SND-117, a sinomenine bivalent alleviates type II collagen-induced arthritis in mice

Rheumatoid arthritis (RA) is a chronic, systemic inflammatory disorder that affects about 1% of the population worldwide. RA is mainly manifested by persistent synovitis and progressive joint destruction. The aim of the present study was to examine the anti-arthritis effects of SND-117, a sinomenine bivalent that is obtained from the structure modification of a clinically available anti-RA drug, sinomenine. The arthritis model (CIA) was established by immunizing DBA/1 mice with type II collagen, and the arthritis scores including inflammation, joint destruction and bone erosion were assessed after booster immunization for 3 weeks. The levels of cytokines such as IL-1 beta, IL-6 and TNF-alpha were analyzed by quantitative PR and ELISA. The TNF-alpha induced NF-kappa B activation in fibroblast-like synovial cells (FLSCs) was analyzed by Western blot. SND-117 significantly relieved the inflammatory symptoms of collagen-induced arthritis, reduced bone erosion and joint destruction in CIA mice. The serum levels of IL-1 beta, IL-6 and TNF-alpha of CIA mice were markedly decreased by SND-117. SND-117 also strongly inhibited the phosphorylation and nuclear translocation of NF-kappa B p65 in FLSCs upon TNF-alpha stimulation. These data demonstrated that SND-117 could effectively block the pathogenesis of collagen-induced arthritis in CIA mice via inhibition of NF-kappa B signaling, and might provide potential clinic benefits in rheumatoid arthritis management. (C) 2015 Elsevier B.V. All rights reserved.