Investigating the therapeutic potential of jiawei xuanbi decoction in rheumatoid arthritis via network pharmacology and cell experiments

Rheumatoid arthritis (RA) is an autoimmune disease marked by symmetrical chronic polyarticular inflammation, which may increase the risk of disability in severe cases. Jiawei Xuanbi Decoction (JWXB), a traditional Chinese medicine formula, is commonly used for treating RA, but its specific molecular targets and action mechanisms in treating the disease remain unclear. RAW264.7 cells were induced to differentiate into osteoclasts by receptor activator of nuclear factor κ-B ligand (RANKL), and cell viability was evaluated via the MTT assay. Components of JWXB and RA-related targets were collected from Chinese Pharmacopoeia, SwissTargetPrediction, SuperPred, and GeneCard. Afterward, a protein-protein interaction (PPI) network was constructed using Cytoscape software. The key common targets were analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses via the DAVID6.8 database. AutoDock Vina software and iMODS platform were employed to perform molecular docking and molecular dynamics (MD) simulation to analyze the binding affinity between JWXB active components and targets. JWXB inhibited RANKL-induced osteoclast differentiation in vitro . A total of 164 targets associated with JWXB and RA were obtained, with AKT1 and STAT3 as key hubs in the PPI network. GO enrichment analysis revealed that these common targets were involved in biological processes like inflammatory response, protein phosphorylation, and regulation of cell proliferation. KEGG pathway analysis demonstrated that they were enriched in pathways including PI3K-Akt, TNF, NF-κB, and osteoclast differentiation pathways. Molecular docking and MD simulation results further confirmed stable binding between active components of JWXB (such as Tetrandrine and Demethyl tetrandrine) and key target genes (AKT1, SRC, and EGFR), with binding energies of all below −5 kcal/mol, indicating strong interactions. JWXB exerts anti-RA effects through multi-target/multi-pathway modulation of inflammation, osteoclast differentiation, and cell proliferation. These findings provide a scientific basis for JWXB’s clinical application and mechanism exploration.