001P Granada Congress and Exhibitions Centre
6th European Congress of Pharmacology (EPHAR 2012)

 

 

Beneficial effects of an ellagic-enriched pomegranate extract on chronic TNBS-induced colitis in rats

MA Rosillo, M Sanchez-Hidalgo, A Cardeno, M Aparicio, M Conde, I Villegas, C Alarcon de la Lastra. Faculty of Pharmacy. University of Seville, Pharmacology 41012, Spain

 

Background and purpose: A complex system of intracellular signalling molecules, influences the uncontrolled immune system activation in inflammatory bowel disease (IBD). In previous studies, Punica granatum L. (pomegranate) has been shown to exert, antioxidant and anti-inflammatory effects. Besides, we have documented that Ellagic Acid (EA), a natural polyphenol compound present in pomegranate, decreased the degree of inflammation associated with chronic experimental colonic inflammation. To study the effects of a dietary EA-enriched pomegranate extract (PE) in a murine chronic model of CD. Experimental approach: Colonic injury was induced by intracolonic instillation of trinitrobenzenesulphonic acid (TNBS) (30mg/rat). Male Wistar rats were fed with diets : (1) standard diet (n=10), (2) PE 250 mg/kg/day (n=10) , (3) PE 500 mg/kg/day (n=10), (4) EA 10 mg/kg/day (n=10) and (5) EA 10 mg/kg/day enriched- PE 250 mg/kg/day (n=10) during 30 days before TNBS instillation and 2 weeks before killing. Inflammation response was assessed by MPO activity and TNF-α production. iNOS, COX- 2, p38, JNK, p-ERK1/2 MAPKs , IKBα inhibitory protein, and nuclear p65 NF-κB expressions were studied by western blotting in colon mucosa. The statistical significance was evaluated by one-way analysis of variance (ANOVA). Key results: MPO activity and the TNF-α levels were significantly reduced in dietary fed rats after TNBS administration (Table 1). Diets drastically decreased COX-2 and iNOS overexpression, reduced MAPKs activation, prevented the inhibitory protein (IκB-α) degradation as well as induced the nuclear p65 NF-κB downregulation. Conclusions and implications: 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 IBD.

Table 1

Group n MPO (U/mg tissue) n TNF-α (pg/mgtissue)
Sham
TNBS
PE 250
PE500
EA 10
PE+EA 		10
10
10
10
10
10 		0.51 ± 0.1
2.57 ± 0.2 ***
1.32 ± 0.19++
1.40 ± 0.14+++
1.05 ± 0.2+++
0.78 ± 0.19+++ 		10
10
10
10
10
10		 5.8 ± 0.9
14.7 ± 1.5 ***
7.90 ± 0.84++
6.70 ± 0.80+++
9.3 ± 0.93+
8.6 ± 0.3++

*** P<0.001, significantly different from Sham

+ P<0.05, ++ P<0.01 and +++ P<0.001, significantly different from TNBS.