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

• Published in: Pharmacological research 2012-09, Vol.66 (3), p.235-242
• Main Authors: Rosillo, Maria Angeles, Sánchez-Hidalgo, Marina, Cárdeno, Ana, Aparicio-Soto, Marina, Sánchez-Fidalgo, Susana, Villegas, Isabel, de la Lastra, Catalina Alarcón
• Format: Article
• Language: English
• Subjects: Animal models; Animals; Anti-Inflammatory Agents - chemistry; Anti-Inflammatory Agents - pharmacology; Antioxidants; c-Jun amino-terminal kinase; Colitis; Colitis - chemically induced; Colitis - drug therapy; Colitis - metabolism; Colitis - pathology; Colon - drug effects; Colon - metabolism; Colon - pathology; COX-2; Crohn Disease - drug therapy; Crohn Disease - metabolism; Crohn Disease - pathology; Cyclooxygenase 2 - metabolism; Cyclooxygenase-2; Dietary Supplements; Disease Models, Animal; Ellagic acid; Ellagic Acid - pharmacology; I-kappa B Proteins - metabolism; Inflammatory bowel diseases; Injuries; Interferon-alpha - metabolism; Intestinal Mucosa - drug effects; Intestinal Mucosa - metabolism; Intestinal Mucosa - pathology; Male; MAP kinase; MAP Kinase Kinase 4 - metabolism; MAP Kinase Signaling System - drug effects; NF- Kappa B protein; NF-kappa B - metabolism; NF-KappaB Inhibitor alpha; Nitric Oxide Synthase Type II - metabolism; Nitric-oxide synthase; Nuclear transport; p38 Mitogen-Activated Protein Kinases - metabolism; Peroxidase - metabolism; Phosphorylation - drug effects; Plant Extracts - pharmacokinetics; Polyphenols; Polyphenols - pharmacology; Pomegranate; Punica granatum; Punicaceae - chemistry; Rats; Rats, Wistar; Signal Transduction - drug effects; TNBS-induced colitis; TNF-α; Trinitrobenzenesulfonic Acid - adverse effects; Western blotting
• ISSN: 1043-6618; 1096-1186
• DOI: 10.1016/j.phrs.2012.05.006

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 250mg/kg/day, (iii) PE 500mg/kg/day, (iv) EA 10mg/kg/day and (v) EA 10mg/kg/day enriched-PE 250mg/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).