Skip to main content

Advertisement

Log in

Feeding Administration of Daikenchuto Suppresses Colitis Induced by Naive CD4+ T Cell Transfer into SCID Mice

  • Original Article
  • Published:
Digestive Diseases and Sciences Aims and scope Submit manuscript

Abstract

Background and Aims

Daikenchuto, a traditional Japanese herbal medicine, suppresses bacterial translocation by improvement of gastrointestinal motility and blood flow. As Daikenchuto reportedly reduces gastrointestinal inflammatory activity by these mechanisms, we analyzed whether Daikenchuto suppresses experimental colitis and reduces inflammatory cytokine expression in a mouse model.

Methods

Colitis was induced by transfer of naive CD4+ T cells of BALB/c mice into SCID mice, and mice were given either control or 2.7 % Daikenchuto-containing feed. We investigated body weight, clinical symptoms, histological changes, and Th1- and Th17-cytokine expression. Cytokine mRNA expression was analyzed using real-time RT-PCR. The ratio of IL-17+ and IFN-γ+ CD4+ T cells were analyzed by flow cytometry.

Results

Daikenchuto delayed the development of colitis and significantly reduced the histological inflammation scores. Analyses of cytokine mRNA revealed that Th17 cytokines were significantly decreased in colons of mice that received Daikenchuto. Absolute numbers of IL-17+ or IFN-γ+ CD4+ T cells per colon were less in mice receiving Daikenchuto than in mice that received control feed, as both groups received naive CD4+ T cells to induce colitis.

Conclusions

We demonstrated that feeding administration of Daikenchuto suppresses colitis induced by naive CD4+ T cell transfer into SCID mice. Daikenchuto may show clinical benefit in the treatment of human inflammatory bowel disease and further studies are warranted.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Fiocchi C. Inflammatory bowel disease: etiology and pathogenesis. Gastroenterology. 1998;115:182–205.

    Article  PubMed  CAS  Google Scholar 

  2. Lakatos P. Environmental factors affecting inflammatory bowel diseases: have we made progress? Dig Dis. 2009;27:215–225.

    Article  PubMed  Google Scholar 

  3. Xavier RJ, Podolsky DK. Unravelling the pathogenesis of inflammatory bowel disease. Nature. 2007;448:427–434.

    Article  PubMed  CAS  Google Scholar 

  4. Ardizzone S, Cassinotti A, Manes G, et al. Immunomodulators for all patients with inflammatory bowel disease? Therap Adv Gastroenterol. 2010;3:31–42.

    Article  PubMed  CAS  Google Scholar 

  5. Ito T, Yamakawa J, Mai M, et al. The effect of the herbal medicine dai-kenchu-to on post-operative ileus. J Int Med Res. 2002;30:428–432.

    Article  Google Scholar 

  6. Tokita Y, Yuzurihara M, Sakaguchi M, et al. The pharmacological effects of Daikenchuto, a traditional herbal medicine, on delayed gastrointestinal transit in Rat postoperative ileus. J Pharmacol Sci. 2007;104:303–310.

    Article  PubMed  CAS  Google Scholar 

  7. Sato K, Kase Y, Yuzurihara M, et al. Effect of Dai-kenchu-to (Da-Jian-Zhong-Tang) on the delayed intestinal propulsion induced by chlorpromazine in mice. J Ethnopharmacol. 2003;86:37–44.

    Article  Google Scholar 

  8. Murata P, Kase Y, Ishige A, et al. The herbal medicine Dai-kenchu-to and one of its active components 6-shogaol increase intestinal blood flow in rats. Life Sci. 2002;70:2061–2070.

    Article  PubMed  CAS  Google Scholar 

  9. Takayama S, Seki T, Watanabe M, et al. The herbal medicine daikenchuto increases blood flow in the superior mesenteric artery. Tohoku J Exp Med. 2009;219:319–330.

    Article  PubMed  Google Scholar 

  10. Quigley EM. Microflora modulation of motility. J Neurogastroenterol Motil. 2011;17:140–147.

    Article  PubMed  Google Scholar 

  11. Yoshikawa K, Kurita N, Higashijima J, et al. Kampo medicine “Dai-Kenchu-To” prevents bacterial translocation in rats. Dig Dis Sci. 2008;53:1824–1831.

    Article  PubMed  Google Scholar 

  12. Kono T, Kaneko A, Hira Y, et al. Anti-colitis and -adhesion effects of daikenchuto via endogenous adrenomedullin enhancement in Crohn’s disease mouse model. J Crohns Colitis. 2010;4:161–170.

    Article  PubMed  Google Scholar 

  13. Ogino H, Nakamura K, Ihara E, et al. CD4(+)CD25(+) regulatory T cells suppress Th17-responses in an experimental colitis model. Dig Dis Sci. 2011;56:376–386.

    Article  PubMed  CAS  Google Scholar 

  14. Mudter J, Wirtz S, Galle PR, Neurath MF. A new model of chronic colitis in SCID mice induced by adoptive transfer of CD62L + CD4 + T cells: insights into the regulatory role of interleukin-6 on apoptosis. Pathobiology. 2002;70:170–176.

