Albiflorin attenuates post-myocardial infarction cardiac fibrosis through inhibiting the RAS-ERK/MAPK signaling pathway.

BACKGROUND

Myocardial infarction (MI) frequently leads to acute heart failure. Albiflorin has been shown to exhibit multiple beneficial effects, including anti-inflammatory, anti-apoptotic, and anti-fibrotic activities. However, its precise molecular mechanisms in MI remain incompletely understood. In this study, we explored whether albiflorin could attenuate cardiac dysfunction following MI.

METHODS

Left anterior descending (LAD) coronary artery was ligated in mice and primary cardiac fibroblasts (CFs) was stimulated TGF-β1 to establish MI model. Network pharmacology was employed to identify potential targets between albiflorin and MI. Echocardiography, hematoxylin-eosin staining, Masson's trichrome staining, Western blot, and EdU assays were used to study the impact of albiflorin on MI. Furthermore, HRAS and NRAS overexpression models were established to validate the pharmacological mechanism of albiflorin.

RESULTS

In vivo experiments demonstrated that albiflorin significantly improved cardiac function and reduced myocardial fibrosis. In vitro studies revealed that albiflorin inhibited the TGF-β1-stimulated CFs proliferation and upregulation of αSMA and collagen I/III levels through the RAS-ERK/MAPK pathway. Mechanistically, albiflorin promoted ubiquitin-mediated degradation of HRAS and NRAS. Moreover, HRAS and NRAS overexpression partially reversed the inhibitory effects of albiflorin on CFs proliferation and expression of αSMA and collagen I/III.

CONCLUSION

Albiflorin improved cardiac function through suppressing CFs proliferation and inhibiting myofibroblast differentiation by modulation of the RAS-ERK/MAPK pathway.