Dietary rutin, but not its aglycone quercetin, ameliorates dextran sulfate sodium-induced experimental colitis in mice: attenuation of pro-inflammatory gene expression

Oxidative stress has been shown to play a pivotal role in the onset of inflammatory bowel disease (IBD) and carcinogenesis. We evaluated the effects of two dietary anti-oxidants, rutin and its aglycone quercetin, on dextran sulfate sodium (DSS)-induced experimental colitis in mice. Female ICR mice were fed a diet containing 0.1% rutin or 0.1% quercetin for 2 weeks, and given 5% DSS in drinking water during the second week to induce colitis. We also examined the dose-dependency of rutin and quercetin (0.01% and 0.001% each) as well as their therapeutic efficacy, which was evaluated following DSS administration, on DSS-induced colitis. The protein level of interleukin (IL)- 1beta in both colonic mucosa and peritoneal macrophages was quantified by enzyme-linked inummosorbent assay. Further, mRNA expression levels of IL-1beta, tumor necrosis factor-alpha, IL-6, granulocyte macrophage-colony stimulating factor, inducible nitric oxide synthase, and cyclooxygenase (COX)-1and COX-2 in colonic mucosa were determined by reverse transcription-polymerase chain reaction. A diet containing 0.1% rutin, but not quercetin, attenuated DSS-induced body weight loss and shortening of the colorectum (P < 0.01 and < 0.05, respectively), and dramatically improved colitis histological scores. Further, DSS-induced increases in colonic mucosal IL-1beta levels were blunted significantly in rutin-, but not quercetin-, fed mice (P < 0.01), while dietary rutin attenuated the expressions of IL-1beta and IL-6 mRNA in colonic mucosa (each, P < 0.01). As for dose dependency, 0.01 %, but not 0.001 %, dietary rutin significantly reduced mucosal IL-1beta levels (P < 0.01). Notably, a 0.1% rutin diet given 3 days after DSS treatment significantly suppressed both colorectal shortening and IL-1beta production (P < 0.05 and < 0.01, respectively). Dietary rutin ameliorates DSS-induced colitis, presumably by suppressing the induction of pro-inflammatory cytokines. Our results suggest that rutin may be useful for the prevention and treatment of IBD and colorectal carcinogenesis via attenuation of pro-inflammatory cytokine production. (C) 2004 Elsevier Inc. All rights reserved.