| Objective To determine the molecular mechanism of ginkgetin in the treatment of rheumatoid arthritis. Methods The fibroblast-like synoviocytes (MH7A) were stimulated by TNF-α to establish inflammatory cell model, which were then treated with ginkgetin alone or together with si-TRAF3 or p38 agonist anisomycin. And we measured cell proliferation, apoptosis, the secretion of inflammatory cytokines interleukin-6 (IL-6) and IL-1β, and the expression of TRAF3 protein and phosphorylated p38 protein in MH7A cells. Furthermore, CIA rat model was constructed and ginkgetin was administered orally in rats. We evaluated arthritis index, paw swelling, synovial histopathology, and the expression of TRAF3 proteinand the levels of TNF-α, IL-6 and IL-1β in synovial tissues. Results Ginkgetin upregulated the expression of TRAF3, inhibited proliferation and inflammatory cytokine secretion, promoted apoptosis and blocked the p38 MAPK signaling pathway in MH7A cells. However, treatment with si-TRAF3 or anisomycin reversed the regulatory effects of ginkgetin on proliferation, apoptosis, inflammatory cytokine secretion and the p38 MAPK signaling pathway in MH7A cells. Moreover, ginkgolin treatment decreased arthritis index, paw swelling, and TNF-α, IL-6 and IL-1β secretion in CIA rats. Conclusion Ginkgetin upregulated TRAF3 expression, blocked p38 MAPK signaling pathway, inhibited MH7A cell proliferation and inflammatory cytokine secretion, promoted cell apoptosis, and further alleviated RA in CIA rats. |