title: Increased CYP4B1 mRNA is associated with the inhibition of dextran sulfate sodium-induced colitis by caffeic acid in mice.
abstract: Susceptibility to inflammatory bowel diseases depends upon interactions between the genetics of the individual and induction of chronic mucosal inflammation. We hypothesized that administration of dietary phenolics, caffeic acid and rutin, would suppress upregulation of inflammatory markers and intestinal damage in a mouse model of colitis. Colitis was induced in C3H/ HeOuJ mice (8 weeks old, 6 male/6 female per treatment) with 1.25% dextran sulfate sodium (DSS) for 6 d in their drinking water. Rutin (1.0 mmol (524 mg)/kg in diet), caffeic acid (1.0 mmol (179 mg)/kg in diet), and hypoxoside extract (15 mg/d, an anticolitic phenolic control) were fed to the mice for 7 d before and during DSS treatment, as well as without DSS treatment. Body weight loss was prevented by rutin and caffeic acid during DSS treatment. Colon lengths in mice fed caffeic acid and hypoxoside during DSS treatment were similar to DSS-negative control. Food intake was improved and myeloperoxidase (MPO) was decreased with each phenolic treatment in DSS-treated mice compared with DSS treatment alone. Colonic mRNA expression of IL-17 and iNOS were inhibited when IL-4 was increased by each phenolic treatment combined with DSS, whereas CYP4B1 mRNA was increased only by caffeic acid in DSS-treated mice, compared with DSS treatment alone. Colonic and cecal histopathology scores of DSS-treated mice were significantly more severe (P < 0.01) than in mice fed caffeic acid before and during DSS treatment, based on mucosal height, necrosis, edema, erosion, and inflammatory cell infiltration. Although both rutin and caffeic acid suppressed the expression of selected inflammatory markers, only caffeic acid protected against DSS-induced colitis, in association with normalization of CYP4B1 expression. The inhibition of DSS-induced colitic pathology by caffeic acid was mediated by mechanisms in addition to anti-inflammatory effects that deserve further study.
authors.affiliation: The Iowa State University, Department of Food Science and Human Nutrition, 224D MacKay, Ames, IA 50011, USA.
authors.forename: Zhong
authors.initials: Z
authors.lastname: Ye
authors.forename: Zhiping
authors.initials: Z
authors.lastname: Liu
authors.forename: Abigail
authors.initials: A
authors.lastname: Henderson
authors.forename: Kwangwon
authors.initials: K
authors.lastname: Lee
authors.forename: Jesse
authors.initials: J
authors.lastname: Hostetter
authors.forename: Michael
authors.initials: M
authors.lastname: Wannemuehler
authors.forename: Suzanne
authors.initials: S
authors.lastname: Hendrich
mesh_terms: D000480:Alkynes / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001189:Aryl Hydrocarbon Hydroxylases / Q000096:biosynthesis*; D001835:Body Weight / Q000187:drug effects; D002109:Caffeic Acids / Q000494:pharmacology*; D003092:Colitis / Q000139:chemically induced / Q000201:enzymology* / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*; D003106:Colon / Q000201:enzymology / Q000473:pathology; D016264:Dextran Sulfate / Q000633:toxicity*; D004435:Eating / Q000187:drug effects; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D005960:Glucosides / Q000494:pharmacology; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000201:enzymology / Q000235:genetics / Q000517:prevention & control; D020381:Interleukin-17 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D008297:Male; D051379:Mice; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis; D009929:Organ Size / Q000187:drug effects; D009195:Peroxidase / Q000096:biosynthesis; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000235:genetics; D012431:Rutin / Q000494:pharmacology; D013997:Time Factors
chemical_list: D000480:Alkynes; D000975:Antioxidants; D002109:Caffeic Acids; D005960:Glucosides; D020381:Interleukin-17; D012333:RNA, Messenger; D015847:Interleukin-4; D012431:Rutin; C087941:hypoxoside; D016264:Dextran Sulfate; D009195:Peroxidase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D001189:Aryl Hydrocarbon Hydroxylases; C095029:cytochrome P-450 CYP4B1; C040048:caffeic acid