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

M.A. Rosillo (1) , M. Sanchez-Hidalgo (1) , A. Cárdeno (1) , C. Alarcón de La Lastra (1)

1 Faculty of Pharmacy

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 (10-20mg/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.

Mots clés: Ellagic acid; TNBS; oxidative stress; COX-2; MAPK; NF-κB

Domaines: Pharmacologie

M.A. Rosillo, M. Sanchez-Hidalgo, A. Cárdeno, C. Alarcón de La Lastra. Protective effect of ellagic acid, a natural polyphenolic compound, in a murine model of Crohn's disease. Biochemical Pharmacology, 2011, 82 (7), pp.737. ⟨10.1016/j.bcp.2011.06.043⟩. ⟨hal-00723637⟩