Synovial hyperplasia, inflammatory responses, and oxidative stress play a crucial role in the progression of rheumatoid arthritis, however, current mainstream therapies primarily focus on broad immunosuppression with limited efficacy and suboptimal safety profiles, and the precise molecular mechanisms by which Murraya exotica L. extract improves arthritis remain insufficiently explored.Here, we elucidate the anti-arthritic effects of Murraya exotica L. extract in a collagen-induced arthritis rat model and in IL-1β-stimulated SW982 synoviocytes, and demonstrate that it inhibits fibroblast-like synoviocyte proliferation and migration, reduces inflammatory cytokine release, and mitigates oxidative stress by blocking NF-κB activation (preventing IκBα degradation and p65 nuclear translocation) and suppressing AP-1 activation (downregulating c-Fos and c-Jun). Integrated with network pharmacology, molecular docking, and cellular thermal shift assay (CETSA) and DARTS assays, we further identify NF-κB p65 as a direct target and murrayone as a primary active constituent responsible for these effects, which was further validated using specific pharmacological inhibitors PDTC and SR11302.
This work provides a comprehensive theoretical foundation elucidating the critical role of the NF-κB/AP-1 axis in rheumatoid arthritis progression and clarifies the active substance basis and direct targets of Murraya exotica L. extract. The work entitled “Potential therapeutic benefits of Murraya exotica L. extract on type II collagen-induced arthritis” was published on Chinese Journal of Natural Medicines (published on May 20, 2026).

DOI: 10.1016/S1875-5364(26)61179-X