Ameliorating Effects of Murraya paniculata (L.) Jack Extract on Arthritis via Suppressing Multi‐Target‐Mediated Synovial Hyperplasia, Inflammation, and Oxidative Stress

Introduction Rheumatoid arthritis (RA) is a chronic autoimmune disorder characterized by persistent inflammation, synovial hyperplasia, and osteochondral damage. Murraya paniculata (L.) Jack (MP), a botanical source of Murrayae Folium et Cacumen (MFC), has not previously been investigated for its potential arthritis‐protective effects and underlying mechanisms, prompting our study of MP in this context. Objectives This study is aimed at evaluating the ameliorating effects of MP and elucidating its underlying mechanisms in RA. Methods The chemical composition of MP extract was analyzed using ultra‐performance liquid chromatography (UPLC). The anti‐arthritic effects of MP extract were assessed in collagen‐induced arthritis (CIA) rats and interleukin (IL)‐1β‐stimulated SW982 cells. Results UPLC quantification identified four major constituents: luteolin tetramethylether (0.547 ± 0.012%), 5,7,3′,4′,5′‐pentamethoxyflavone (1.558 ± 0.030%), 3′,4′,5,5′,6,7‐hexamethoxyflavone (0.273 ± 0.006%), and 5‐demethylnobiletin (0.848 ± 0.023%). In vivo, MP alleviated arthritis in CIA rats by reducing clinical symptoms (including arthritis index, hind paw volume/swelling, and histopathological joint damage), suppressing inflammatory responses, and attenuating oxidative stress. In vitro, MP mitigated pathological changes in IL‐1β‐stimulated SW982 cells by inhibiting cell proliferation and migration, dampening inflammation, and reducing oxidative stress. Furthermore, network pharmacology and transcriptomic analyses guided the investigation of MP's regulatory effects on key RA‐related targets. Specifically, MP downregulated IL‐1β‐induced overexpression of iNOS, COX‐2, and MMP2/9 in SW982 cells and inhibited AP‐1/NF‐κB activation. These effects were confirmed in vivo, where MP suppressed MMP2/9 expression and blocked AP‐1/NF‐κB activation in CIA rats. Conclusions Integrating phytochemical profiling, in vivo and in vitro models, network pharmacology‐transcriptomics, and target validation, this study demonstrates that MP exerts anti‐arthritic effects via modulating proliferation–inflammation–oxidation crosstalk.