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

Int Immunopharmacol. 2008 Dec 20;8(13-14):1808-12. doi: 10.1016/j.intimp.2008.08.019. Epub 2008 Sep 17.

Abstract

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 IBD 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-small ka, CyrillicB 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.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use*
  • Chronic Disease
  • Colitis / drug therapy*
  • Colitis / immunology
  • Colitis / pathology
  • Colon / pathology
  • Disease Models, Animal
  • Diterpenes / therapeutic use*
  • Epoxy Compounds / therapeutic use
  • Immunosuppressive Agents / therapeutic use*
  • Interferon-gamma / biosynthesis
  • Interferon-gamma / drug effects
  • Interleukin-10 / genetics
  • Interleukin-12 / biosynthesis
  • Interleukin-23 / biosynthesis
  • Interleukin-23 / drug effects
  • Interleukin-4 / biosynthesis
  • Interleukin-4 / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • NF-kappaB-Inducing Kinase
  • Phenanthrenes / therapeutic use*
  • Protein Serine-Threonine Kinases / drug effects
  • Protein Serine-Threonine Kinases / metabolism
  • Serum Amyloid A Protein / biosynthesis
  • Serum Amyloid A Protein / drug effects
  • Tumor Necrosis Factor-alpha / biosynthesis
  • Tumor Necrosis Factor-alpha / drug effects

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Diterpenes
  • Epoxy Compounds
  • Immunosuppressive Agents
  • Interleukin-23
  • Phenanthrenes
  • Serum Amyloid A Protein
  • Tumor Necrosis Factor-alpha
  • Interleukin-10
  • Interleukin-12
  • triptolide
  • Interleukin-4
  • Interferon-gamma
  • Protein Serine-Threonine Kinases