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

PLoS One. 2017 Oct 6;12(10):e0185999. doi: 10.1371/journal.pone.0185999. eCollection 2017.

Abstract

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-κB 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+ CD8α- 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.

MeSH terms

  • Animals
  • Colitis / chemically induced
  • Colitis / drug therapy*
  • Colitis / metabolism
  • Colitis / microbiology
  • Curcumin / administration & dosage
  • Curcumin / therapeutic use*
  • Cytokines / metabolism
  • Dextran Sulfate
  • Disease Models, Animal
  • Gastrointestinal Microbiome / drug effects*
  • Intestinal Mucosa / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Nanoparticles / administration & dosage
  • Nanoparticles / therapeutic use*
  • T-Lymphocytes, Regulatory / drug effects*
  • T-Lymphocytes, Regulatory / immunology

Substances

  • Cytokines
  • Dextran Sulfate
  • Curcumin

Grants and funding

This work was supported by a Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan; https://www.jsps.go.jp/english/e-grants/index.html, 15K08967 to A.A and 15K19322 to A.N., the Intractable Diseases from the Ministry of Health, Labor and Welfare of Japan http://www.nanbyou.or.jp/english/index.htm, 067 to A.A., the Practical Research Project for Rare/Intractable Diseases from the Japan Agency for Medical Research and Development, AMED http://www.amed.go.jp/en/program/list/01/05/016.html, 15AeK0109047h0002 to A.A., and the Smoking Research Foundation; http://www.srf.or.jp/english/index.html, 1848 to A.A.