of CASP3, thereby reducing the apoptosis of cardiomyocytes and improving myocardial tissue damage, so as to achieve the purpose of treating dilated cardiomyopathy-mediated heart failure.