Deciphering the therapeutic mechanisms of Pluchea lanceolata in Rheumatoid arthritis (RA) using network pharmacology,...

Rheumatoid arthritis (RA) is a complex, multi-dimensional autoimmune disorder that requires multi-targeted strategies in treatment management. This study has employed an integrated network pharmacology and computational studies approach to evaluate the anti-arthritic potential of Pluchea lanceolata. Twenty-two phytochemicals were retrieved from the IMPPAT database and screened for druggability and toxicity, yielding 15 candidates with favorable predicted drug-likeness and toxicity profiles. The disease phytotarget intersection and protein-protein interaction network analysis, when combined with the Venn-based consensus approach, resulted in eight key hub genes-PTGS2, MMP3, ESR1, ESR2, BCL2A1, CYP19A1, PTPRC, and DHFR, that were prioritized as potential hub targets associated with RA. The gene ontology and pathway enrichment analysis revealed the significant involvement in inflammatory pathways, including IL-17, NF-kappa-B, and TNF signaling. According to the molecular docking analysis, the 15 phytochemicals showed favorable predicted docking scores against the selected targets. Among them, Cycloart-23-en-3,25-diol (- 6.8 to - 11 kcal/mol), Isorhamnetin (- 6.3 to - 9.4 kcal/mol), and Pleuchiol (- 6.2 to - 9.7 kcal/mol) showed more favorable predicted docking scores than diclofenac (- 5.2 to - 7.9 kcal/mol) under the applied docking conditions across a range of targets. From MD results, the structure stability of PTGS2-Cycloart-23-en-3,25-diol complex is indicated and supported by RMSD, radius of gyration, residue-level fluctuations and hydrogen-bond profile. Overall, these findings suggest the potential multi-target activity of P. lanceolata and provide computationally derived hypotheses regarding its possible anti-rheumatoid mechanisms.

The online version contains supplementary material available at https://doi.org/10.1007/s40203-026-00772-8.