Resveratrol is efficiently glucuronidated by UDP-glucuronosyltransferases in the human gastrointestinal tract and in Caco-2 cells.
Resveratrol (3, 5, 4'-trihydroxy-trans-stilbene), a natural polyphenol present in grapes and peanuts, has been reported to exert a variety of potentially therapeutic effects. The aim of this study was to determine the contribution of the gastrointestinal (GI) tract to the glucuronidation of this compound and its cis-isomer, which also occurs naturally. For this purpose, glucuronidation of the two resveratrol isomers was investigated in human microsomes prepared from: stomach, duodenum, four segments of the remaining small intestine (S-1 to S-4) and colon, and from the human intestinal cell lines Caco-2 and PD-7. cis- and trans-Resveratrol were efficiently glucuronidated in the GI tract with the formation of both 3-O- and 4'-O-glucuronides, however, the two stereoisomers were glucuronidated at different rates depending on the donor and the segment considered. Microsomes prepared from Caco-2 and PD-7 cells also efficiently glucuronidated cis-resveratrol and, to a lesser extent, the trans-isomer, however, only the 3-O-glucuronide was formed. Among the UDP-glucuronosyltransferases (UGT) that are known to be expressed in the GI tract, the isoforms UGT1A1, 1A6, 1A8, 1A9 and 1A10 were active in glucuronidating trans- and/or cis-resveratrol. The results demonstrate that the GI tract may contribute significantly to the first pass metabolism of these naturally occurring polyphenols.
Sabolovic
Nicole
N
UMR 7561 CNRS-Université Henri Poincaré, Nancy I, Faculté de Médecine, Vandoeuvre-lès-Nancy, France. Nicole.Sabolovic@medecine.uhp-nancy.fr
Humbert
Anne-Claude
AC
Radominska-Pandya
Anna
A
Magdalou
Jacques
J
D018938:Caco-2 Cells; D041981:Gastrointestinal Tract / Q000378:metabolism*; D020719:Glucuronides / Q000032:analysis / Q000378:metabolism*; D014453:Glucuronosyltransferase / Q000378:metabolism*; D006801:Humans; D008099:Liver / Q000378:metabolism; D008861:Microsomes / Q000378:metabolism; D000077185:Resveratrol; D013267:Stilbenes / Q000378:metabolism*
D020719:Glucuronides; D013267:Stilbenes; D014453:Glucuronosyltransferase; D000077185:Resveratrol