Inhibitory effects of quercetin and its human and microbial metabolites on xanthine oxidase enzyme

Violetta Mohos, Attila Pánovics, Eszter Fliszár-Nyúl, Gabriella Schilli, Csaba Hetényi, Přemysl Mladěnka, Paul W. Needs, Paul A. Kroon, Gábor Pethő, Miklós Poór

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3 Citations (Scopus)

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-30-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).

Original languageEnglish
Article number2681
JournalInternational journal of molecular sciences
Volume20
Issue number11
DOIs
Publication statusPublished - Jun 1 2019

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Keywords

  • 6-mercaptopurine
  • Enzyme inhibition
  • Pharmacokinetic interactions
  • Quercetin metabolites
  • Xanthine
  • Xanthine oxidase

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

Cite this

Mohos, V., Pánovics, A., Fliszár-Nyúl, E., Schilli, G., Hetényi, C., Mladěnka, P., Needs, P. W., Kroon, P. A., Pethő, G., & Poór, M. (2019). Inhibitory effects of quercetin and its human and microbial metabolites on xanthine oxidase enzyme. International journal of molecular sciences, 20(11), [2681]. https://doi.org/10.3390/ijms20112681