| Phenolics, one category of micronutrients abundant in human diet, are believed to prevent some degenerative diseases such as cardiovascular diseases, digestive system diseases, and cancer. Numerous researchers have become increasingly interested in phenolics because of the recognition of the anti-inflammatory, antioxidant, anti-antiviral, and immune-stimulating properties of phenolics. In this dissertation, the overarching hypotheses were that plant phenolics were degraded by gut or oral microorganisms, influencing the absorption of these components; phenolics were transported by Caco-2 cell monolayers; and phenolic efficacy of colitic prevention depended on bioavailability. Our long-term goal is to elucidate the metabolism pattern of phenolics that may benefit colon health to prevent colitis. The first study, with in vitro anaerobic incubations for human fecal or mouse cecal samples, the degradation rates of major phenolics from Echinacea purpurea and Hypericum perforatum extracts were significantly different in both incubation methods. Caffeic acid was produced and one metabolite was generated during the metabolism of Echinacea extract. The second study with salivary bacterial incubation in vitro, 7-mixture compound oral degradation rates were statistically significant differences. Cluster analysis showed that significantly different groups of high and low degraders of caffeic acid and rutin were evident. In the third study with Caco-2 cell line, Hypericum perforatum components, chlorogenic acid, an ester of caffeic acic and quinic acid, quercetin, amentoflavone, and pseudohypericin were compared to test the apparent permeabilities from apical to basolateral transfer, the results demonstrated that the components had a low permeable ability after 4 h incubation with the monolayer. The fourth study in dextran sulfate sodium (DSS)-induced C3H/HeOuJ mouse colitis model, treated with caffeic acid compared with rutin (both of 1.0 mmol/kg in diet) and hypoxoside extract, only caffeic acid protected against DSS-induced colitic histopathological damage, in association with normalization of CYP4B1 expression. Finally, to examine interindividual variability in the efficacy of caffeic acid, the other strain, a CD-1/IGS mouse model was used with DSS-induced colitis. The expression of CYP4B1 was also increased by caffeic acid/DSS treatment. The main other findings showed that two significant different subgroups of caffeic acid and rutin were identified based upon cluster analysis of cecal histopathological score in mice fed caffeic acid/DSS. Caffeic acid-fed mice with severe cecal damage had significantly greater colonic MPO activity than did mice with mild cecal damage. Furthermore, the severe cecal damage subgroup was significantly associated with a lower plasma concentration of caffeic acid. These effects in mice fed caffeic acid/DSS were associated with the variety of caffeic acid bioavailability, probably due to gut microbial ecology, which is an important controllable variable in the effects of caffeic acid on colitis. |
