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.