Dietary supplementation of an ellagic acid-enriched pomegranate extract attenuates chronic colonic inflammation in rats

Pharmacol Res. 2012 Sep;66(3):235-42. doi: 10.1016/j.phrs.2012.05.006. Epub 2012 Jun 4.

Abstract

Dietary polyphenols present in Punica granatum (pomegranate), such as ellagitannins and ellagic acid (EA) have shown to exert anti-inflammatory and antioxidant properties. This study was designed to evaluate the effects of a dietary EA-enriched pomegranate extract (PE) in a murine chronic model of Cronh's disease (CD). Colonic injury was induced by intracolonic instillation of trinitrobenzensulfonic acid (TNBS). Rats were fed with different diets during 30 days before TNBS instillation and 2 weeks before killing: (i) standard, (ii) PE 250 mg/kg/day, (iii) PE 500 mg/kg/day, (iv) EA 10 mg/kg/day and (v) EA 10 mg/kg/day enriched-PE 250 mg/kg/day. Inflammation response was assessed by histology and MPO activity and TNF-α production. Besides, colonic expressions of iNOS, COX-2, p38, JNK, pERK1/2 MAPKs, IKBα and nuclear p65 NF-κB were studied by western blotting. MPO activity and the TNF-α levels were significantly reduced in dietary fed rats when compared with TNBS group. Similarly, PE and an EA-enriched PE diets drastically decreased COX-2 and iNOS overexpression, reduced MAPKs phosporylation and prevented the nuclear NF-κB translocation. Dietary supplementation of EA contributes in the beneficial effect of PE in this experimental colitis model and may be a novel therapeutic strategy to manage inflammatory bowel disease (IBD).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / chemistry
  • Anti-Inflammatory Agents / pharmacology*
  • Colitis / chemically induced
  • Colitis / drug therapy*
  • Colitis / metabolism
  • Colitis / pathology
  • Colon / drug effects
  • Colon / metabolism
  • Colon / pathology
  • Crohn Disease / drug therapy
  • Crohn Disease / metabolism
  • Crohn Disease / pathology
  • Cyclooxygenase 2 / metabolism
  • Dietary Supplements
  • Disease Models, Animal
  • Ellagic Acid / pharmacology*
  • I-kappa B Proteins / metabolism
  • Interferon-alpha / metabolism
  • Intestinal Mucosa / drug effects
  • Intestinal Mucosa / metabolism
  • Intestinal Mucosa / pathology
  • Lythraceae / chemistry*
  • MAP Kinase Kinase 4 / metabolism
  • MAP Kinase Signaling System / drug effects
  • Male
  • NF-KappaB Inhibitor alpha
  • NF-kappa B / metabolism
  • Nitric Oxide Synthase Type II / metabolism
  • Peroxidase / metabolism
  • Phosphorylation / drug effects
  • Plant Extracts / pharmacokinetics*
  • Polyphenols / pharmacology
  • Rats
  • Rats, Wistar
  • Signal Transduction / drug effects
  • Trinitrobenzenesulfonic Acid / adverse effects
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • Anti-Inflammatory Agents
  • I-kappa B Proteins
  • Interferon-alpha
  • NF-kappa B
  • Nfkbia protein, rat
  • Plant Extracts
  • Polyphenols
  • NF-KappaB Inhibitor alpha
  • Ellagic Acid
  • Trinitrobenzenesulfonic Acid
  • Peroxidase
  • Nitric Oxide Synthase Type II
  • Nos2 protein, rat
  • Cyclooxygenase 2
  • Ptgs2 protein, rat
  • p38 Mitogen-Activated Protein Kinases
  • MAP Kinase Kinase 4