Effects of catechins, resveratrol, silymarin components, and some of their conjugates on xanthine oxidase-catalyzed xanthine and 6-mercaptopurine oxidation

Bencsik, Tímea and Balázs, Orsolya and Vida, Róbert György and Zsidó, Balázs Zoltán and Hetényi, Csaba and Valentová, Kateřina and Poór, Miklós (2024) Effects of catechins, resveratrol, silymarin components, and some of their conjugates on xanthine oxidase-catalyzed xanthine and 6-mercaptopurine oxidation. JOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE, 105 (5). pp. 2765-2776. ISSN 0022-5142

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Abstract

BACKGROUND: Over the past two decades, the global incidence of gout has markedly increased, affecting people worldwide. Considering the side effects of xanthine oxidase (XO) inhibitor drugs (e.g. allopurinol and febuxostat) used in the treatment of hyperuricemia and gout, the potential application of phytochemicals has been widely studied. In addition, XO also takes part in the elimination of certain drugs, including 6-mercaptopurine. In the current explorative study, we aimed to examine the potential effects of tea catechins, resveratrol, silymarin flavonolignans and some of their conjugated metabolites on XOcatalyzed xanthine and 6-mercaptopurine oxidation, applying in vitro assays and modeling studies. RESULTS: Catechins, resveratrol and resveratrol conjugates exerted no or only weak inhibitory effects on XO. Silybin A, silybin B and isosilybin A were weak, silychristin was a moderate, while 2,3-dehydrosilychristin was a potent inhibitor of the enzyme. Sulfate metabolites of silybin A, silybin B and isosilybin A were considerably stronger inhibitors compared to the parent flavonolignans, and the sulfation of 2,3-dehydrosilychristin slightly increased its inhibitory potency. Silychristin was the sole flavonolignan tested, where sulfate conjugation decreased its inhibitory effect. CONCLUSION: 2,3-Dehydrosilychristin seems to be a promising candidate for examining its in vivo antihyperuricemic effects, because both the parent compound and its sulfate conjugate are highly potent inhibitors of XO. © 2024 The Author(s). Journal of the Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

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