Abstract
Ferulic acid is a secondary metabolite usually found as esters in plants and dihydrocaffeic acid results from the microbial metabolism of flavonoids and of caffeic acid, both widely distributed in food. Even though ferulic acid and flavonoids have been proposed to exert several beneficial effects on health, their in vivo activities could partly result from their microbial metabolites and strongly depend on their bioavailability. The absorption and metabolism of phenolic acids were studied in vitro with a model for the colonic epithelium composed of absorptive and mucus secreting cells, ex vivo with everted colonic sacs and liver slices, and in vivo with rats. The photoprotective effect of phenolic acids was tested in vitro on the keratinocytes HaCaT. The ferulic acid permeation was mainly by transcellular diffusion and also by a facilitated transport (S-MCT and MCT1). Intestinal cells conjugated ferulic acid with sulphate or glucuronide and reduced its unsaturated side chain. In rats, intestinal cells were more potent for glucuronidation of dihydrocaffeic acid, whereas the liver favoured sulphation, the methylation being regio-selective. Intestinal and hepatic cells oxidized dihydroferulic acid into ferulic acid, which they reduced into dihydroferulic acid. HaCaT cells were able of sulphation, methylation and reduction. Dihydrocaffeic acid decreased the cytotoxicity and the production of IL-6 and IL-8 in HaCaT cells following UV radiation, the minimum structure required for such effect consisting in a propionic side chain attached to a phenyl ring substituted with a catechol moiety. Dihydrocaffeic acid also protected erythrocytes from lysis induced by a free radical initiator. Phenolic acids released from food by the colonic microflora can be conjugated and metabolized by the intestinal epithelium, liver and other tissues, such as the epidermis, strongly reducing the circulating amount of the parent compound, which could be the most active form.