Skip to main content

Advertisement

Log in

Pulverized konjac glucomannan ameliorates oxazolone-induced colitis in mice

  • Original Contribution
  • Published:
European Journal of Nutrition Aims and scope Submit manuscript

Abstract

Purpose

Pulverized konjac glucomannan (PKGM) is a natural biologically active compound extracted from konjac, a Japanese traditional food. In the present study, we investigated the role of PKGM in intestinal immunity in a mouse model of oxazolone (OXA)-induced colitis.

Methods

C57BL/6(B6) mice were fed PKGM or control food from 2 weeks before the induction of OXA colitis. Body weight change, colon length, and histological change in the colon were examined. The mononuclear cells were purified from colon and stimulated with PMA/ionomycin. The levels of TNF-α, interferon (IFN)-γ, interleukin (IL)-4, and IL-13 from the supernatant were measured by ELISA.

Results

Oral administration of PKGM prevented the body weight loss and shortening of colon length associated with OXA-induced colitis. Histological analysis revealed that the colonic inflammation was improved by the administration of PKGM. The levels of IL-4 and IL-13, the critical inflammatory cytokines in OXA colitis, derived from mononuclear cells from the lamina propria of the colon were significantly suppressed by PKGM administration. PKGM-fed mice showed a significantly lower IL-4/IFN-γ ratio in the colonic lamina propria compared with that in control-fed mice. Fluorescence-activated cell sorting analysis revealed that natural killer (NK) 1.1+ T cells in the liver were significantly decreased in PKGM-fed mice. Finally, the preventive role of PKGM in OXA-induced colitis was not observed in invariant natural killer T cell-deficient mice.

Conclusions

PKGM ameliorated OXA-induced colitis in mice. This effect is associated with a decreased population of NK1.1+ T cells and induction of Th1-polarized immune responses.

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
Fig. 5

Similar content being viewed by others

Abbreviations

AD:

Atopic dermatitis

iNKT:

Invariant natural killer T

KGM:

Konjac glucomannan

LPMCs:

Lamina propria mononuclear cells

OXA:

Oxazolone

PKGM:

Pulverized konjac glucomannan

UC:

Ulcerative colitis

References

  1. Abraham C, Cho JH (2009) Inflammatory bowel disease. N Engl J Med 361:2066–2078

    Article  CAS  Google Scholar 

  2. Baumgart DC, Carding SR (2007) Inflammatory bowel disease: cause and immunobiology. Lancet 369:1627–1640

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  4. Baumgart DC, Sandborn WJ (2007) Inflammatory bowel disease: clinical aspects and established and evolving therapies. Lancet 369:1641–1657

    Article  CAS  Google Scholar 

  5. Vuksan V, Jenkins DJ, Spadafora P, Sievenpiper JL, Owen R, Vidgen E, Brighenti F, Josse R, Leiter LA, Bruce-Thompson C (1999) Konjac-mannan (glucomannan) improves glycemia and other associated risk factors for coronary heart disease in type 2 diabetes. A randomized controlled metabolic trial. Diabetes Care 22:913–919

    Article  CAS  Google Scholar 

  6. Ebihara K, Shneeman BO (1989) Interaction of bile acids, phospholipids, cholesterol and triglyceride with dietary fibers in the small intestine of rats. J Nutr 119:1100–1106

    CAS  Google Scholar 

  7. Chen HL, Fan YH, Chen ME, Chan Y (2005) Unhydrolyzed and hydrolyzed konjac glucomannans modulated cecal and fecal microflora in Balb/c mice. Nutrition 21:1059–1064

    Article  CAS  Google Scholar 

  8. Mizutani T, Mitsuoka T (1983) Effect of Konjac mannan on 1,2-dimethylhydrazine-induced intestinal carcinogenesis in Fischer 344 rats. Cancer Lett 19:1–6

    Article  CAS  Google Scholar 

  9. Onishi N, Kawamoto S, Nishimura M, Nakano T, Aki T, Shigeta S, Shimizu H, Hashimoto K, Ono K (2005) A new immunomodulatory function of low-viscous konjac glucomannan with a small particle size: its oral intake suppresses spontaneously occurring dermatitis in NC/Nga mice. Int Arch Allergy Immunol 136:258–265

    Article  CAS  Google Scholar 

  10. Matsuda H, Watanabe N, Geba GP, Sperl J, Tsudzuki M, Hiroi J, Matsumoto M, Ushio H, Saito S, Askenase PW, Ra C (1997) Development of atopic dermatitis-like skin lesion with IgE hyperproduction in NC/Nga mice. Int Immunol 9:461–466

