Sinomenine inhibits the inflammatory responses of human fibroblast-like synoviocytes via the TLR4/MyD88/NF-κB signaling pathway in rheumatoid arthritis.

Abstract

Rheumatoid arthritis (RA) is a systemic autoimmune disorder mainly characterized by inflammation of the synovial tissue that can lead to destruction of bone and cartilage. Sinomenine is an alkaloid extracted from the stem of the Chinese medicinal plant Sinomenium acutum. It has been reported that sinomenine has immunosuppressive and anti-inflammatory properties. However, the molecular mechanism underlying the effect of sinominine on IL-1β-induced human RA fibroblast-like synoviocytes (RAFLS) is poorly understood. Therefore, in this study, we investigated the effect of sinomenine on the expression of inflammatory cytokines in IL-1β-treated human RAFLS in vitro and the underlying mechanism. RAFLS viability was evaluated using the MTS assay after sinomenine treatment. The levels of inflammatory cytokines were measured with ELISA, RT-PCR and western blot, respectively. The levels of TLR4 and its downstream signaling targets were determined by western blot analysis. We found that sinomenine suppressed not only NO and PGE2 production but also iNOS and COX-2 expression in IL-1β-induced RAFLS. It also inhibited the expression of TNF-α and IL-6 in IL-1β-stimulated RAFLS. Furthermore, sinomenine prevented IL-1β-induced TLR4, MyD88 and p-NF-κB p65 expression. Taken together, these results demonstrated that sinomenine prevented IL-1β-induced inflammation in human RAFLS at least in part by inhibiting the TLR4/MyD88/NF-κB signaling pathway, suggesting that sinomenine could be a potential agent in the treatment of RA.