Sinomenine reduces iNOS expressionvia inhibiting the T-bet IFN-γ pathway in experimental autoimmune encephalomyelitis in rats

Sinomenine is a bioactive alkaloid isolated from the Chinese medicinal plant Sinomenium acutum.It is widely used as an immunosuppressive drug for treating rheumatic and arthritic diseases.In our previous studies,we found that sinomenine reduced cellular infiltration within the spinal cord and alleviated experimental autoimmune encephalomyelitis(EAE) in rats.In this study,we further investigated the mechanisms of sinomenine treatment in EAE rats.In EAE rats,treatment with sinomenine exerted an anti-inducible NO synthase(anti-iNOS) effect,which is related to the reductions of Th1 cytokine interferon-γ(IFN-γ) and its transcription factor,T-bet,in spinal cords.Moreover,sinomenine treatment of splenocytes stimulated with anti-CD3 antibody and recombinant rat interleukin 12 reduced the expression of T-bet and IFN-γ in vitro and also reduced the capability of supernatants of splenocyte culture to induce iNOS expression by primary astrocytes.However,sinomenine had no direct inhibitory effect on iNOS produced by astrocytes cultured with IFN-γ and tumor necrosis factor α in vitro.In conclusion,the anti-iNOS effect of sinomenine on EAE is mediated via the suppression of T-bet /IFN-γ pathway.