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Identification of Human Sulfotransferases Active towards Silymarin Flavonolignans and Taxifolin

Natural phenolic compounds are known to be metabolized by phase II metabolic reactions. In this study, we examined the in vitro sulfation of the main constituents of silymarin, an herbal remedy produced from the fruits of the milk thistle. The study focused on major flavonolignan constituents, inclu...

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Autores principales: Vrba, Jiří, Papoušková, Barbora, Kosina, Pavel, Lněničková, Kateřina, Valentová, Kateřina, Ulrichová, Jitka
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7465014/
https://www.ncbi.nlm.nih.gov/pubmed/32806559
http://dx.doi.org/10.3390/metabo10080329
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author Vrba, Jiří
Papoušková, Barbora
Kosina, Pavel
Lněničková, Kateřina
Valentová, Kateřina
Ulrichová, Jitka
author_facet Vrba, Jiří
Papoušková, Barbora
Kosina, Pavel
Lněničková, Kateřina
Valentová, Kateřina
Ulrichová, Jitka
author_sort Vrba, Jiří
collection PubMed
description Natural phenolic compounds are known to be metabolized by phase II metabolic reactions. In this study, we examined the in vitro sulfation of the main constituents of silymarin, an herbal remedy produced from the fruits of the milk thistle. The study focused on major flavonolignan constituents, including silybin A, silybin B, isosilybin A, isosilybin B, silychristin, and silydianin, as well as the flavonoid taxifolin. Using ultra-high-performance liquid chromatography coupled with tandem mass spectrometry (UHPLC-MS), individual flavonolignans and taxifolin were found to be sulfated by human liver and human intestinal cytosols. Moreover, experiments with recombinant enzymes revealed that human sulfotransferases (SULTs) 1A1*1, 1A1*2, 1A2, 1A3, 1B1, 1C4, and 1E1 catalyzed the sulfation of all of the tested compounds, with the exception of silydianin, which was not sulfated by SULT1B1 and SULT1C4. The sulfation products detected were monosulfates, of which some of the major ones were identified as silybin A 20-O-sulfate, silybin B 20-O-sulfate, and isosilybin A 20-O-sulfate. Further, we also observed the sulfation of the tested compounds when they were tested in the silymarin mixture. Sulfates of flavonolignans and of taxifolin were produced by incubating silymarin with all of the above SULT enzymes, with human liver and intestinal cytosols, and also with human hepatocytes, even though the spectrum and amount of the sulfates varied among the metabolic models. Considering our results and the expression patterns of human sulfotransferases in metabolic tissues, we conclude that flavonolignans and taxifolin can potentially undergo both intestinal and hepatic sulfation, and that SULTs 1A1, 1A3, 1B1, and 1E1 could be involved in the biotransformation of the constituents of silymarin.
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spelling pubmed-74650142020-09-04 Identification of Human Sulfotransferases Active towards Silymarin Flavonolignans and Taxifolin Vrba, Jiří Papoušková, Barbora Kosina, Pavel Lněničková, Kateřina Valentová, Kateřina Ulrichová, Jitka Metabolites Article Natural phenolic compounds are known to be metabolized by phase II metabolic reactions. In this study, we examined the in vitro sulfation of the main constituents of silymarin, an herbal remedy produced from the fruits of the milk thistle. The study focused on major flavonolignan constituents, including silybin A, silybin B, isosilybin A, isosilybin B, silychristin, and silydianin, as well as the flavonoid taxifolin. Using ultra-high-performance liquid chromatography coupled with tandem mass spectrometry (UHPLC-MS), individual flavonolignans and taxifolin were found to be sulfated by human liver and human intestinal cytosols. Moreover, experiments with recombinant enzymes revealed that human sulfotransferases (SULTs) 1A1*1, 1A1*2, 1A2, 1A3, 1B1, 1C4, and 1E1 catalyzed the sulfation of all of the tested compounds, with the exception of silydianin, which was not sulfated by SULT1B1 and SULT1C4. The sulfation products detected were monosulfates, of which some of the major ones were identified as silybin A 20-O-sulfate, silybin B 20-O-sulfate, and isosilybin A 20-O-sulfate. Further, we also observed the sulfation of the tested compounds when they were tested in the silymarin mixture. Sulfates of flavonolignans and of taxifolin were produced by incubating silymarin with all of the above SULT enzymes, with human liver and intestinal cytosols, and also with human hepatocytes, even though the spectrum and amount of the sulfates varied among the metabolic models. Considering our results and the expression patterns of human sulfotransferases in metabolic tissues, we conclude that flavonolignans and taxifolin can potentially undergo both intestinal and hepatic sulfation, and that SULTs 1A1, 1A3, 1B1, and 1E1 could be involved in the biotransformation of the constituents of silymarin. MDPI 2020-08-12 /pmc/articles/PMC7465014/ /pubmed/32806559 http://dx.doi.org/10.3390/metabo10080329 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Vrba, Jiří
Papoušková, Barbora
Kosina, Pavel
Lněničková, Kateřina
Valentová, Kateřina
Ulrichová, Jitka
Identification of Human Sulfotransferases Active towards Silymarin Flavonolignans and Taxifolin
title Identification of Human Sulfotransferases Active towards Silymarin Flavonolignans and Taxifolin
title_full Identification of Human Sulfotransferases Active towards Silymarin Flavonolignans and Taxifolin
title_fullStr Identification of Human Sulfotransferases Active towards Silymarin Flavonolignans and Taxifolin
title_full_unstemmed Identification of Human Sulfotransferases Active towards Silymarin Flavonolignans and Taxifolin
title_short Identification of Human Sulfotransferases Active towards Silymarin Flavonolignans and Taxifolin
title_sort identification of human sulfotransferases active towards silymarin flavonolignans and taxifolin
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7465014/
https://www.ncbi.nlm.nih.gov/pubmed/32806559
http://dx.doi.org/10.3390/metabo10080329
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