4.6 Article

Nanoparticle curcumin ameliorates experimental colitis via modulation of gut microbiota and induction of regulatory T cells

Journal

PLOS ONE
Volume 12, Issue 10, Pages -

Publisher

PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0185999

Keywords

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Funding

  1. Ministry of Education, Culture, Sports, Science and Technology of Japan [15K08967, 15K19322]
  2. Ministry of Health, Labor and Welfare of Japan [067]
  3. Japan Agency for Medical Research and Development, AMED [15AeK0109047h0002]
  4. Smoking Research Foundation [1848]
  5. Intractable Diseases from the Ministry of Health, Labor and Welfare of Japan [067]
  6. Practical Research Project for Rare/Intractable Diseases from the Japan Agency for Medical Research and Development, AMED [15AeK0109047h0002]
  7. Grants-in-Aid for Scientific Research [15K08948, 16K09846, 15K19322] Funding Source: KAKEN

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Background and Aims Curcumin is a hydrophobic polyphenol derived from turmeric, a traditional Indian spice. Curcumin exhibits various biological functions, but its clinical application is limited due to its poor absorbability after oral administration. A newly developed nanoparticle curcumin shows improved absorbability in vivo. In this study, we examined the effects of nanoparticle curcumin (named Theracurmin) on experimental colitis in mice. Methods BALB/c mice were fed with 3% dextran sulfate sodium (DSS) in water. Mucosal cytokine expression and lymphocyte subpopulation were analyzed by real-time PCR and flow cytometry, respectively. The profile of the gut microbiota was analyzed by real-time PCR. Results Treatment with nanoparticle curcumin significantly attenuated body weight loss, disease activity index, histological colitis score and significantly improved mucosal permeability. Immunoblot analysis showed that NF-kappa B activation in colonic epithelial cells was significantly suppressed by treatment with nanoparticle curcumin. Mucosal mRNA expression of inflammatory mediators was significantly suppressed by treatment with nanoparticle curcumin. Treatment with nanoparticle curcumin increased the abundance of butyrate-producing bacteria and fecal butyrate level. This was accompanied by increased expansion of CD4(+) Foxp3(+) regulatory T cells and CD103(+) CD8 alpha(-) regulatory dendritic cells in the colonic mucosa. Conclusions Treatment with nanoparticle curcumin suppressed the development of DSS-induced colitis potentially via modulation of gut microbial structure. These responses were associated with induction of mucosal immune cells with regulatory properties. Nanoparticle curcumin is one of the promising candidates as a therapeutic option for the treatment of IBD.

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