    Article  CAS  Google Scholar 

  11. Onishi N, Kawamoto S, Nishimura M, Nakano T, Aki T, Shigeta S, Shimizu H, Hashimoto K, Ono K (2004) The ability of konjac-glucomannan to suppress spontaneously occurring dermatitis in NC/Nga mice depends upon the particle size. BioFactors 21:163–166

    Article  CAS  Google Scholar 

  12. Onishi N, Kawamoto S, Ueda K, Yamanaka Y, Katayama A, Suzuki H, Aki T, Hashimoto K, Hide M, Ono K (2007) Dietary pulverized Konjac glucomannan prevents the development of allergic rhinitis-like symptoms and IgE response in mice. Biosci Biotechnol Biochem 71:2551–2556

    Article  CAS  Google Scholar 

  13. Holma R, Juvonen P, Asmawi MZ, Vapaatalo H, Korpela R (2002) Galacto-oligosaccharides stimulate the growth of bifidobacteria but fail to attenuate inflammation in experimental colitis in rats. Scand J Gastroenterol 37:1042–1047

    Article  CAS  Google Scholar 

  14. Hoentjen F, Welling GW, Harmsen HJ, Zhang X, Snart J, Tannock GW, Lien K, Churchill TA, Lupicki M, Dieleman LA (2005) Reduction of colitis by prebiotics in HLA-B27 transgenic rats is associated with microflora changes and immunomodulation. Inflamm Bowel Dis 11:977–985

    Article  Google Scholar 

  15. Boirivant M, Fuss IJ, Chu A, Strober W (1998) Oxazolone colitis: a murine model of T helper cell type 2 colitis treatable with antibodies to interleukin 4. J Exp Med 188:1929–1939

    Article  CAS  Google Scholar 

  16. Heller F, Fuss IJ, Nieuwenhuis EE, Blumberg RS, Strober W (2002) Oxazolone colitis, a Th2 colitis model resembling ulcerative colitis, is mediated by IL-13-producing NK-T cells. Immunity 17:629–638

    Article  CAS  Google Scholar 

  17. Kuperman DA, Huang X, Koth LL, Chang GH, Dolganov GM, Zhu Z, Elias JA, Sheppard D, Erle DJ (2002) Direct effects of interleukin-13 on epithelial cells cause airway hyperreactivity and mucus overproduction in asthma. Nat Med 8:885–889

    CAS  Google Scholar 

  18. Fuss IJ, Strober W (2008) The role of IL-13 and NK T cells in experimental and human ulcerative colitis. Mucosal Immunol 1(Suppl 1):S31–S33

    Article  CAS  Google Scholar 

  19. Fuss IJ, Heller F, Boirivant M, Leon F, Yoshida M, Fichtner-Feigi S, Yang Z, Exley M, Kitani A, Blumberg RS, Mannon P, Strober W (2004) Nonclassical CD1d-restricted NK T cells that produce IL-13 characterize and atypical Th2 response in ulcerative colitis. J Clin Invest 113:1490–1497

    Article  CAS  Google Scholar 

  20. Kawano T, Cui J, Koezuka Y, Toura I, Kaneko Y, Sato H, Kondo E, Harada M, Koseki H, Nakayama T, Tanaka Y, Taniguchi M (1998) Natural killer-like nonspecific tumor cell lysis mediated by specific ligand-activated Vα14 NKT cells. Proc Natl Acad Sci USA 95:5690–5693

    Article  CAS  Google Scholar 

  21. Mudter J, Amoussina L, Schenk M, Yu J, Brüstle A, Weigmann B, Atreya R, Wirtz S, Becker C, Hoffman A, Atreya I, Biesterfeld S, Galle PR, Lehr HA, Rose-John S, Mueller C, Lohoff M, Neurath MF (2008) The transcription factor IFN regulatory factor-4 controls experimental colitis in mice via T cell-derived IL-6. J Clin Invest 118:2415–2426

    CAS  Google Scholar 

  22. Okamoto S, Watanabe M, Yamazaki M, Yajima T, Hayashi T, Ishii H, Mukai M, Yamada T, Watanabe N, Jameson BA, Hibi T (1999) A synthetic mimetic CD4 is able to suppress disease in a rodent model of immune colitis. Eur J Immunol 29:355–366

