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

• SND-117 reduced arthritis, bone erosion and joint destruction in CIA mice.
• SND-117 inhibited the serum levels of IL-1β, IL-6 and TNF-α in vivo.
• SND-117 suppressed phosphorylation and nuclear translocation of NF-κB in fibroblast like synovial cells.
• SND-117 may possess potential clinic benefits in rheumatoid arthritis management.

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-1β, IL-6 and TNF-α were analyzed by quantitative PCR and ELISA. The TNF-α induced NF-κB 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-1β, IL-6 and TNF-α of CIA mice were markedly decreased by SND-117. SND-117 also strongly inhibited the phosphorylation and nuclear translocation of NF-κB p65 in FLSCs upon TNF-α stimulation. These data demonstrated that SND-117 could effectively block the pathogenesis of collagen-induced arthritis in CIA mice via inhibition of NF-κB signaling, and might provide potential clinic benefits in rheumatoid arthritis management.

Figure optionsDownload as PowerPoint slide