Rutin reduces colonic damage, expression of COX-2 and iNOS, and mRNA expression of IL-6 on DSS-induced experimental chronic ulcerative colitis.

RM Giner-Pons, M Marin, E Giner-Ventura, MC Recio, JL Ríos. University of Valencia, Pharmacology, 46100, Spain

Introduction. Although the physiological inflammatory process is beneficial for a host’s response, an aberrant resolution and prolonged inflammatory state is often associated with chronic inflammatory diseases such as inflammatory bowel disease (IBD). One of the two major forms of IBD is ulcerative colitis (UC) (Pan et al. 2010). So far, many types of treatment for UC have been developed, but additional therapeutic approaches are needed due to the ineffectiveness and side effects of conventional therapies. In the past few years, special interest has been given to phenolic compounds as potential drugs for the treatment of UC (Kwon et al., 2005). Among the natural bioactive compounds found in the diet, rutin has been shown to exert multiple pharmacological activities, including antibacterial, antitumor, and anti-inflammatory activity, among others (Janbaz et al., 2001). While its anti-inflammatory activity on acute experimental models of UC has been reported (Kwon et al., 2005), no studies about its effect on a persistent chronic inflammatory response have been developed. Herein, we report on rutin’s protective effect against chronic DSS-induced ulcerative colitis in an experimental model.

Experimental Approach. Female C57BL/6 mice weighing 19-22 g were randomly assigned to three groups (water, DSS, and DSS + rutin-treated groups) of 7-10 animals each who received four 7-day cycles of DSS. In each DSS cycle mice were allowed free access to tap water supplemented by 1% DSS in the two first cycles and 2% DSS in the following two cycles, as well as free access to food. In the treated group, the food was supplemented with 0.5% rutin. A week without DSS was interleaved between DSS cycles. The water group was allowed to free access to drinking water and food without supplements. Body weight, food, and fluid intake were monitored three times a week. After eight weeks of treatment, the mice were killed by cervical dislocation and their colons were removed and submitted for macroscopic examination. The disease activity index score (DAI) was checked, taking weight loss, stool blood, and rectal bleeding into account. Several pro-inflammatory mediators were determined with the aid of biochemical assays, PCR, and Western blot analysis. Statistical significance was determined by analysis of variance (ANOVA) and Dunnet’t test.

Key results and discussion. Rutin treatment significantly reduced the colonic weight/length ratio by 50% (p<0.01) and improved the extent and severity of injury by 81% (p<0.01), compared with the untreated colitic group. It also significantly down-regulated the expression of the pro-inflammatory enzymes COX-2 and iNOS by 90% (p<0.01) and 52% (p<0.01), respectively, and reduced colonic mRNA expression of IL-6 by 30% (p<0.01). Since oxidative stress has been implicated in the pathogenesis of DSS-induced colitis through its oxidative damage on DNA (Pan et al., 2011), this may constitute a pathway through which rutin can exert its anti-inflammatory effects (Abdel-Raheem et. al., 2010). The results suggest the effectiveness of rutin in the treatment of IBD pathogenesis, which could represent a novel target for future therapies in chronic UC.

Acknowledgement. Spanish Government, MICIIN (SAF 2009-13059-C03-01).

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