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Inhibitory Effects of Quercetin and Its Main Methyl, Sulfate, and Glucuronic Acid Conjugates on Cytochrome P450 Enzymes, and on OATP, BCRP and MRP2 Transporters

Quercetin is a flavonoid, its glycosides and aglycone are found in significant amounts in several plants and dietary supplements. Because of the high presystemic biotransformation of quercetin, mainly its conjugates appear in circulation. As has been reported in previous studies, quercetin can inter...

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Autores principales: Mohos, Violetta, Fliszár-Nyúl, Eszter, Ungvári, Orsolya, Kuffa, Katalin, Needs, Paul W., Kroon, Paul A., Telbisz, Ágnes, Özvegy-Laczka, Csilla, Poór, Miklós
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7468908/
https://www.ncbi.nlm.nih.gov/pubmed/32751996
http://dx.doi.org/10.3390/nu12082306
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author Mohos, Violetta
Fliszár-Nyúl, Eszter
Ungvári, Orsolya
Kuffa, Katalin
Needs, Paul W.
Kroon, Paul A.
Telbisz, Ágnes
Özvegy-Laczka, Csilla
Poór, Miklós
author_facet Mohos, Violetta
Fliszár-Nyúl, Eszter
Ungvári, Orsolya
Kuffa, Katalin
Needs, Paul W.
Kroon, Paul A.
Telbisz, Ágnes
Özvegy-Laczka, Csilla
Poór, Miklós
author_sort Mohos, Violetta
collection PubMed
description Quercetin is a flavonoid, its glycosides and aglycone are found in significant amounts in several plants and dietary supplements. Because of the high presystemic biotransformation of quercetin, mainly its conjugates appear in circulation. As has been reported in previous studies, quercetin can interact with several proteins of pharmacokinetic importance. However, the interactions of its metabolites with biotransformation enzymes and drug transporters have barely been examined. In this study, the inhibitory effects of quercetin and its most relevant methyl, sulfate, and glucuronide metabolites were tested on cytochrome P450 (CYP) (2C19, 3A4, and 2D6) enzymes as well as on organic anion-transporting polypeptides (OATPs) (OATP1A2, OATP1B1, OATP1B3, and OATP2B1) and ATP (adenosine triphosphate) Binding Cassette (ABC) (BCRP and MRP2) transporters. Quercetin and its metabolites (quercetin-3′-sulfate, quercetin-3-glucuronide, isorhamnetin, and isorhamnetin-3-glucuronide) showed weak inhibitory effects on CYP2C19 and 3A4, while they did not affect CYP2D6 activity. Some of the flavonoids caused weak inhibition of OATP1A2 and MRP2. However, most of the compounds tested proved to be strong inhibitors of OATP1B1, OATP1B3, OATP2B1, and BCRP. Our data demonstrate that not only quercetin but some of its conjugates, can also interact with CYP enzymes and drug transporters. Therefore, high intake of quercetin may interfere with the pharmacokinetics of drugs.
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spelling pubmed-74689082020-09-04 Inhibitory Effects of Quercetin and Its Main Methyl, Sulfate, and Glucuronic Acid Conjugates on Cytochrome P450 Enzymes, and on OATP, BCRP and MRP2 Transporters Mohos, Violetta Fliszár-Nyúl, Eszter Ungvári, Orsolya Kuffa, Katalin Needs, Paul W. Kroon, Paul A. Telbisz, Ágnes Özvegy-Laczka, Csilla Poór, Miklós Nutrients Article Quercetin is a flavonoid, its glycosides and aglycone are found in significant amounts in several plants and dietary supplements. Because of the high presystemic biotransformation of quercetin, mainly its conjugates appear in circulation. As has been reported in previous studies, quercetin can interact with several proteins of pharmacokinetic importance. However, the interactions of its metabolites with biotransformation enzymes and drug transporters have barely been examined. In this study, the inhibitory effects of quercetin and its most relevant methyl, sulfate, and glucuronide metabolites were tested on cytochrome P450 (CYP) (2C19, 3A4, and 2D6) enzymes as well as on organic anion-transporting polypeptides (OATPs) (OATP1A2, OATP1B1, OATP1B3, and OATP2B1) and ATP (adenosine triphosphate) Binding Cassette (ABC) (BCRP and MRP2) transporters. Quercetin and its metabolites (quercetin-3′-sulfate, quercetin-3-glucuronide, isorhamnetin, and isorhamnetin-3-glucuronide) showed weak inhibitory effects on CYP2C19 and 3A4, while they did not affect CYP2D6 activity. Some of the flavonoids caused weak inhibition of OATP1A2 and MRP2. However, most of the compounds tested proved to be strong inhibitors of OATP1B1, OATP1B3, OATP2B1, and BCRP. Our data demonstrate that not only quercetin but some of its conjugates, can also interact with CYP enzymes and drug transporters. Therefore, high intake of quercetin may interfere with the pharmacokinetics of drugs. MDPI 2020-07-31 /pmc/articles/PMC7468908/ /pubmed/32751996 http://dx.doi.org/10.3390/nu12082306 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
Mohos, Violetta
Fliszár-Nyúl, Eszter
Ungvári, Orsolya
Kuffa, Katalin
Needs, Paul W.
Kroon, Paul A.
Telbisz, Ágnes
Özvegy-Laczka, Csilla
Poór, Miklós
Inhibitory Effects of Quercetin and Its Main Methyl, Sulfate, and Glucuronic Acid Conjugates on Cytochrome P450 Enzymes, and on OATP, BCRP and MRP2 Transporters
title Inhibitory Effects of Quercetin and Its Main Methyl, Sulfate, and Glucuronic Acid Conjugates on Cytochrome P450 Enzymes, and on OATP, BCRP and MRP2 Transporters
title_full Inhibitory Effects of Quercetin and Its Main Methyl, Sulfate, and Glucuronic Acid Conjugates on Cytochrome P450 Enzymes, and on OATP, BCRP and MRP2 Transporters
title_fullStr Inhibitory Effects of Quercetin and Its Main Methyl, Sulfate, and Glucuronic Acid Conjugates on Cytochrome P450 Enzymes, and on OATP, BCRP and MRP2 Transporters
title_full_unstemmed Inhibitory Effects of Quercetin and Its Main Methyl, Sulfate, and Glucuronic Acid Conjugates on Cytochrome P450 Enzymes, and on OATP, BCRP and MRP2 Transporters
title_short Inhibitory Effects of Quercetin and Its Main Methyl, Sulfate, and Glucuronic Acid Conjugates on Cytochrome P450 Enzymes, and on OATP, BCRP and MRP2 Transporters
title_sort inhibitory effects of quercetin and its main methyl, sulfate, and glucuronic acid conjugates on cytochrome p450 enzymes, and on oatp, bcrp and mrp2 transporters
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7468908/
https://www.ncbi.nlm.nih.gov/pubmed/32751996
http://dx.doi.org/10.3390/nu12082306
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