Regioselective and stereospecific glucuronidation of trans- and cis-resveratrol in human.
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.
Aumont
V
V
Groupe d'Etude des Substances Naturelles à Intérêt Thérapeutique (EA 491), Université Victor Segalen Bordeaux 2, Bordeaux, France.
Krisa
S
S
Battaglia
E
E
Netter
P
P
Richard
T
T
Mérillon
J M
JM
Magdalou
J
J
Sabolovic
N
N
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000378:metabolism*; D020723:Glucuronic Acid / Q000378:metabolism*; D014453:Glucuronosyltransferase / Q000378:metabolism; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D008862:Microsomes, Liver / Q000201:enzymology / Q000378:metabolism*; D008968:Molecular Conformation; D011994:Recombinant Proteins / Q000378:metabolism; D000077185:Resveratrol; D013267:Stilbenes / Q000378:metabolism*; D000090264:UDP-Glucuronosyltransferase 1A9; D000099148:UGT1A1 Enzyme
D000894:Anti-Inflammatory Agents, Non-Steroidal; D020723:Glucuronic Acid; D014453:Glucuronosyltransferase; D011994:Recombinant Proteins; D000077185:Resveratrol; D013267:Stilbenes; D000090264:UDP-Glucuronosyltransferase 1A9; D000099148:UGT1A1 Enzyme; C000715591:UGT1A9 protein, human; C110655:UDP-glucuronosyltransferase, UGT1A6