Mangiferin exert protective effects on joints of adjuvant-induced arthritis rats by regulating the MAPKs/NF-κB pathway of fibroblast-like synoviocytes

Mangiferin (MF) is a bioactive ingredient predominantly isolated from the mango tree, that has been reported to have antioxidant, anti-inflammatory, and immunomodulatory effects. This study was aimed to investigate the protective effect of MF on the joints of arthritic rats and explore the underlying mechanisms of this function.Adjuvant-induced arthritis (AA) rat model was established and clinical severity of AA was evaluated by arthritis index, paw edema, plasma, and synovium homogenate parameters. The severity of joint destruction was assessed by radiological and histopathological. Immunohistochemical analysis was employed to detect the protein expression of MMP-3, MMP-13 in synovium and cartilage tissues. The vitro effects of MF on proliferation, migration, apoptosis, and production of inflammatory mediators in RA- FLSs were determined by the CCK8 assay, transwell assay, flow cytometry, and real-time PCR, respectively.The results demonstrated that MF treatment significantly alleviated arthritis index, paw swelling and decreased the secretion of inflammatory cytokines in plasma and synovium. Meanwhile, MF inhibited synovial inflammation, pannus formation, and bone erosion in AA rats. It also ameliorated the oxidative stress state of arthritic rats via modulating the level of MDA, SOD, CAT, GSH, NO. In addition, MF effectively attenuated the destructive behavior of RA-FLSs by inhibiting proliferation, migration, and secretion of inflammatory mediators, and promoting apoptosis. The further mechanistic analysis demonstrated that MF might exert an antiarthritic effect via inhibiting the pathway of MAPKs (ERK2 and p38) and NF-κ B.Taken together, our results demonstrated that MF would be a promising anti-arthritic agent candidate for further research.