title: Microsomal hydroxylation and glucuronidation of [6]-gingerol.
abstract: [6]-Gingerol is the major pungent principle of ginger and frequently is ingested with various condiments and nutritional supplements. We report here that incubation of [6]-gingerol with NADPH-fortified rat hepatic microsomes gave rise to eight metabolites, which were tentatively identified by GC-MS analysis as two products of aromatic hydroxylation as well as the diastereomers of two aliphatic hydroxylation products and the diastereomers of [6]-gingerdiol. Hepatic microsomes from rats and humans fortified with UDPGA glucuronidated [6]-gingerol predominantly at the phenolic hydroxyl group, but small amounts of a second monoglucuronide involving the aliphatic hydroxyl group were also identified by LC-MS/MS analysis. Human intestinal microsomes formed the phenolic glucuronide only. Supersomes containing human UGT1A1 and 1A3 exclusively generated the phenolic glucuronide, albeit with very low activities, whereas UGT1A9 catalyzed the specific formation of the alcoholic glucuronide and UGT2B7 the predominant formation of the phenolic glucuronide with high activities. Our study indicates a rather complex metabolism of [6]-gingerol, which should be taken into consideration for the multiple biological activities of this compound.
authors.affiliation: Institute of Applied Biosciences, Chair of Food Chemistry, University of Karlsruhe, P.O. Box 6980, D-76128 Karlsruhe, Germany.
authors.forename: Erika
authors.initials: E
authors.lastname: Pfeiffer
authors.forename: Franziska F
authors.initials: FF
authors.lastname: Heuschmid
authors.forename: Stefan
authors.initials: S
authors.lastname: Kranz
authors.forename: Manfred
authors.initials: M
authors.lastname: Metzler
mesh_terms: D000818:Animals; D002396:Catechols; D005233:Fatty Alcohols / Q000378:metabolism*; D020719:Glucuronides / Q000378:metabolism; D014453:Glucuronosyltransferase / Q000378:metabolism; D006801:Humans; D006900:Hydroxylation; D007527:Isoenzymes / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism; D008875:Middle Aged; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D002396:Catechols; D005233:Fatty Alcohols; D020719:Glucuronides; D007527:Isoenzymes; C007845:gingerol; D014453:Glucuronosyltransferase