Intestinal anti-inflammatory effects of goat whey on DNBS-induced colitis in mice

PLoS One. 2017 Sep 28;12(9):e0185382. doi: 10.1371/journal.pone.0185382. eCollection 2017.

Abstract

This study evaluated the intestinal anti-inflammatory effects of goat whey in a mouse model of colitis induced by 2,4-dinitrobenzenesulfonic acid that resembles human IBD. At a concentration of 4 g/kg/day, the goat whey improved the symptoms of intestinal inflammation, namely by decreasing the disease activity index, colonic weight/length, and leukocyte infiltration. Moreover, goat whey inhibited NF-κB p65 and p38 MAPK signaling pathways and consequently down-regulated the gene expression of various proinflammatory markers such as IL-1β, IL-6, IL-17, TNF-α, iNOS, MMP-9, ICAM-1. Also, goat whey increased the expression of proteins such as mucins, occludin proteins and cytokine signalling suppressors. The immunomodulatory properties of goat whey were also evaluated in vitro using the murine macrophage cell line Raw 264 and CMT-93 cells derived from mouse rectum carcinomas. The results revealed the ability of goat whey to inhibit the production of NO and reduce IL-6 production in LPS-stimulated cells. In conclusion, goat whey exhibited anti-inflammatory effects in the DNBS model of intestinal inflammation, and these observations were confirmed by its immunomodulatory properties in vitro. Together, our results indicate that goat whey could have applications for the treatment of IBD.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Anti-Inflammatory Agents / therapeutic use*
  • Colitis / chemically induced*
  • Colitis / genetics
  • Colitis / pathology*
  • Cytokines / genetics
  • Cytokines / metabolism
  • Dinitrofluorobenzene / analogs & derivatives
  • Disease Models, Animal
  • Enzyme-Linked Immunosorbent Assay
  • Fluorescent Antibody Technique
  • Gene Expression Regulation / drug effects
  • Goats
  • Inflammation Mediators / metabolism
  • Intestinal Mucosa / drug effects
  • Intestinal Mucosa / pathology
  • Intestines / drug effects
  • Intestines / pathology*
  • Male
  • Mice
  • RAW 264.7 Cells
  • Real-Time Polymerase Chain Reaction
  • Whey / chemistry*

Substances

  • Anti-Inflammatory Agents
  • Cytokines
  • Inflammation Mediators
  • 2,4-dinitrofluorobenzene sulfonic acid
  • Dinitrofluorobenzene

Grants and funding

The authors are grateful to the Conselho Nacional de Desenvolvimento Científico e Tecnológico—CNPq for funding the research, the Laboratory Food Chemistry—UFPB, Brazil, for drying the goat whey, the Federal University of Rio Grande do Norte for technical-scientific support, the Junta de Andalucia (CTS 164) and the Spanish Ministry of Economy and Competitiveness (AGL2015-67995-C3-3-R) with funds from the European Union. A. Rodriguez-Nogales and F. Algieri are postdoctoral fellows at the University of Granada; M.E. Rodriguez-Cabezas is a postdoctoral fellow at the CIBER-EHD. The CIBER-EHD is funded by the Instituto de Salud Carlos III.