    Article  CAS  Google Scholar 

  23. Numata Y, Tazuma S, Ueno Y, Nishioka T, Hyogo H, Chayama K (2005) Therapeutic effect of repeated natural killer T cell stimulation in mouse cholangitis complicated by colitis. Dig Dis Sci 50:1844–1851

    Article  CAS  Google Scholar 

  24. Doi K, Matsuura M, Kawara A, Baba S (1979) Treatment of diabetes with glucomannan (konjac mannan). Lancet 1:987–988

    Article  CAS  Google Scholar 

  25. Kimata H (2006) Improvement of atopic dermatitis and reduction of skin allergic responses by oral intake of konjac ceramide. Pediatr Dermatol 23:386–389

    Article  Google Scholar 

  26. Uchiyama T, Nakano Y, Ueda O, Mori H, Nakashima M, Noda A, Ishizaki C, Mizoguchi M (2008) Oral intake of glucosylceramide improves relatively higher level of transepidermal water loss in mice and healthy human subjects. J Health Sci 54:559–566

    Article  CAS  Google Scholar 

  27. Suzuki H, Oomizu S, Yanase Y, Onishi N, Uchida K, Mihara S, Ono K, Kameyoshi Y, Hide M (2010) Hydrolyzed Konjac glucomannan suppresses IgE production in mice B cells. Int Arch Allergy Immunol 152:122–130

    Article  CAS  Google Scholar 

  28. Spergel JM, Mizoguchi E, Oettgen H, Bhan AK, Geha RS (1999) Roles of TH1 and TH2 cytokines in a murine model of allergic dermatitis. J Clin Invest 103:1103–1111

    Article  CAS  Google Scholar 

  29. Vestergaard C, Yoneyama H, Murai M, Nakamura K, Tamaki K, Terashima Y, Imai T, Yoshie O, Irimura T, Mizutani H, Matsushima K (1999) Overproduction of Th2-specific chemokines in NC/Nga mice exhibiting atopic dermatitis-like lesions. J Clin Invest 104:1097–1105

    Article  CAS  Google Scholar 

  30. Heller F, Florian P, Bojarski C, Richter J, Christ M, Hillenbrand B, Mankertz J, Gitter AH, Bürgel N, Fromm M, Zeitz M, Fuss I, Strober W, Schulzke JD (2005) Interleukin-13 is the key effector Th2 cytokine in ulcerative colitis that affects epithelial tight junctions, apoptosis, and cell restitution. Gastroenterology 129:550–564

    Article  CAS  Google Scholar 

  31. Mannon PJ, Hornung RL, Yang Z, Yi C, Groden C, Friend J, Yao M, Strober W, Fuss IJ (2011) Suppression of inflammation in ulcerative colitis by interferon-β-1a is accompanied by inhibition of IL-13 production. Gut 60:449–455

    Article  CAS  Google Scholar 

  32. Wilson MS, Ramalingam TR, Rivollier A, Shenderov K, Mentink-Kane MM, Madala SK, Cheever AW, Artis D, Kelsall BL, Wynn TA (2011) Colitis and intestinal inflammation in IL10-/- mice results from IL-13Rα2-mediated attenuation of IL-13 activity. Gastroenterology 140:254–264

    Article  CAS  Google Scholar 

  33. Zeissig S, Kaser A, Dougan SK, Nieuwenhuis EE, Blumberg RS (2007) Roles of NKT cells in the digestive system. III. Role of NKT cells in intestinal immunity. Am J Physiol Gastrointest Liver Physiol 293:G1101–G1105

    Article  CAS  Google Scholar 

  34. Wingender G, Kronenberg M (2008) Role of NKT cells in the digestive system. IV. The role of canonical natural killer T cells in mucosal immunity and inflammation. Am J Physiol Gastrointest Liver Physiol 294:G1–G8

    Article  CAS  Google Scholar 

Download references

Acknowledgments

We thank the Shimizu Chemical Co. and Nishikawa Rubber Co. for the donation of the PA (PROPOL®) and PKGM, respectively. This work was carried out at the Analysis Center of Life Science, Natural Science Center for Basic Research and Development, Hiroshima University.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Yoshitaka Ueno.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Onitake, T., Ueno, Y., Tanaka, S. et al. Pulverized konjac glucomannan ameliorates oxazolone-induced colitis in mice. Eur J Nutr 54, 959–969 (2015). https://doi.org/10.1007/s00394-014-0772-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00394-014-0772-2

Keywords

Navigation