Protective effects of β-casofensin, a bioactive peptide from bovine β-casein, against indomethacin-induced intestinal lesions in rats

Mol Nutr Food Res. 2016 Apr;60(4):823-33. doi: 10.1002/mnfr.201500680. Epub 2016 Feb 3.

Abstract

Scope: β-casofensin, also known as peptide β-CN(94-123), is a milk bioactive peptide that modulates the intestinal barrier through its action on goblet cells. Here, we evaluated whether oral administration of β-casofensin can prevent indomethacin-induced injury of the jejunum in rats.

Methods and results: Rats received β-casofensin (0.01-100 μM) or tap water by daily gavage (4 μL/g) for eight days, then two subcutaneous injections of indomethacin (10 mg/kg, days 9 and 10) and were euthanized on day 12. In vitro, we investigated the effects of β-casofensin on the restitution of a wounded monolayer. Preventive administration of β-casofensin (100 μM) reduced intestinal macroscopic and microscopic damage induced by indomethacin. β-casofensin also prevented the depletion of goblet cells and increased myeloperoxidase activity, as well as tumor necrosis factor-ɑ (TNF-ɑ) expression and immunostaining of active caspase-3 in the jejunum of rats treated with indomethacin. In wound healing experiments, β-casofensin promoted epithelial restitution with no effect on cell proliferation. This effect was inhibited by pre-incubation with an anti-CC chemokine receptor 6 (CCR6) neutralizing antibody.

Conclusions: β-casofensin exerts protective effects in indomethacin-induced enteritis through preservation of goblet cells and improvement in wound healing. β-casofensin could therefore become vital in nutritional programs for the prevention of intestinal diseases.

Keywords: Functional food; Inflammatory bowel disease; Intestinal protection; Milk bioactive peptide; Mucus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Animals
  • Caseins / chemistry*
  • Caseins / pharmacology*
  • Cattle
  • Enteritis / chemically induced
  • Enteritis / prevention & control
  • HT29 Cells / drug effects
  • Humans
  • Indomethacin / adverse effects*
  • Intestinal Mucosa / drug effects
  • Intestinal Mucosa / pathology
  • Intestines / drug effects*
  • Intestines / pathology
  • Jejunal Diseases / chemically induced
  • Jejunal Diseases / prevention & control
  • Male
  • Peptide Fragments / administration & dosage
  • Peptide Fragments / chemistry
  • Peptide Fragments / pharmacology*
  • Protective Agents / pharmacology
  • Rats, Wistar
  • Wound Healing / drug effects*

Substances

  • Caseins
  • Peptide Fragments
  • Protective Agents
  • beta-casofensin
  • Indomethacin