摘要Rheumatoid arthritis(RA)is a chronic,progressive autoimmune disorder characterized by persistent synovial inflammation,pannus formation,bone erosion,and eventual joint de-struction.Murraya exotica L.(ME),a botanical source of Murrayae Folium et Cacumen(MFC),has not been previously investigated for its anti-arthritic potential,which motivated this study.The chemical composition of ME was characterized using ultra-performance liquid chromatography(UPLC),and its anti-arthritic effects were evaluated in collagen-induced arthritis(CIA)rats and interleukin(IL)-1β-stimulated SW982 cells.The contents of meranzin hydrate,hainanmurpanin,murrayone,and 3',4',5,5',6,7-hexamethoxyflavone in the ME ex-tract were quantified as 2.86％±0.01％,1.88％±0.01％,0.07％±0.00％,and 0.01％±0.00％,respectively.In CIA rats,ME treatment alleviated clinical symptoms,attenuated histopatholo-gical joint damage,including synovial hyperplasia,cartilage degeneration,and bone erosion,ameliorated inflammation,and reduced oxidative stress.In IL-1β-stimulated SW982 cells,ME inhibited proliferation and migration,suppressed the inflammatory response,and mitigated oxidative stress.Network pharmacology and molecular docking analyses predicted strong in-teractions between ME-derived compounds(e.g.,murrayone)and nuclear factor-kappa B(NF-κB)p65,which were further validated by cellular thermal shift assay(CETSA)and drug affin-ity responsive target stability(DARTS)assay.Mechanistically,ME blocked NF-κB activation by inhibiting phosphorylation and degradation of inhibitor of NF-κB-α(IκBα)and preventing p65 nuclear translocation,while simultaneously suppressing activator protein-1(AP-1)activ-ation through downregulation of c-Fos and c-Jun.The involvement of the NF-κB and AP-1 pathways in ME-mediated anti-inflammatory,anti-proliferative,and anti-oxidative effects in RAwas further confirmed using specific pharmacological inhibitors:pyrrolidinedithiocar-bamate(PDTC)for NF-κB and SR11302 for AP-1.