Effect of sinomenine on collagen-induced arthritis in mice.
The present study was designed to investigate the effect of sinomenine (SIN), an alkaloid extracted from sinomenium acutum on collagen-induced arthritis (CIA) in mice. For this investigation, mice were s.c. immunized with type II collagen (CII) emulsified with complete Freund's adjuvant (day 0). Varying doses of SIN were orally administered daily commencing on day 0 daily over a period of 55 days. The severity of arthritis was evaluated according to clinical score, the effect of SIN on immune responses were determined by measurement of proliferative responses of spleen cells, antibody levels in serum and cytokine assays. Anti-CII IgG2a and IFN-gamma were measured as indicators of Th1 immune responses and anti-CII IgG1, IgE and IL-5 as those of Th2 responses. IL-10 and TGF-beta were measured as indicators of T cell regulator responses. The results showed that treatment with SIN was followed by decreases in the incidence and severity of CIA, anti-CII IgG and the antigen-specific splenocyte proliferation. Production of all isotypes of antibodies including anti-CII IgG2a, IgG1 and IgE as well as secretion of cytokines such as IFN-gamma and IL-5 were suppressed by SIN. In addition, SIN enhanced the secretion of TGF-beta while it had no obvious effect on production of IL-10. These results suggest that the anti-arthritic effect of SIN may be related to the suppression of both Th1 and Th2 immune responses. TGF-beta may at least in part contribute to the suppression of Th1 as well as Th2 immune responses.
Feng
H
H
Department of Pharmacology, Kobe Pharmaceutical University, Kobe, Hyogo, Japan.
Yamaki
K
K
Takano
H
H
Inoue
K
K
Yanagisawa
R
R
Yoshino
S
S
D000284:Administration, Oral; D000470:Alkaloids / Q000008:administration & dosage; D000818:Animals; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D001323:Autoantibodies / Q000276:immunology*; D049109:Cell Proliferation / Q000187:drug effects; D024043:Collagen Type II / Q000633:toxicity; D016207:Cytokines / Q000276:immunology; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D005620:Freund's Adjuvant / Q000633:toxicity; D051379:Mice; D009019:Morphinans / Q000008:administration & dosage*; D013154:Spleen / Q000276:immunology / Q000473:pathology; D018417:Th1 Cells / Q000276:immunology* / Q000473:pathology; D018418:Th2 Cells / Q000276:immunology* / Q000473:pathology
D000470:Alkaloids; D001323:Autoantibodies; D024043:Collagen Type II; D016207:Cytokines; D009019:Morphinans; C009271:sinomenine; D005620:Freund's Adjuvant