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-alpha and IFN-gamma expression levels. SIN can significantly inhibit proliferation response of splenocytes induced by MBP(68-82). TNF-alpha and IFN-gamma, secreted by splenocytes induced by MBP(68-82) are inhibited by SIN by dose-dependence manner. The mRNA levels of CC chemokines, RANTES, MIP-1alpha 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.
Zeng
Yanying
Y
Department of Immunology, Nanjing Medical University, 140 Hanzhong Road, Nanjing 210029, China.
Gu
Bingjie
B
Ji
Xiaohui
X
Ding
Xinsheng
X
Song
Chunjie
C
Wu
Feichi
F
D000208:Acute Disease; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D020346:Aquaporins / Q000096:biosynthesis; D049109:Cell Proliferation / Q000187:drug effects; D018946:Chemokine CCL5 / Q000378:metabolism; D018925:Chemokines / Q000096:biosynthesis; D016207:Cytokines / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy* / Q000473:pathology; D005136:Eye Proteins / Q000096:biosynthesis; D005260:Female; D007371:Interferon-gamma / Q000096:biosynthesis / Q000235:genetics; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D009019:Morphinans / Q000494:pharmacology*; D051381:Rats; D011917:Rats, Inbred Lew; D054390:Receptors, CCR2; D019707:Receptors, Chemokine / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics
D000894:Anti-Inflammatory Agents, Non-Steroidal; D020346:Aquaporins; C515336:Ccr2 protein, rat; D018946:Chemokine CCL5; D018925:Chemokines; D016207:Cytokines; D005136:Eye Proteins; D008562:Membrane Glycoproteins; D009019:Morphinans; D054390:Receptors, CCR2; D019707:Receptors, Chemokine; D014409:Tumor Necrosis Factor-alpha; C030328:aquaporin 0; C009271:sinomenine; D007371:Interferon-gamma