title: In vitro metabolism of jaceosidin and characterization of cytochrome P450 and UDP-glucuronosyltransferase enzymes in human liver microsomes.
abstract: Jaceosidin is an active component in Artemisia species as well as Eupatorium species and it exhibits antiallergic, anticancer, antioxidant, anti-inflammatory, and antimutagenic activities. Jaceosidin was metabolized to jaceosidin glucuronide, 6-O-desmethyljaceosidin, hydroxyjaceosidin, 6-O-desmethyljaceosidin glucuronide, and hydroxyjaceosidin glucuronide in human liver microsomes. This study characterized the human liver cytochrome P450 (CYP) and UDPglucuronosyltransferase (UGT) enzymes responsible for the metabolism of jaceosidin. CYP1A2 was identified as the major enzyme responsible for the formation of 6-O-desmethyljaceosidin and hydroxyjaceosidin from jaceosidin on the basis of a combination of correlation analysis and experiments including immuno-inhibition, chemical inhibition in human liver microsomes, and metabolism by human cDNA-expressed CYP enzymes. Jaceosidin glucuronidation was catalyzed by UGT1A1, UGT1A3, UGT1A7, UGT1A8, UGT1A9, and UGT1A10. These results suggest that the pharmacokinetics of jaceosidin may be dramatically affected by polymorphic CYP1A2, UGT1A1, and UGT1A7 responsible for the metabolism of jaceosidin or by the coadministration of relevant CYP1A2 or UGT inhibitors or inducers.
authors.affiliation: Drug Metabolism & Bioanalysis Laboratory, College of Pharmacy, Wonkwang University, Iksan 570-749, Korea.
authors.forename: Won Young
authors.initials: WY
authors.lastname: Song
authors.forename: Hye Young
authors.initials: HY
authors.lastname: Ji
authors.forename: Nam-In
authors.initials: NI
authors.lastname: Baek
authors.forename: Tae-Sook
authors.initials: TS
authors.lastname: Jeong
authors.forename: Hye Suk
authors.initials: HS
authors.lastname: Lee
mesh_terms: D019306:Artemisia; D019388:Cytochrome P-450 CYP1A2 / Q000378:metabolism; D065609:Cytochrome P-450 CYP1A2 Inhibitors; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D005419:Flavonoids / Q000378:metabolism* / Q000493:pharmacokinetics; D014453:Glucuronosyltransferase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006801:Humans; D008862:Microsomes, Liver / Q000201:enzymology* / Q000378:metabolism; D035261:Plant Components, Aerial; D028321:Plant Preparations / Q000378:metabolism* / Q000493:pharmacokinetics*
chemical_list: D065609:Cytochrome P-450 CYP1A2 Inhibitors; D065607:Cytochrome P-450 Enzyme Inhibitors; D005419:Flavonoids; D028321:Plant Preparations; C477508:jaceosidin; D003577:Cytochrome P-450 Enzyme System; D019388:Cytochrome P-450 CYP1A2; D014453:Glucuronosyltransferase