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 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.
Wei
Xiaowei
X
Department of General Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, PR China.
Gong
Jianfeng
J
Zhu
Juan
J
Niu
Lingying
L
Zhu
Weiming
W
Li
Ning
N
Li
Jieshou
J
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D002908:Chronic Disease; D003092:Colitis / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D003106:Colon / Q000473:pathology; D004195:Disease Models, Animal; D004224:Diterpenes / Q000627:therapeutic use*; D004852:Epoxy Compounds / Q000627:therapeutic use; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007371:Interferon-gamma / Q000096:biosynthesis / Q000187:drug effects; D016753:Interleukin-10 / Q000235:genetics; D018664:Interleukin-12 / Q000096:biosynthesis; D053759:Interleukin-23 / Q000096:biosynthesis / Q000187:drug effects; D015847:Interleukin-4 / Q000096:biosynthesis / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010616:Phenanthrenes / Q000627:therapeutic use*; D017346:Protein Serine-Threonine Kinases / Q000187:drug effects / Q000378:metabolism; D000685:Serum Amyloid A Protein / Q000096:biosynthesis / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000187:drug effects; D000097782:NF-kappaB-Inducing Kinase
D000894:Anti-Inflammatory Agents, Non-Steroidal; D004224:Diterpenes; D004852:Epoxy Compounds; D007166:Immunosuppressive Agents; D007371:Interferon-gamma; D016753:Interleukin-10; D018664:Interleukin-12; D053759:Interleukin-23; D015847:Interleukin-4; D010616:Phenanthrenes; D017346:Protein Serine-Threonine Kinases; D000685:Serum Amyloid A Protein; D014409:Tumor Necrosis Factor-alpha; D000097782:NF-kappaB-Inducing Kinase; C001899:triptolide