Sinomenine, an Antirheumatic Alkaloid, Ameliorates Clinical Signs of Disease in the Lewis Rat Model of Acute Experimental Autoimmune Encephalolmyelitis

The therapeutic value of an antirheumatic alkaloid, sinomenine (SIN), was investigated in the acute experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis (MS). SIN is a bioactive alkaloid derived from the Chinese medicinal plant, Sinomenium acutum REHDER & E. H. WILSON (Family Menispermaceae). Chinese doctors have utilized this plant to treat rheumatic and arthritic diseases for over one thousand years. Experiments in which EAE-induced Lewis rats exhibit an acute monophasic episode of disease demonstrated that SIN is effective in preventing clinical signs of disease. The therapeutic effect on disease activity was observed at preonset administration times and at various doses tested. Consistent with disease activity in vivo, SIN-treated animals have reduced cellular infiltration within the spinal cord along with decreased TNF-α and IFN-γ expression levels. SIN can significantly inhibit proliferation response of splenocytes induced by MBP68—82. TNF-α and IFN-γ, secreted by splenocytes induced by MBP68—82 are inhibited by SIN by dose-dependence manner. The mRNA levels of CC chemokines, RANTES, MIP-1α and MCP-1, are inhibited in SIN-treated EAE rats. The data in this proof of concept study support the premise that SIN may be a promising new therapeutic intervention in MS.