Mechanistic Investigation of Wenfei Huaxian Decoction in the Treatment of Pulmonary Fibrosis Based on UPLC/Q-TOF-MS/MS, NetworkPharmacology, Experimental Validation, and Molecular Docking

INTRODUCTION: Idiopathic pulmonary fibrosis (IPF) is increasing and poses a major health threat. Although current treatments slow progression, their efficacy remains limited. Wenfei Huaxian Decoction (WFHX), a traditional Chinese medicinal formula, shows potential against IPF, though its mechanism remains unclear. To systematically elucidate the multicomponent and multi-target mechanisms underlying the anti- pulmonary fibrosis effects of WFHX by integrating ultra-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (UPLC/Q-TOF-MS/MS), network pharmacology, animal experiments, and molecular docking approaches. METHODS: WFHX components were analyzed using UPLC/Q-TOF-MS/MS, and potential targets were screened using online databases. Network pharmacology and enrichment analysis identified key components and pathways. A bleomycin-induced mouse model of pulmonary fibrosis validated these findings through cytokine profiling, histology, immunohistochemistry, and western blotting. Molecular docking assessed binding affinities between key components and their corresponding targets. RESULTS: UPLC/Q-TOF-MS/MS identified 48 WFHX compounds. Network pharmacology screening identified 935 overlapping targets among the compounds and disease-related genes. Quercetin and apigenin were identified as core active components, while NAMPT and SIRT1 were key molecular targets. Enrichment analysis linked WFHX to biological processes, including the inflammatory response, cell proliferation, epithelial-mesenchymal transition (EMT), and multiple signaling pathways. WFHX significantly alleviated pulmonary tissue damage, reduced inflammatory responses, and inhibited the progression of pulmonary fibrosis. CONCLUSION: This study elucidated the multidimensional anti-fibrotic mechanisms of WFHX using integrated techniques, supporting its clinical potential and modernization.