Regioselective and stereospecific glucuronidation of trans- and cis-resveratrol in human

Arch Biochem Biophys. 2001 Sep 15;393(2):281-9. doi: 10.1006/abbi.2001.2496.

Abstract

Resveratrol (3,5,4'-trihydroxy-trans-stilbene) is a polyphenol present in wine, which has been reported to have anti-inflammatory, anti-platelet, and anti-carcinogenic effects. The glucuronidation of this compound and that of the cis-isomer also naturally present, has been investigated in human liver microsomes. Both isomers were actively glucuronidated. The reaction led to the formation of two glucuronides (3-O- and 4'-O-glucuronides), whose structure was characterized by LC-MS and proton NMR. Glucuronidation was regio- and stereoselective. It occurred at a faster rate with the cis-isomer and preferred the 3-position on both isomers. In addition, the glucuronidation of resveratrol was tested using several recombinant UDP-glucuronosyltransferase (UGT) isoforms. The reaction was catalyzed by UGT of the family 1A (UGT1A1, 1A6, 1A7, 1A9, 1A10). The bilirubin conjugating UGT1A1 was mainly involved in the 3-O-glucuronidation of trans-resveratrol, whereas the phenol conjugating UGT1A6 activity was restricted to cis-resveratrol. The UGT1A9 and 1A10 were active toward both isomers. The activity supported by UGT2B7 and UGT2B15 was very low and restricted to cis-resveratrol. UGT1A3, 1A4, 2B4, and 2B11 were unable to form resveratrol glucuronides.

MeSH terms

  • Anti-Inflammatory Agents, Non-Steroidal / metabolism*
  • Glucuronic Acid / metabolism*
  • Glucuronosyltransferase / metabolism
  • Humans
  • Magnetic Resonance Spectroscopy
  • Mass Spectrometry
  • Microsomes, Liver / enzymology
  • Microsomes, Liver / metabolism*
  • Molecular Conformation
  • Recombinant Proteins / metabolism
  • Resveratrol
  • Stilbenes / metabolism*

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Recombinant Proteins
  • Stilbenes
  • Glucuronic Acid
  • UDP-glucuronosyltransferase, UGT1A6
  • UGT1A1 enzyme
  • Glucuronosyltransferase
  • UDP-glucuronosyltransferase 1A9
  • Resveratrol