title: Dietary rutin, but not its aglycone quercetin, ameliorates dextran sulfate sodium-induced experimental colitis in mice: attenuation of pro-inflammatory gene expression.
abstract: 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)-1 beta in both colonic mucosa and peritoneal macrophages was quantified by enzyme-linked immunosorbent assay. Further, mRNA expression levels of IL-1 beta, tumor necrosis factor-alpha, IL-6, granulocyte macrophage-colony stimulating factor, inducible nitric oxide synthase, and cyclooxygenase (COX)-1 and 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-1 beta levels were blunted significantly in rutin-, but not quercetin-, fed mice (P<0.01), while dietary rutin attenuated the expressions of IL-1 beta 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-1 beta levels (P<0.01). Notably, a 0.1% rutin diet given 3 days after DSS treatment significantly suppressed both colorectal shortening and IL-1 beta 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.
authors.affiliation: Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Kyoto 606-8502, Japan.
authors.forename: Ki Han
authors.initials: KH
authors.lastname: Kwon
authors.forename: Akira
authors.initials: A
authors.lastname: Murakami
authors.forename: Takuji
authors.initials: T
authors.lastname: Tanaka
authors.forename: Hajime
authors.initials: H
authors.lastname: Ohigashi
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003092:Colitis / Q000188:drug therapy* / Q000473:pathology; D016264:Dextran Sulfate / Q000494:pharmacology; D004032:Diet; D005260:Female; D015870:Gene Expression; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy*; D007375:Interleukin-1 / Q000096:biosynthesis / Q000235:genetics*; D015850:Interleukin-6 / Q000096:biosynthesis; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D008813:Mice, Inbred ICR; D011794:Quercetin / Q000008:administration & dosage*; D012431:Rutin / Q000008:administration & dosage*
chemical_list: D007375:Interleukin-1; D015850:Interleukin-6; D012431:Rutin; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D016264:Dextran Sulfate; D011794:Quercetin