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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doaj-1ee985e2775b4627b977898e85dc39662020-11-25T03:46:39ZengMDPI AGMetabolites2218-19892020-08-011032932910.3390/metabo10080329Identification of Human Sulfotransferases Active towards Silymarin Flavonolignans and TaxifolinJiří Vrba0Barbora Papoušková1Pavel Kosina2Kateřina Lněničková3Kateřina Valentová4Jitka Ulrichová5Department of Medical Chemistry and Biochemistry, Faculty of Medicine and Dentistry, Palacký University, Hněvotínská 3, 77515 Olomouc, Czech RepublicRegional Centre of Advanced Technologies and Materials, Department of Analytical Chemistry, Faculty of Science, Palacký University, 17. Listopadu 12, 77146 Olomouc, Czech RepublicDepartment of Medical Chemistry and Biochemistry, Faculty of Medicine and Dentistry, Palacký University, Hněvotínská 3, 77515 Olomouc, Czech RepublicDepartment of Medical Chemistry and Biochemistry, Faculty of Medicine and Dentistry, Palacký University, Hněvotínská 3, 77515 Olomouc, Czech RepublicLaboratory of Biotransformation, Institute of Microbiology of the Czech Academy of Sciences, Vídeňská 1083, 14220 Prague, Czech RepublicDepartment of Medical Chemistry and Biochemistry, Faculty of Medicine and Dentistry, Palacký University, Hněvotínská 3, 77515 Olomouc, Czech RepublicNatural 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-<i>O</i>-sulfate, silybin B 20-<i>O</i>-sulfate, and isosilybin A 20-<i>O</i>-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.https://www.mdpi.com/2218-1989/10/8/329silybinsilychristinsilydianinisosilybindihydroquercetinmetabolism |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Jiří Vrba Barbora Papoušková Pavel Kosina Kateřina Lněničková Kateřina Valentová Jitka Ulrichová |
spellingShingle |
Jiří Vrba Barbora Papoušková Pavel Kosina Kateřina Lněničková Kateřina Valentová Jitka Ulrichová Identification of Human Sulfotransferases Active towards Silymarin Flavonolignans and Taxifolin Metabolites silybin silychristin silydianin isosilybin dihydroquercetin metabolism |
author_facet |
Jiří Vrba Barbora Papoušková Pavel Kosina Kateřina Lněničková Kateřina Valentová Jitka Ulrichová |
author_sort |
Jiří Vrba |
title |
Identification of Human Sulfotransferases Active towards Silymarin Flavonolignans and Taxifolin |
title_short |
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_sort |
identification of human sulfotransferases active towards silymarin flavonolignans and taxifolin |
publisher |
MDPI AG |
series |
Metabolites |
issn |
2218-1989 |
publishDate |
2020-08-01 |
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-<i>O</i>-sulfate, silybin B 20-<i>O</i>-sulfate, and isosilybin A 20-<i>O</i>-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. |
topic |
silybin silychristin silydianin isosilybin dihydroquercetin metabolism |
url |
https://www.mdpi.com/2218-1989/10/8/329 |
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