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- W2318555430 abstract "Chalcones possess a broad spectrum of biological activities and a high potential for therapeutic application. Although pharmacological properties of chalcones are extensively investigated, little is known about their absorption, bioavailability, and metabolism in general. Flavokawain A, B and C (FKA, FKB, FKC) are naturally occuring chalcones, that have been isolated from Piper methysticum Forst. (Piperaceae) and show anti-inflammatory and anti-cancer activity [1]. In vitro metabolism of FKA, FKB and FKC was investigated using human liver microsomes. Different microsomal incubation systems were used to study both phase I and phase II (glucuronidation) metabolism as well as combined phase I+II metabolism. Metabolites were identified by LC-HRESIMS and exact accordance to the retention times of the references in the chromatographic system. In phase I metabolism, demethylation in position C-4 or C-4' and hydroxylation predominantly in position C-4 occured. This lead to the formation of FKC as major phase I metabolite of FKA. FKC and alpinetin chalcone were found as major phase I metabolites of FKB. Helichrysetin and OH-FKC represented the major phase I metabolites of FKC. The compounds were even more extensively metabolized in presence of uridine diphosphate (UDP) glucuronic acid by microsomal UDP-glucuronosyltransferases. For all test chalcones, the corresponding monoglucuronides were detected as the major metabolites in phase II and combined metabolism. A metabolic profile of investigated chalcones is proposed. The predominance of glucuronides over phase I metabolites generally emphasizes the important role of conjugated chalcones metabolites as possible in vivo active principles." @default.
- W2318555430 created "2016-06-24" @default.
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- W2318555430 date "2014-10-30" @default.
- W2318555430 modified "2023-10-18" @default.
- W2318555430 title "In vitro metabolism of flavokawains from Piper methysticum using human liver microsomes" @default.
- W2318555430 doi "https://doi.org/10.1055/s-0034-1394873" @default.
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