Protective effect of ellagic acid, a natural polyphenolic compound, in a murine model of Crohn's disease

Biochem Pharmacol. 2011 Oct 1;82(7):737-45. doi: 10.1016/j.bcp.2011.06.043. Epub 2011 Jul 7.


Current epidemiological and experimental studies support a beneficial role of dietary polyphenols in several gastrointestinal diseases, including inflammatory bowel disease. The aim of this study was to gain a better understanding of the effects of a naturally occurring polyphenol, ellagic acid, present in some fruits such as pomegranate, raspberries and nuts among others, in an experimental murine model of Crohn's disease by intra-colonic administration of TNBS in rats. Analysis of the lesions were carried out by macroscopic and histological technics. Inflammation response was assessed by histology and myeloperoxidase activity. iNOS and COX-2 are upregulated by MAPKs and NF-κB nuclear transcription factor in intestinal epithelial cells thus, we determined the expression of iNOS, COX-2 and the involvement of the p38, JNK, ERK1/2 MAPKs and NF-κB signalling in the protective effect of EA by western blotting. Oral administration of EA (10-20 mg/kg) diminished the severity and extension of the intestinal injuries induced by TNBS although there was no observed a significant dose-response. In addition, EA increased mucus production in goblet cells in colon mucosa, decreased neutrophil infiltration and pro-inflammatory proteins COX-2 and iNOS overexpression. Also EA was capable of reducing the activation of p38, JNK and ERK1/2 MAPKs, preventing the inhibitory protein IκB-degradation and inducing an inhibition of the nuclear translocation level of p65 in colonic mucosa. In conclusion, EA reduces the damage in a rat model of Crohn's disease, alleviates the oxidative events and returns pro-inflammatory proteins expression to basal levels probably through MAPKs and NF-κB signalling pathways.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Active Transport, Cell Nucleus
  • Acute Disease
  • Animals
  • Cell Nucleus / metabolism
  • Colon / drug effects
  • Colon / metabolism
  • Crohn Disease / chemically induced
  • Crohn Disease / pathology
  • Crohn Disease / prevention & control*
  • Cyclooxygenase 2 / metabolism
  • Ellagic Acid / therapeutic use*
  • Flavonoids / therapeutic use*
  • I-kappa B Kinase / metabolism
  • Intestinal Mucosa / drug effects
  • Intestinal Mucosa / metabolism
  • Leukocytes / physiology
  • Male
  • Mitogen-Activated Protein Kinases / metabolism
  • Nitric Oxide Synthase Type II / metabolism
  • Peroxidase / metabolism
  • Phenols / therapeutic use*
  • Phosphorylation
  • Polyphenols
  • Rats
  • Rats, Wistar
  • Signal Transduction
  • Transcription Factor RelA / metabolism
  • Transcriptional Activation
  • Trinitrobenzenesulfonic Acid


  • Flavonoids
  • Phenols
  • Polyphenols
  • Rela protein, rat
  • Transcription Factor RelA
  • Ellagic Acid
  • Trinitrobenzenesulfonic Acid
  • Peroxidase
  • Nitric Oxide Synthase Type II
  • Cyclooxygenase 2
  • I-kappa B Kinase
  • Mitogen-Activated Protein Kinases