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

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.