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Inhibitory Effects of Quercetin and Its Human and Microbial Metabolites on Xanthine Oxidase Enzyme
Quercetin is an abundant flavonoid in nature and is used in several dietary supplements. Although quercetin is extensively metabolized by human enzymes and the colonic microflora, we have only few data regarding the pharmacokinetic interactions of its metabolites. Therefore, we investigated the inte...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6600370/ https://www.ncbi.nlm.nih.gov/pubmed/31159151 http://dx.doi.org/10.3390/ijms20112681 |
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author | Mohos, Violetta Pánovics, Attila Fliszár-Nyúl, Eszter Schilli, Gabriella Hetényi, Csaba Mladěnka, Přemysl Needs, Paul W. Kroon, Paul A. Pethő, Gábor Poór, Miklós |
author_facet | Mohos, Violetta Pánovics, Attila Fliszár-Nyúl, Eszter Schilli, Gabriella Hetényi, Csaba Mladěnka, Přemysl Needs, Paul W. Kroon, Paul A. Pethő, Gábor Poór, Miklós |
author_sort | Mohos, Violetta |
collection | PubMed |
description | Quercetin is an abundant flavonoid in nature and is used in several dietary supplements. Although quercetin is extensively metabolized by human enzymes and the colonic microflora, we have only few data regarding the pharmacokinetic interactions of its metabolites. Therefore, we investigated the interaction of human and microbial metabolites of quercetin with the xanthine oxidase enzyme. Inhibitory effects of five conjugates and 23 microbial metabolites were examined with 6-mercaptopurine and xanthine substrates (both at 5 μM), employing allopurinol as a positive control. Quercetin-3′-sulfate, isorhamnetin, tamarixetin, and pyrogallol proved to be strong inhibitors of xanthine oxidase. Sulfate and methyl conjugates were similarly strong inhibitors of both 6-mercaptopurine and xanthine oxidations (IC(50) = 0.2–0.7 μM); however, pyrogallol inhibited xanthine oxidation (IC(50) = 1.8 μM) with higher potency vs. 6-MP oxidation (IC(50) = 10.1 μM). Sulfate and methyl conjugates were approximately ten-fold stronger inhibitors (IC(50) = 0.2–0.6 μM) of 6-mercaptopurine oxidation than allopurinol (IC(50) = 7.0 μM), and induced more potent inhibition compared to quercetin (IC(50) = 1.4 μM). These observations highlight that some quercetin metabolites can exert similar or even a stronger inhibitory effect on xanthine oxidase than the parent compound, which may lead to the development of quercetin–drug interactions (e.g., with 6-mercaptopurin or azathioprine). |
format | Online Article Text |
id | pubmed-6600370 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-66003702019-07-16 Inhibitory Effects of Quercetin and Its Human and Microbial Metabolites on Xanthine Oxidase Enzyme Mohos, Violetta Pánovics, Attila Fliszár-Nyúl, Eszter Schilli, Gabriella Hetényi, Csaba Mladěnka, Přemysl Needs, Paul W. Kroon, Paul A. Pethő, Gábor Poór, Miklós Int J Mol Sci Article Quercetin is an abundant flavonoid in nature and is used in several dietary supplements. Although quercetin is extensively metabolized by human enzymes and the colonic microflora, we have only few data regarding the pharmacokinetic interactions of its metabolites. Therefore, we investigated the interaction of human and microbial metabolites of quercetin with the xanthine oxidase enzyme. Inhibitory effects of five conjugates and 23 microbial metabolites were examined with 6-mercaptopurine and xanthine substrates (both at 5 μM), employing allopurinol as a positive control. Quercetin-3′-sulfate, isorhamnetin, tamarixetin, and pyrogallol proved to be strong inhibitors of xanthine oxidase. Sulfate and methyl conjugates were similarly strong inhibitors of both 6-mercaptopurine and xanthine oxidations (IC(50) = 0.2–0.7 μM); however, pyrogallol inhibited xanthine oxidation (IC(50) = 1.8 μM) with higher potency vs. 6-MP oxidation (IC(50) = 10.1 μM). Sulfate and methyl conjugates were approximately ten-fold stronger inhibitors (IC(50) = 0.2–0.6 μM) of 6-mercaptopurine oxidation than allopurinol (IC(50) = 7.0 μM), and induced more potent inhibition compared to quercetin (IC(50) = 1.4 μM). These observations highlight that some quercetin metabolites can exert similar or even a stronger inhibitory effect on xanthine oxidase than the parent compound, which may lead to the development of quercetin–drug interactions (e.g., with 6-mercaptopurin or azathioprine). MDPI 2019-05-31 /pmc/articles/PMC6600370/ /pubmed/31159151 http://dx.doi.org/10.3390/ijms20112681 Text en © 2019 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 Pánovics, Attila Fliszár-Nyúl, Eszter Schilli, Gabriella Hetényi, Csaba Mladěnka, Přemysl Needs, Paul W. Kroon, Paul A. Pethő, Gábor Poór, Miklós Inhibitory Effects of Quercetin and Its Human and Microbial Metabolites on Xanthine Oxidase Enzyme |
title | Inhibitory Effects of Quercetin and Its Human and Microbial Metabolites on Xanthine Oxidase Enzyme |
title_full | Inhibitory Effects of Quercetin and Its Human and Microbial Metabolites on Xanthine Oxidase Enzyme |
title_fullStr | Inhibitory Effects of Quercetin and Its Human and Microbial Metabolites on Xanthine Oxidase Enzyme |
title_full_unstemmed | Inhibitory Effects of Quercetin and Its Human and Microbial Metabolites on Xanthine Oxidase Enzyme |
title_short | Inhibitory Effects of Quercetin and Its Human and Microbial Metabolites on Xanthine Oxidase Enzyme |
title_sort | inhibitory effects of quercetin and its human and microbial metabolites on xanthine oxidase enzyme |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6600370/ https://www.ncbi.nlm.nih.gov/pubmed/31159151 http://dx.doi.org/10.3390/ijms20112681 |
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