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...
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| Veröffentlicht in: | International journal of molecular sciences 2019-05, Vol.20 (11), p.2681 |
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| creator | Mohos, Violetta Pánovics, Attila Fliszár-Nyúl, Eszter Schilli, Gabriella Hetényi, Csaba Mladěnka, Přemysl Needs, Paul W Kroon, Paul A Pethő, Gábor Poór, Miklós |
| 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
= 0.2-0.7 μM); however, pyrogallol inhibited xanthine oxidation (IC
= 1.8 μM) with higher potency vs. 6-MP oxidation (IC
= 10.1 μM). Sulfate and methyl conjugates were approximately ten-fold stronger inhibitors (IC
= 0.2-0.6 μM) of 6-mercaptopurine oxidation than allopurinol (IC
= 7.0 μM), and induced more potent inhibition compared to quercetin (IC
= 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). |
| doi_str_mv | 10.3390/ijms20112681 |
| format | Article |
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= 0.2-0.7 μM); however, pyrogallol inhibited xanthine oxidation (IC
= 1.8 μM) with higher potency vs. 6-MP oxidation (IC
= 10.1 μM). Sulfate and methyl conjugates were approximately ten-fold stronger inhibitors (IC
= 0.2-0.6 μM) of 6-mercaptopurine oxidation than allopurinol (IC
= 7.0 μM), and induced more potent inhibition compared to quercetin (IC
= 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).</description><identifier>ISSN: 1422-0067</identifier><identifier>ISSN: 1661-6596</identifier><identifier>EISSN: 1422-0067</identifier><identifier>DOI: 10.3390/ijms20112681</identifier><identifier>PMID: 31159151</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>6-Mercaptopurine ; Allopurinol ; Azathioprine ; Chromatography ; Conjugates ; Dietary supplements ; Enzymes ; Flavonoids ; Granulocytes ; Inhibitors ; Metabolites ; Microflora ; Microorganisms ; Oxidation ; Pharmacology ; Pharmacy ; Quercetin ; Research parks ; Sulfates ; Uric acid ; Xanthine oxidase</subject><ispartof>International journal of molecular sciences, 2019-05, Vol.20 (11), p.2681</ispartof><rights>2019. This work is licensed under https://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2019 by the authors. 2019</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c478t-5f2fcb3becd3c4bf7259133ebb5b30f7b2a92c49ae2cdcbb51ef711557ce6d8b3</citedby><cites>FETCH-LOGICAL-c478t-5f2fcb3becd3c4bf7259133ebb5b30f7b2a92c49ae2cdcbb51ef711557ce6d8b3</cites><orcidid>0000-0002-8013-971X ; 0000-0002-6076-6900 ; 0000-0002-9805-6947</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6600370/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6600370/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31159151$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Mohos, Violetta</creatorcontrib><creatorcontrib>Pánovics, Attila</creatorcontrib><creatorcontrib>Fliszár-Nyúl, Eszter</creatorcontrib><creatorcontrib>Schilli, Gabriella</creatorcontrib><creatorcontrib>Hetényi, Csaba</creatorcontrib><creatorcontrib>Mladěnka, Přemysl</creatorcontrib><creatorcontrib>Needs, Paul W</creatorcontrib><creatorcontrib>Kroon, Paul A</creatorcontrib><creatorcontrib>Pethő, Gábor</creatorcontrib><creatorcontrib>Poór, Miklós</creatorcontrib><title>Inhibitory Effects of Quercetin and Its Human and Microbial Metabolites on Xanthine Oxidase Enzyme</title><title>International journal of molecular sciences</title><addtitle>Int J Mol Sci</addtitle><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
= 0.2-0.7 μM); however, pyrogallol inhibited xanthine oxidation (IC
= 1.8 μM) with higher potency vs. 6-MP oxidation (IC
= 10.1 μM). Sulfate and methyl conjugates were approximately ten-fold stronger inhibitors (IC
= 0.2-0.6 μM) of 6-mercaptopurine oxidation than allopurinol (IC
= 7.0 μM), and induced more potent inhibition compared to quercetin (IC
