Therapeutic effects of triptolide on interleukin-10 gene-deficient mice with colitis

Background: Triptolide, the principal active ingredient in the extract of Chinese herb Tripterygium wilfordii Hook, has both anti-inflammatory and immunomodulatory activities. However, the potential therapeutic role of triptolide in 1131) was still unknown. Interleukin-10 deficient mice, a well characterized experimental model of inflammatory bowel disease, spontaneously developed a Th1 T cell-mediated colitis with many similarities to Crohn's disease. This study was designed to investigate the therapeutic effect of triptolide on the chronic colitis in IL-10(-/-) mice. Methods: Triptolide was intraperitoneally administrated every another day for 8 weeks to IL-10(-/-) mice. The gross and histological appearances of the colon, the level of inflammatory mediators and transcription factor activation in the colon were evaluated and compared with the control group. Results: The 8-week administration of triptolide resulted in a significant decrease in the severity of colitis, together with lower production of TNF-alpha IFN-gamma and IL-4 in colon. The level of serum amyloid A was decreased in triptolide-treated mice. Gene expressions of IL-12 and IL-23 in colon were also downregulated after treatment. Furthermore, administration of triptolide markedly reduced NF-kappa B activation in colon mucosa of IL-10(-/-) mice. Conclusions: The efficacy of tritpolide treatment for the reduction of intestinal inflammation in IL-10(-/-) mice is a result of both anti-inflammatory and immunosuppressive activity. Triptolide holds significant potential for clinical applications for CD treatment. (C) 2008 Elsevier B.V. All rights reserved.