Ginkgolide-A Alleviates Adjuvant-induced Rheumatoid Arthritis in Rats by Targeting TLR4/Myd88/NF-Κb Signaling Pathway

The present study investigated the effect of Ginkgolide-A (GA) on adjuvant-induced rheumatoid arthritis in rats and explored the underlying mechanism. The results demonstrated that rheumatoid arthri-tis induction caused a significant (p < 0.05) decrease in the body weight of the rats. However, treatment with GA significantly (p < 0.05) prevented the rheumatoid arthritis mediated decrease in body weight. Arthritis score in rats increased significantly (p < 0.05) from day-9 of CFA injection compared to the control group. The CFA-induced increase in arthritis score in rats was effectively alleviated by GA treatment. Treatment of the rats with GA significantly (p < 0.05) reversed CFA-injection induced increase of hind paw volume. Induction of rheumatoid arthritis led to a significant (p < 0.05) elevation in the production of TNF-a, IL-1i3 and IL-6 cytokines in rats. However, treatment of the rats with GA effectively reversed rheumatoid arthritis induced increase in the production of TNF-a, IL-1i3 and IL-6 cytokines. The rheumatoid arthritis induced increase in the level of IL-17A and IL-17F in rat serum was significantly (p < 0.05) alleviated by GA-treatment. The expression of MMP-1 and MMP-3 proteins in rheumatoid arthritis rats showed a prominent decrease whereas expression of TIMP-1 protein increased on treatment with GA. In summary, the present study demonstrates that GA treatment reverses adjuvant arthritis induced damage in rats and improves the symptoms of patho-genesis. The GA-treatment targets production of interleukins, tumor necrosis factor and upregulates TIMP-1 expression in rheumatoid arthritis rat mode. Moreover, the expression of MMP-1 and MMP-3 proteins is downregulated by GA-treatment in rats through targeting the NF-kappa B signal pathway. Therefore, GA may be developed as an effective therapeutic agent for the treatment of rheumatoid arthritis.