Integrative analysis of the therapeutic mechanisms of Astragaloside IV in idiopathic pulmonary fibrosis via network pharmacology and molecular validation.

Astragaloside IV (AS-IV), an essential active ingredient isolated from Astragalus membranaceus, has exhibited notable antifibrotic properties in diverse disease models. However, its exact role and underlying molecular mechanisms in idiopathic pulmonary fibrosis (IPF) remain insufficiently defined. In this study, we employed an integrative approach combining transcriptomic profiling, network pharmacology, and molecular docking techniques to investigate the critical targets and signaling pathways modulated by AS-IV in the context of IPF. Differentially expressed genes obtained from lung tissue datasets of IPF patients were cross-referenced with AS-IV-associated targets to identify overlapping candidates with potential therapeutic relevance. Gene enrichment analyses revealed that the PI3K-AKT pathway plays a central role in mediating AS-IV's biological effects. Molecular docking and subsequent dynamic simulations demonstrated that AS-IV binds stably to the PIK3CA protein. In vitro experiments confirmed that AS-IV suppressed the activation of fibroblasts and decreased the expression of fibrotic markers. Furthermore, in a bleomycin-induced mouse model, AS-IV administration significantly reduced collagen accumulation and pulmonary fibrosis. These results collectively suggest that AS-IV exerts protective effects against IPF progression primarily through modulation of the PI3K-AKT pathway by targeting PIK3CA, supporting its potential development as a novel antifibrotic therapeutic agent.