FM0807 decelerates experimental arthritis progression by inhibiting inflammatory responses and joint destruction via modulating NF-κB and MAPK pathways

Background: Rheumatoid arthritis (RA) is a chronic articular synovial inflammatory disease. The precise etiology underlying the pathogenesis of RA remains unknown. We aimed to investigate the inhibitory effect of curcumin analogue FM0807 on experimental rheumatoid arthritis and investigate its possible mechanisms of action. Method: Rats with Freund9s complete adjuvant (FCA)-induced arthritis (AIA) were administered aspirin (0.1 mmol·kg−1), curcumin (0.1 mmol·kg−1), FM0807 (0.1, 0.2 mmol·kg−1) and vehicle via gastric gavage, from days 7 to 21, once daily. The hind paw volume and arthritis index (AI) were measured, and radiographic and histological examinations were performed. Twenty-one days later, the animals were sacrificed and left ankle joints were removed to measure protein expression of the elements of the NF-κB and MAPK pathway by western blot analysis. The enzyme-linked immunosorbent assay (ELISA) was employed to measure synovial fluid levels of TNF-α, IL-6, IL-1β and IL-10. Results: Compared with AIA group, FM0807 reduced the AI and swelling of the injected hind paw in a dose-dependent manner, and inhibited increases of inflammatory cell infiltration, pannus formation and cartilage destruction. FM0807 also potently attenuated the increase in the expression of inflammatory factors TNF-α, IL-6 and IL-1β in synovial fluid, while IL-10 levels were also elevated. FM0807 significantly suppressed phosphorylation of ERK1/2, JNK1/2, p38MAPK, IKK, IκB and NF-κB p65 protein, (all  p ＜0.05), which displayed more potential effects compared with those of the aspirin and curcumin groups. Conclusion: FM0807 exerts its therapeutic effects on RA by inhibiting cartilage degeneration. FM0807 treatment might be an effective therapeutic approach for RA.