Quercitrin, 3-rhamnosylquercetin, is a flavonoid that exerts antiinflammatory activity in experimental colitis (Sanchez de Medina et al., 1996). The present study investigates the mechanisms involved in this effect. Colitis was induced in female Wistar rats (170-190 g) by incorporating dextran sulfate sodium (DSS) in drinking water at 5% (w/v) during 5 days and at 2% (w/v) for the following 10 days. One group of animals (n=10) was treated orally with quercitrin (1 mg/kg/day) dissolved in distilled water (4 ml/kg), starting when DSS concentration was changed. A DSS control group (n=10) and a non-colitic group (n=10) were also included for reference. All animals were sacrificed 15 days after. The colonic inflammatory status was evaluated microscopically, on a 0 to 30 scale, (Stucchi et al., 2000), and biochemically: total glutathione content, NOS activity (Rodriguez-Cabezas et al., 2002) and NF-B activity (Renard et al., 2001). Colonic iNOS expression was also evaluated by immunoblotting. in vitro experiments were also performed in primary cultures of murine bone marrow derived macrophages (BMDM) (Comalada et al., 2003) stimulated with LPS (100 ng/ml) to study the effects of quercitrin and quercetin on iNOS expression and NF-B activation by Western blot. Data were expressed as mean ± S.E.M. Differences among means were tested for statistical significance using one-way analysis of variance (ANOVA) and post hoc least significance tests.

analysis of the specimens revealed that the flavonoid reduced the histological score from 12.4 ± 2.8 in the control group to 5.7 ± 1.9 (p<0.05). Quercitrin counteracted colonic glutathione depletion (1762 ± 67 vs. 1517 ± 49 nmol/g tissue in control group; p<0.01), and inhibited colonic NOS activity (74.4 ± 7.0 vs. 97.8 ± 6.1 pmol citrulline/mg protein in controls; p<0.05). An inhibition in colonic iNOS expression was also observed (Figure 1A). In addition, a significant reduction in colonic activated NF-B levels was obtained after quercitrin treatment (57554 ± 7650 vs. 85158 ± 4429 arbitrary units in control group; p<0.05). in vitro experiments revealed that quercetin (50 mM), but not quercitrin, inhibited both iNOS expression (Figure 1B) and NF-B activation (Figure 1C) in LPS-stimulated BMDM.

In conclusion, the intestinal antiinflammatory effect of quercitrin was associated with an improvement on intestinal oxidative stress and with downregulation of colonic NOS activity via inhibition of NF-B signalling pathway.

Comalada M et al. (2003) J Immunol 170: 4450-6.
Renard P et al. (2001) Nucleic Acids Res 29: e21.
Rodriguez-Cabezas et al. (2002) J Nutr 132: 3263-71.
Sanchez de Medina F et al. (1996) J Pharm Exp Ther 278:771-9.
Stucchi AF et al. (2000) Am J Physiol 279: G1298-306.