= 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).</description><subject>6-Mercaptopurine</subject><subject>Allopurinol</subject><subject>Azathioprine</subject><subject>Chromatography</subject><subject>Conjugates</subject><subject>Dietary supplements</subject><subject>Enzymes</subject><subject>Flavonoids</subject><subject>Granulocytes</subject><subject>Inhibitors</subject><subject>Metabolites</subject><subject>Microflora</subject><subject>Microorganisms</subject><subject>Oxidation</subject><subject>Pharmacology</subject><subject>Pharmacy</subject><subject>Quercetin</subject><subject>Research parks</subject><subject>Sulfates</subject><subject>Uric acid</subject><subject>Xanthine oxidase</subject><issn>1422-0067</issn><issn>1661-6596</issn><issn>1422-0067</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>8G5</sourceid><sourceid>BENPR</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNpdkUtrWzEQhUVJyHvXdRBkk0Wd6HEf1qZQgtsYEkwghe6EpDuKZe6VUkm3xP31UbAb3Kw0mvl0mKOD0GdKrjgX5NqthsQIpayZ0k_oiFaMTQhp2r2d-hAdp7QihHFWiwN0yCmtBa3pEdJzv3Ta5RDXeGYtmJxwsPhhhGggO4-V7_C8NG_HQW1u987EoJ3q8T1kpUPvMpRHHv9SPi-dB7x4cZ1KgGf-73qAU7RvVZ_gbHueoJ_fZ483t5O7xY_5zbe7ianaaZ7UllmjuQbTcVNp25ZVKeegda05sa1mSjBTCQXMdKZ0Kdi2-KhbA0031fwEfd3oPo96gM6Az1H18jm6QcW1DMrJ_yfeLeVT-CObhhDekiJwuRWI4fcIKcvBJQN9rzyEMUnGeE1aShpR0IsP6CqM0Rd7haqEqCoqWKG-bKjyYSlFsO_LUCLfwpO74RX8fNfAO_wvLf4K3c2XaQ</recordid><startdate>20190531</startdate><enddate>20190531</enddate><creator>Mohos, Violetta</creator><creator>Pánovics, Attila</creator><creator>Fliszár-Nyúl, Eszter</creator><creator>Schilli, Gabriella</creator><creator>Hetényi, Csaba</creator><creator>Mladěnka, Přemysl</creator><creator>Needs, Paul W</creator><creator>Kroon, Paul A</creator><creator>Pethő, Gábor</creator><creator>Poór, Miklós</creator><general>MDPI AG</general><general>MDPI</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>MBDVC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-8013-971X</orcidid><orcidid>https://orcid.org/0000-0002-6076-6900</orcidid><orcidid>https://orcid.org/0000-0002-9805-6947</orcidid></search><sort><creationdate>20190531</creationdate><title>Inhibitory Effects of Quercetin and Its Human and Microbial Metabolites on Xanthine Oxidase Enzyme</title><author>Mohos, Violetta ; 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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
= 0.2-0.7 μM); however, pyrogallol inhibited xanthine oxidation (IC
= 1.8 μM) with higher potency vs. 6-MP oxidation (IC
= 10.1 μM). Sulfate and methyl conjugates were approximately ten-fold stronger inhibitors (IC
= 0.2-0.6 μM) of 6-mercaptopurine oxidation than allopurinol (IC
= 7.0 μM), and induced more potent inhibition compared to quercetin (IC
= 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).</abstract><cop>Switzerland</cop><pub>MDPI AG</pub><pmid>31159151</pmid><doi>10.3390/ijms20112681</doi><orcidid>https://orcid.org/0000-0002-8013-971X</orcidid><orcidid>https://orcid.org/0000-0002-6076-6900</orcidid><orcidid>https://orcid.org/0000-0002-9805-6947</orcidid><oa>free_for_read</oa></addata></record> |
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| ispartof | International journal of molecular sciences, 2019-05, Vol.20 (11), p.2681 |
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| source | MDPI - Multidisciplinary Digital Publishing Institute; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central |
| subjects | 6-Mercaptopurine Allopurinol Azathioprine Chromatography Conjugates Dietary supplements Enzymes Flavonoids Granulocytes Inhibitors Metabolites Microflora Microorganisms Oxidation Pharmacology Pharmacy Quercetin Research parks Sulfates Uric acid Xanthine oxidase |
| title | Inhibitory Effects of Quercetin and Its Human and Microbial Metabolites on Xanthine Oxidase Enzyme |
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