Transport and Metabolism of Ferulic Acid through the Colonic Epithelium

Abstract

ABSTRACT:Ferulic acid is an important antioxidant found in food, beverages, supplements, and herbal medicines. However, its mechanism of absorption in the colon has never been examined, even though this is its main site of in vivo absorption. Ferulic acid was efficiently transported as the free form through an in vitro model for the colonic epithelium consisting of cocultured Caco-2 and mucusproducing HT29-MTX cells, with only a small amount transported as feruloyl-glucuronide or sulfate, together with some free dihydroferulic acid. This pattern of metabolism and permeation was also seen with the use of rat everted ascending and descending colon sacs. In the cell model, free ferulic acid permeated by passive diffusion, as judged by the linearity of the uptake over time and nonsaturable concentration dependence. The permeation was independent of tight junctions but strongly linked to the hydrophobicity of the different phenolic acids tested, suggesting a transcellular rather than a paracellular transport. Using inhibitors, we showed that only a small proportion (<20%) of the free ferulic acid transport was carrier-mediated. The production of metabolites in the basal chamber was lowered by 3-[[3-[2-(7-chloroquinolin-2-yl)-vinyl]phenyl]-(2-dimethylcarbamoylethylsulfanyl)methylsulfanyl] propionic acid (MK571) and increased by cyclosporin A, implying an involvement of multidrug resistance protein and P-glycoprotein transporters in the efflux of metabolites, respectively to the serosal and luminal sides. These results show that the form of ferulic acid available to the blood after passage across the colonic barrier would be mainly the free form, together with only a small percentage of conjugated and reduced ferulic acid.

Impact of dose on the bioavailability of coffee chlorogenic acids in humans

“…Most ferulic acid passes across the small intestine in the unmodified, unconjugated aglycone form, 17 implying that phase II sulphation of the hydroxycinnamate occurs mainly in the liver.…”

Effect of edible oils on quercetin, kaempferol and galangin transport and conjugation in the intestinal Caco-2/HT29-MTX co-culture model

“…The system has been used previously to examine metabolism of phenolics, where the metabolism of ferulic acid is mainly by sulphation both in vivo 22 and in the co-cultured cellular system 17 . These conjugation properties are due to the distribution and expression of conjugating enzyme isoforms.…”

“…Co-cultured cells were grown for 21 days in 10% FBS supplemented medium as above which was changed every other day. The mucus was detected using Periodic Acid-Schiff's/Alcian-Blue staining protocol as described elsewhere 17 .…”

“…Prior to the experiments, the culture medium was replaced by fresh medium for at least [12][13][14][15][16][17][18][19][20][21][22][23][24] hours. Transport experiments were carried out with transport buffer solution consisting of HBSS supplemented with 1.8 mM CaCl 2 (to maintain integrity of the tight junction) and 100 µM ascorbic acid (to minimise degradation of flavonols).…”

Inhibition of hydroxycinnamic acid sulfation by flavonoids and their conjugated metabolites

“…Human studies and in vitro mechanistic studies showed that hydroxycinnamic acids are predominantly sulfated in the intestine and liver [1][2][3][4][5][6].…”