In Vitro Liver Metabolism of Six Flavonoid C-Glycosides

Several medical plants belonging to the genera Passiflora, Viola, and Crataegus accumulate flavonoid C-glycosides, which likely contribute to their efficacy. Information regarding their phase I and II metabolism in the liver are lacking. Thus,...

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Autores principales:	Martina Tremmel, Christian Paetz, Jörg Heilmann
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	flavonoid C-glycosides liver metabolism S9 fraction human liver microsomes Organic chemistry QD241-441
Acceso en línea:	https://doaj.org/article/63db81cc00fd46c3a198e9319bc8ee02
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spelling	oai:doaj.org-article:63db81cc00fd46c3a198e9319bc8ee022021-11-11T18:36:09ZIn Vitro Liver Metabolism of Six Flavonoid C-Glycosides10.3390/molecules262166321420-3049https://doaj.org/article/63db81cc00fd46c3a198e9319bc8ee022021-11-01T00:00:00Zhttps://www.mdpi.com/1420-3049/26/21/6632https://doaj.org/toc/1420-3049Several medical plants belonging to the genera <i>Passiflora</i>, <i>Viola</i>, and <i>Crataegus</i> accumulate flavonoid C-glycosides, which likely contribute to their efficacy. Information regarding their phase I and II metabolism in the liver are lacking. Thus, in vitro liver metabolism of orientin, isoorientin, schaftoside, isoschaftoside, vitexin, and isovitexin, all of which accumulated in <i>Passiflora incarnata</i> L., was investigated by incubation in subcellular systems with human liver microsomes and human liver S9 fraction. All metabolite profiles were comprehensively characterized using HPLC-DAD and UHPLC–MS/MS analysis. Mono-glycosylic flavones of the luteolin-type orientin and isoorientin showed a broad range of mono-glucuronidated and mono-sulfated metabolites, whereas for mono-glycosylic flavones of the apigenin-type vitexin and isovitexin, only mono-glucuronidates could be detected. For di-glycosylic flavones of the apigenin-type schaftosid and isoschaftosid, no phase I or II metabolites were identified. The main metabolite of isoorientin was isolated using solid-phase extraction and prep. HPLC-DAD and identified as isoorientin-3′-<i>O</i>-α-glucuronide by NMR analysis. A second isolated glucuronide was assigned as isoorientin 4′-<i>O</i>-α-glucuronide. These findings indicate that vitexin and isovitexin are metabolized preferentially by uridine 5′-diphospho glucuronosyltransferases (UGTs) in the liver. As only orientin and isoorientin showed mono-sulfated and mono-glucuronidated metabolites, the dihydroxy group in 3′,4′-position may be essential for additional sulfation by sulfotransferases (SULTs) in the liver. The diglycosylic flavones schaftoside and isoschaftoside are likely not accepted as substrates of the used liver enzymes under the chosen conditions.Martina TremmelChristian PaetzJörg HeilmannMDPI AGarticleflavonoid C-glycosidesliver metabolismS9 fractionhuman liver microsomesOrganic chemistryQD241-441ENMolecules, Vol 26, Iss 6632, p 6632 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	flavonoid C-glycosides liver metabolism S9 fraction human liver microsomes Organic chemistry QD241-441
spellingShingle	flavonoid C-glycosides liver metabolism S9 fraction human liver microsomes Organic chemistry QD241-441 Martina Tremmel Christian Paetz Jörg Heilmann In Vitro Liver Metabolism of Six Flavonoid C-Glycosides
description	Several medical plants belonging to the genera <i>Passiflora</i>, <i>Viola</i>, and <i>Crataegus</i> accumulate flavonoid C-glycosides, which likely contribute to their efficacy. Information regarding their phase I and II metabolism in the liver are lacking. Thus, in vitro liver metabolism of orientin, isoorientin, schaftoside, isoschaftoside, vitexin, and isovitexin, all of which accumulated in <i>Passiflora incarnata</i> L., was investigated by incubation in subcellular systems with human liver microsomes and human liver S9 fraction. All metabolite profiles were comprehensively characterized using HPLC-DAD and UHPLC–MS/MS analysis. Mono-glycosylic flavones of the luteolin-type orientin and isoorientin showed a broad range of mono-glucuronidated and mono-sulfated metabolites, whereas for mono-glycosylic flavones of the apigenin-type vitexin and isovitexin, only mono-glucuronidates could be detected. For di-glycosylic flavones of the apigenin-type schaftosid and isoschaftosid, no phase I or II metabolites were identified. The main metabolite of isoorientin was isolated using solid-phase extraction and prep. HPLC-DAD and identified as isoorientin-3′-<i>O</i>-α-glucuronide by NMR analysis. A second isolated glucuronide was assigned as isoorientin 4′-<i>O</i>-α-glucuronide. These findings indicate that vitexin and isovitexin are metabolized preferentially by uridine 5′-diphospho glucuronosyltransferases (UGTs) in the liver. As only orientin and isoorientin showed mono-sulfated and mono-glucuronidated metabolites, the dihydroxy group in 3′,4′-position may be essential for additional sulfation by sulfotransferases (SULTs) in the liver. The diglycosylic flavones schaftoside and isoschaftoside are likely not accepted as substrates of the used liver enzymes under the chosen conditions.
format	article
author	Martina Tremmel Christian Paetz Jörg Heilmann
author_facet	Martina Tremmel Christian Paetz Jörg Heilmann
author_sort	Martina Tremmel
title	In Vitro Liver Metabolism of Six Flavonoid C-Glycosides
title_short	In Vitro Liver Metabolism of Six Flavonoid C-Glycosides
title_full	In Vitro Liver Metabolism of Six Flavonoid C-Glycosides
title_fullStr	In Vitro Liver Metabolism of Six Flavonoid C-Glycosides
title_full_unstemmed	In Vitro Liver Metabolism of Six Flavonoid C-Glycosides
title_sort	in vitro liver metabolism of six flavonoid c-glycosides
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/63db81cc00fd46c3a198e9319bc8ee02
work_keys_str_mv	AT martinatremmel invitrolivermetabolismofsixflavonoidcglycosides AT christianpaetz invitrolivermetabolismofsixflavonoidcglycosides AT jorgheilmann invitrolivermetabolismofsixflavonoidcglycosides
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In Vitro Liver Metabolism of Six Flavonoid C-Glycosides

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