Swertiamarin ameliorates inflammation and osteoclastogenesis intermediates in IL-1β induced rat fibroblast-like synoviocytes

Objective and design Rheumatoid arthritis is a chronic inflammatory and autoimmune disease that leads to aggressive joint cartilage and bone destruction. Swertiamarin is a secoiridoid glycoside found in Enicostema axillare (Lam) A. Raynal, a medicinal plant used in the Indian system of traditional medicine. In the present study, the potential of swertiamarin was evaluated in IL-1 beta induced fibroblast-like synoviocytes (FLS). Methods The FLS were isolated from Freund's Complete Adjuvant induced arthritic (AA) rats and cultured with IL-1 beta. The normal FLS and AA-FLS were cultured and used for subsequent experiment in fibroblastic morphology form. The efficacy of swertiamarin (10-50 mu g/ml) was evaluated on mRNA and protein expression levels of inflammatory and osteoclastogenesis mediators. The efficacy was also evaluated on p38 MAPK alpha levels with time course studies (2, 4, 6, 8 and 12 h). Results IL-1 beta induced cell proliferation (149.46 +/- 13.73 %) and NO production (162.03 +/- 11.03 %) in AA-FLS; treatment with swertiamarin controlled proliferation (82.77 +/- 4.22 %) and NO production (82.06 +/- 3.91 % at 50 mu g/ml) in a dose-dependent manner. It also significantly (P < 0.05) modulated the expression of apoptotic marker (caspase 3), proinflammation mediators (TNF alpha, IL-6, PGE2, COX-2, iNOS, MMPs) and osteoclastogenic mediator (RANKL) at both the mRNA and protein levels. Treatment with swertiamarin inhibited the levels of p38 MAPK alpha in a dose-dependent manner and also significantly (P < 0.05) attenuated the release of the same in time dependent mode. Conclusion These findings suggest that treatment with swertiamarin attenuated IL-1 beta induced FLS, and it revealed anti-inflammatory potential by attenuating aggressive FLS.