2. Academic Validation
  3. Inhibitory Effects of Quercetin and Its Human and Microbial Metabolites on Xanthine Oxidase Enzyme

Inhibitory Effects of Quercetin and Its Human and Microbial Metabolites on Xanthine Oxidase Enzyme

  • Int J Mol Sci. 2019 May 31;20(11):2681. doi: 10.3390/ijms20112681.
Violetta Mohos 1 2,  Attila Pánovics 3,  Eszter Fliszár-Nyúl 4 5,  Gabriella Schilli 6,  Csaba Hetényi 7,  Přemysl Mladěnka 8,  Paul W Needs 9,  Paul A Kroon 10,  Gábor Pethő 11 12,  Miklós Poór 13 14
Affiliations

Affiliations

  • 1 Department of Pharmacology, University of Pécs, Faculty of Pharmacy, Szigeti út 12, H-7624 Pécs, Hungary. mohos.violetta@gytk.pte.hu.
  • 2 János Szentágothai Research Center, University of Pécs, Ifjúság útja 20, H-7624 Pécs, Hungary. mohos.violetta@gytk.pte.hu.
  • 3 Department of Pharmacology, University of Pécs, Faculty of Pharmacy, Szigeti út 12, H-7624 Pécs, Hungary. attilapanovics@gmail.com.
  • 4 Department of Pharmacology, University of Pécs, Faculty of Pharmacy, Szigeti út 12, H-7624 Pécs, Hungary. eszter.nyul@aok.pte.hu.
  • 5 János Szentágothai Research Center, University of Pécs, Ifjúság útja 20, H-7624 Pécs, Hungary. eszter.nyul@aok.pte.hu.
  • 6 Department of Pharmacology and Pharmacotherapy, University of Pécs, Medical School, Szigeti út 12, H-7624 Pécs, Hungary. scgpecs@gmail.com.
  • 7 Department of Pharmacology and Pharmacotherapy, University of Pécs, Medical School, Szigeti út 12, H-7624 Pécs, Hungary. csabahete@yahoo.com.
  • 8 Department of Pharmacology and Toxicology, Faculty of Pharmacy in Hradec Králové, Charles University, Heyrovského 1203, 500 05 Hradec Králové, Czech Republic. mladenkap@faf.cuni.cz.
  • 9 Quadram Institute Bioscience, Norwich Research Park, Norwich NR4 7UA, UK. paul.needs@quadram.ac.uk.
  • 10 Quadram Institute Bioscience, Norwich Research Park, Norwich NR4 7UA, UK. paul.kroon@quadram.ac.uk.
  • 11 Department of Pharmacology, University of Pécs, Faculty of Pharmacy, Szigeti út 12, H-7624 Pécs, Hungary. gabor.petho@aok.pte.hu.
  • 12 Department of Pharmacology and Pharmacotherapy, University of Pécs, Medical School, Szigeti út 12, H-7624 Pécs, Hungary. gabor.petho@aok.pte.hu.
  • 13 Department of Pharmacology, University of Pécs, Faculty of Pharmacy, Szigeti út 12, H-7624 Pécs, Hungary. poor.miklos@pte.hu.
  • 14 János Szentágothai Research Center, University of Pécs, Ifjúság útja 20, H-7624 Pécs, Hungary. poor.miklos@pte.hu.
PMID: 31159151 DOI: 10.3390/ijms20112681
Abstract

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 (IC50 = 0.2-0.7 μM); however, pyrogallol inhibited xanthine oxidation (IC50 = 1.8 μM) with higher potency vs. 6-MP oxidation (IC50 = 10.1 μM). Sulfate and methyl conjugates were approximately ten-fold stronger inhibitors (IC50 = 0.2-0.6 μM) of 6-mercaptopurine oxidation than allopurinol (IC50 = 7.0 μM), and induced more potent inhibition compared to quercetin (IC50 = 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).

Keywords

6-mercaptopurine; enzyme inhibition; pharmacokinetic interactions; quercetin metabolites; xanthine; xanthine oxidase.

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