Abstract

BACKGROUND Hepatic fibrosis represents a major global health burden with no approved first-line therapeutic agents. The urgent need for innovative targeted small molecule interventions has prompted investigation of natural compounds with anti-fibrotic potential. While α-amyrin demonstrates established anti-inflammatory properties, its therapeutic efficacy against hepatic fibrosis remains unexplored. PURPOSE The present study was designed to assess the anti-fibrotic efficacy of α-amyrin and determine its molecular mechanisms of action. STUDY DESIGN Firstly, the efficacy of α-Amyrin was evaluated through the liver fibrosis model. Further, the mechanism of α-Amyrin was analyzed using multi-omics and molecular biology experiments, and was verified using the target knockdown model. Finally, the effective components of α-Amyrin were analyzed through bioinformatics analysis and experimental verification. METHODS In this study, we use an in vitro model of fibrosis in human hepatic stellate LX-2 cells induced with TGF-β1 and an in vivo mouse model with CCl4 to evaluate the anti-fibrosis potential of α-Amyrin using multiple approaches. Employing multi-omics and molecular biology techniques to investigate the mechanism of α-Amyrin counteracting hepatic fibrosis. The interaction targets of α-Amyrin were examined through molecular docking, molecular dynamics simulations, and surface plasmon resonance. The anti-hepatic fibrosis mechanism of α-Amyrin was further validated using both in vitro and in vivo PPARα knockout or inhibition models. RESULTS