Formononetin improves heart failure with preserved ejection fraction in mice by activating the PPARα/PGC-1 pathway  

作　　者：Hang Xu Xiaoqian Zhang Liming Huang Fei Li Yiyuan Tian Chao Guo Yi Ding Jing Ma Chao Liu 

机构地区：[1]Department of Traditional Chinese Medicine,Xijing Hospital,Fourth Military Medical University,Xi’an 710032,China [2]Department of Neonatology,the Second Affiliated Hospital of Shaanxi University of Chinese Medicine,Xianyang 712000,China [3]Department of Pharmacy,986 Hospital of People’s Liberation Army Air Force,Xi’an 710032,China [4]Department of Cardiology,Xijing Hospital,Fourth Military Medical University,Xi’an 710032,China [5]Department of Pharmacy,Xijing Hospital,Fourth Military Medical University,Xi’an 710032,China

出　　处：《Traditional Medicine Research》2024年第4期12-19,共8页TMR传统医学研究

基　　金：supported by the National Natural Science Foundation of China(82274313);Key R&D Program of Shaanxi Province(2023GHZD43);the National Natural Science Foundation of China(81870284).

摘　　要：Background:Formononetin(FMN)has beneficial effects in cardiovascular diseases but its functions and mechanisms in heart failure with preserved ejection fraction(HFpEF)remain unclear.This study aimed at determining whether FMN ameliorated HFpEF-induced cardiac dysfunction and exploring its underlying mechanisms.Methods:The mouse model of HFpEF was established through uninephrectomy surgery and d-aldosterone infusion in C57BL/6 mice.Cardiac remodeling and potential mechanisms of FMN in HFpEF were assessed by histological analysis,immunofluorescence,echocardiography,real-time PCR and western blotting sequentially.Results:FMN prevented myocardial dysfunction,fibrosis and cardiomyocyte apoptosis.The mRNA levels of left ventricular hypertrophy markers were increased in HFpEF mice but they remained unchanged in FMN-treated mice.In addition,the expression levels of PPARαand PGC-1 were increased in HFpEF mice for FMN treatment.The PPARα-PGC-1 complex affected the expression of fatty acid content and encoded enzymes in glucose metabolism.Both the hypertrophy and metabolic impairment due to FMN in HFpEF mice were alleviated after the addition of PPARαantagonist GW6471.Conclusion:In conclusion,FMN could prevent the cardiac hypertrophy in HFpEF mice by activating the PPARα/PGC-1 pathway and regulating energy metabolism,which provides a new therapeutic strategy for HFpEF patients.

关 键 词：FORMONONETIN heart failure with preserved ejection fraction PPARΑ PPARα/PGC-1 pathway energy metabolism 

分 类 号：X70[环境科学与工程—环境工程]