Transport and metabolism of ferulic acid through the colonic epithelium.
نویسندگان
چکیده
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 mucus-producing 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.
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عنوان ژورنال:
- Drug metabolism and disposition: the biological fate of chemicals
دوره 36 1 شماره
صفحات -
تاریخ انتشار 2008