title: Biotransformation of Flavokawains A, B, and C, Chalcones from Kava (Piper methysticum), by Human Liver Microsomes.
abstract: The in vitro metabolism of flavokawains A, B, and C (FKA, FKB, FKC), methoxylated chalcones from Piper methysticum, was examined using human liver microsomes. Phase I metabolism and phase II metabolism (glucuronidation) as well as combined phase I+II metabolism were studied. For identification and structure elucidation of microsomal metabolites, LC-HRESIMS and NMR techniques were applied. Major phase I metabolites were generated by demethylation in position C-4 or C-4' and hydroxylation predominantly in position C-4, yielding FKC as phase I metabolite of FKA and FKB, helichrysetin as metabolite of FKA and FKC, and cardamonin as metabolite of FKC. To an even greater extent, flavokawains were metabolized in the presence of uridine diphosphate (UDP) glucuronic acid by microsomal UDP-glucuronosyl transferases. For all flavokawains, monoglucuronides (FKA-2'-O-glucuronide, FKB-2'-O-glucuronide, FKC-2'-O-glucuronide, FKC-4-O-glucuronide) were found as major phase II metabolites. The dominance of generated glucuronides suggests a role of conjugated chalcones as potential active compounds in vivo.
authors.affiliation: †Pharmaceutical Biology, Institute of Pharmacy, University of Regensburg, Universitätsstraße 31, 93053 Regensburg, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Zenger
authors.affiliation: §Max-Planck-Institute for Chemical Ecology, Beutenberg Campus, Hans-Knöll-Straße 8, 07745 Jena, Germany.
authors.forename: Sara
authors.initials: S
authors.lastname: Agnolet
authors.affiliation: §Max-Planck-Institute for Chemical Ecology, Beutenberg Campus, Hans-Knöll-Straße 8, 07745 Jena, Germany.
authors.forename: Bernd
authors.initials: B
authors.lastname: Schneider
authors.affiliation: †Pharmaceutical Biology, Institute of Pharmacy, University of Regensburg, Universitätsstraße 31, 93053 Regensburg, Germany.
authors.forename: Birgit
authors.initials: B
authors.lastname: Kraus
mesh_terms: D002599:Chalcone / Q000031:analogs & derivatives; D047188:Chalcones / Q000378:metabolism*; D005419:Flavonoids; D020719:Glucuronides / Q000378:metabolism; D006801:Humans; D020901:Kava / Q000737:chemistry*; D008862:Microsomes, Liver / Q000378:metabolism*; D014535:Uridine Diphosphate Glucuronic Acid / Q000378:metabolism
chemical_list: D047188:Chalcones; D005419:Flavonoids; D020719:Glucuronides; C500809:flavokawain A; C452039:flavokawain B; D014535:Uridine Diphosphate Glucuronic Acid; D002599:Chalcone
keywords: Piper methysticum; cardamonin; flavokawain; glucuronides; human liver microsomes; kava; metabolism