    Article  PubMed  CAS  Google Scholar 

  15. Fantini MC, Becker C, Tubbe I, et al. Transforming growth factor β induced FoxP3 + regulatory T cells suppress Th1 mediated experimental colitis. Gut. 2006;55:671–680.

    Article  PubMed  CAS  Google Scholar 

  16. Siegmund B, Rieder F, Aldrich S, et al. Adenosine kinase inhibitor GP515 improves experimental colitis in mice. J Pharmacol Exp Ther. 2001;296:99–105.

    PubMed  CAS  Google Scholar 

  17. Honda K, Nakamura K, Matsui N, et al. T helper 1-inducing property of IL-27/WSX-1 signaling is required for the induction of experimental colitis. Inflamm Bowel Dis. 2005;11:1044–1052.

    Article  PubMed  Google Scholar 

  18. Yu Y, Sitaraman S, Gewirtz AT. Intestinal epithelial cell regulation of mucosal inflammation. Immunol Res. 2004;29:5–68.

    Article  Google Scholar 

  19. Berg RD. Bacterial translocation from the gastrointestinal tract. J Med. 1992;23:217–244.

    PubMed  CAS  Google Scholar 

  20. Alexander JW, Boyce ST, Babcock GF, et al. The process of microbial translocation. Ann Surg. 1990;212:496–512.

    Article  PubMed  CAS  Google Scholar 

  21. MacFie J, Reddy BS, Gatt M, et al. Bacterial translocation studied in 927 patients over 13 years. Br J Surg. 2006;93:87–93.

    Article  PubMed  CAS  Google Scholar 

  22. Wang YB, Liu J, Yang ZX. Effects of intestinal mucosal blood flow and motility on intestinal mucosa. World J Gastroenterol. 2011;17:657–661.

    Article  PubMed  CAS  Google Scholar 

  23. Shultz M, Strauch UG, Linde HJ, et al. Preventive effects of Escherichia coli strain Nissle 1917 on acute and chronic intestinal inflammation in two different murine models of colitis. Clin Diagn Lab Immunol. 2004;11:372–378.

    Google Scholar 

  24. Mazmanian SK, Round JL, Kasper DL. A microbial symbiosis factor prevents intestinal inflammatory disease. Nature. 2008;453:620–625.

    Article  PubMed  CAS  Google Scholar 

  25. Sartor RB. Therapeutic manipulation of the enteric microflora in inflammatory bowel disease: antibiotics, probiotics, and prebiotics. Gastroenterology. 2004;126:1620–1633.

    Article  PubMed  Google Scholar 

  26. Kruis W, Fric P, Pokrotnieks J, et al. Maintaining remission of ulcerative colitis with the probiotic Escherichia coli Nissle 1917 is as effective as with standard mesalazine. Gut. 2004;53:1617–1623.

    Article  PubMed  CAS  Google Scholar 

  27. Infante-Duarte C, Horton HF, Byrne MC, et al. Microbial lipopeptides induce the production of IL-17 in Th cells. J Immunol. 2000;165:6107–6115.

    PubMed  CAS  Google Scholar 

  28. Komiyama Y, Nakae S, Matsuki T, et al. IL-17 plays an important role in the development of experimental autoimmune encephalomyelitis. J Immunol. 2006;177:566–573.

    PubMed  CAS  Google Scholar 

  29. Nakae S, Nambu A, Sudo K, et al. Suppression of immune induction of collagen-induced arthritis in IL-17-deficient mice. J Immunol. 2003;171:6173–6177.

    PubMed  CAS  Google Scholar 

  30. Yen D, Cheung J, Scheerens H, et al. IL-23 is essential for T cell-mediated colitis promotes inflammation via IL-17 and IL-6. J Clin Invest. 2006;116:1310–1316.

    Article  PubMed  CAS  Google Scholar 

  31. Elson CO, Conq Y, Weaver CT, et al. Monoclonal anti-interleukin 23 reverses active colitis in a T cell-mediated model in mice. Gastroenterology. 2007;132:2359–2370.

    Article  PubMed  CAS  Google Scholar 

  32. Kobayashi T, Okamoto S, Hisamatsu T, et al. IL-23 differentially the Th1/Th17 balance in ulcerative colitis and Crohn’s disease. Gut. 2008;57:1682–1689.

    Article  PubMed  CAS  Google Scholar 

  33. Hölttä V, Klemetti P, Sipponen T, et al. IL-23/IL-17 immunity as a hallmark of Crohn’s disease. Inflamm Bowel Dis. 2008;14:1175–1184.

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

We thank Mr. Yohei Tokita and Dr. Masahiro Yamamoto for technical assistance. This work was supported in part by grants from the Japanese Ministry of Education, Culture, Sports, Science and Technology.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Kazuhiko Nakamura.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Iwasa, T., Ogino, H., Nakamura, K. et al. Feeding Administration of Daikenchuto Suppresses Colitis Induced by Naive CD4+ T Cell Transfer into SCID Mice. Dig Dis Sci 57, 2571–2579 (2012). https://doi.org/10.1007/s10620-012-2218-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10620-012-2218-0

Keywords

Navigation