title: Protective effect of ellagic acid, a natural polyphenolic compound, in a murine model of Crohn's disease.
abstract: 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.
authors.affiliation: Department of Pharmacology, Faculty of Pharmacy, University of Seville, Profesor García González Street 2, 41012 Seville, Spain.
authors.forename: M A
authors.initials: MA
authors.lastname: Rosillo
authors.forename: M
authors.initials: M
authors.lastname: Sanchez-Hidalgo
authors.forename: A
authors.initials: A
authors.lastname: Cárdeno
authors.forename: C Alarcón
authors.initials: CA
authors.lastname: de la Lastra
mesh_terms: D021581:Active Transport, Cell Nucleus; D000208:Acute Disease; D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism; D003106:Colon / Q000187:drug effects / Q000378:metabolism; D003424:Crohn Disease / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D051546:Cyclooxygenase 2 / Q000378:metabolism; D004610:Ellagic Acid / Q000627:therapeutic use*; D005419:Flavonoids / Q000627:therapeutic use*; D051550:I-kappa B Kinase / Q000378:metabolism; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism; D007962:Leukocytes / Q000502:physiology; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism; D010636:Phenols / Q000627:therapeutic use*; D010766:Phosphorylation; D059808:Polyphenols; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction; D051996:Transcription Factor RelA / Q000378:metabolism; D015533:Transcriptional Activation; D014302:Trinitrobenzenesulfonic Acid
chemical_list: D005419:Flavonoids; D010636:Phenols; D059808:Polyphenols; C498145:Rela protein, rat; D051996:Transcription Factor RelA; D004610:Ellagic Acid; D014302:Trinitrobenzenesulfonic Acid; D009195:Peroxidase; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; D051550:I-kappa B Kinase; D020928:Mitogen-Activated Protein Kinases