Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive fibrotic disease with an unclear etiology and no effective treatment. This study aims to elucidate the pathogenic mechanism networks involving multiple targets and pathways in IPF. Extracts and metabolites of Astragali Radix (AR) and Angelicae Sinensis Radix (ASR), two well-known traditional Chinese medicines, have demonstrated therapeutic effects on IPF. However, the underlying mechanisms of AR and ASR remain unclear. Utilizing network pharmacology analysis, the disease targets associated with IPF were obtained from the GeneCards database and Online Mendelian Inheritance in Man (OMIM) database. Targets of AR and ASR were identified using the Traditional Chinese Medicine (TCM) Systems Pharmacology Database and Analysis Platform and Swiss Target Prediction. A proteinprotein interaction (PPI) network was subsequently constructed and analyzed using the STRING database and Cytoscape software. Gene ontology enrichment (GO) analysis and kyoto encyclopedia of genes and genomes (KEGG) analysis were conducted using DAVID. Additionally, a component-target-pathway network was employed to identify the main active components, and molecular docking was performed between these components and proteins encoded by key targets. Finally, in vitro studies were conducted based on network pharmacology. A total of 260 common targets between IPF and drug targets were identified and included in the PPI network, in which TNF, IL-6, STAT3, AKT1, VEGFA, SRC, EGFR, INS, JUN, and IL1B were predicted as key targets. These 260 targets were enriched in the PI3K-AKT signaling pathway, HIF-1 signaling pathway, TNF signaling pathway, MAPK signaling pathway, FOXO signaling pathway, and Pathways in cancer. Docking scores ranged from -4.1 to -9.5 kcal/mol, indicating a strong binding affinity between the main active compounds and key targets. In vitro studies have indeed shown that Quercetin and Magnolol can alleviate the expression of epithelial-mesenchymal transition in the A549 cells caused by IL-6. The treatment with AR and ASR resulted in a reduction of mRNA levels for key targets HIF-1 alpha and alpha-SAM. Additionally, the protein expression levels of P-JAK2/ JAK2, P-STAT3/ STAT3, and alpha-SMA/ beta-Actin were also reduced. These results support the therapeutic potential of AR and ASR in ameliorating pulmonary fibrosis and provide insight into the molecular mechanisms involved in their therapeutic effects.
