Linggui Zhugan Decoction mitigates post-myocardial infarction heart failure through modulation of cardiomyocyte F-actin cytoskeletal organization.

Abstract

BACKGROUND: Linggui Zhugan Decoction (LGZGD), a traditional Chinese formula for spleen-strengthening and yang-warming to resolve fluid retention, has consistently shown efficacy in preventing and treating heart failure. However, its underlying biological mechanisms remain incompletely understood. OBJECTIVE: This study aimed to investigate the therapeutic efficacy of LGZGD in a rat model of heart failure and in H9C2 cardiomyocytes, as well as to elucidate its effects on F-actin remodeling and the underlying mechanisms. METHODS: A rat model of heart failure post-myocardial infarction was established by ligating the left anterior descending coronary artery, followed by treatment with LGZGD for 4 weeks. The chemical constituents of the decoction and drug-containing serum were characterized using ultra-performance liquid chromatography. Network pharmacology analysis identified potential key therapeutic targets of LGZGD for heart failure treatment. An in vitro hypoxia/reoxygenation injury model was constructed in H9C2 cardiomyocytes. Additionally, siRNA-mediated ROCK knockdown was performed to investigate the mechanisms underlying LGZGD-mediated regulation of F-actin remodeling in cardiomyocytes. RESULTS: The results showed that LGZGD significantly improved cardiac function and pathological morphology in heart failure rats. Network pharmacology analysis identified RhoA as a key potential target for LGZGD in regulating F-actin in heart failure. Both in vivo and in vitro experiments further confirmed that LGZGD modulates F-actin cytoskeletal remodeling. CONCLUSION: The present findings indicate that LGZGD significantly improves cardiac function in rats with heart failure. Furthermore, it enhances the stability of F-actin cytoskeletal organization and function in both heart tissues from rats with heart failure and H9C2 cardiomyocytes.