Biotransformation of Flavokawains A, B, and C, Chalcones from Kava (Piper methysticum), by Human Liver Microsomes

Katharina Zenger, Sara Agnolet, Bernd Schneider, Birgit Kraus

12 Citations (Scopus)

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.

Original languageEnglish
JournalJournal of Agricultural and Food Chemistry
Volume63
Issue number28
Pages (from-to)6376-85
Number of pages10
ISSN0021-8561
DOIs
Publication statusPublished - 22 Jul 2015

Keywords

  • Chalcone/analogs & derivatives
  • Chalcones/metabolism
  • Flavonoids
  • Glucuronides/metabolism
  • Humans
  • Kava/chemistry
  • Microsomes, Liver/metabolism
  • Uridine Diphosphate Glucuronic Acid/metabolism

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