Inhibition of xanthine oxidase-catalyzed xanthine and 6-mercaptopurine oxidation by luteolin, naringenin, myricetin, ampelopsin and their conjugated metabolites

0577377 - MBÚ 2024 RIV NL eng J - Článek v odborném periodiku
Balazs, O. - Dombi, A. - Zsido, B. Z. - Hetenyi, C. - Valentová, Kateřina - Vida, R. G. - Poor, M.
Inhibition of xanthine oxidase-catalyzed xanthine and 6-mercaptopurine oxidation by luteolin, naringenin, myricetin, ampelopsin and their conjugated metabolites.
Biomedicine & Pharmacotherapy. Roč. 167, NOV 2023 (2023), č. článku 115548. ISSN 0753-3322. E-ISSN 1950-6007
Grant CEP: GA ČR(CZ) GA23-04654S
Institucionální podpora: RVO:61388971
Klíčová slova: Xanthine oxidase * Luteolin * Naringenin * Myricetin * Ampelopsin * Flavonoid conjugates
Obor OECD: Pharmacology and pharmacy
Impakt faktor: 7.5, rok: 2022
Způsob publikování: Open access
https://www.sciencedirect.com/science/article/pii/S075333222301346X?via%3Dihub

Luteolin, naringenin, myricetin, and ampelopsin are abundant flavonoids in nature, and several dietary sup-plements also contain them at very high doses. After the peroral intake, flavonoids go through extensive presystemic biotransformation, therefore, typically their sulfate/glucuronic acid conjugates reach high concentrations in the circulation. Xanthine oxidase (XO) enzyme is involved in uric acid production, and it also takes part in the elimination of certain drugs (e.g., 6-mercaptopurine). The inhibitory effects of flavonoid aglycones on XO have been widely studied, however, only limited data are available regarding their sulfate and glucuronic acid conjugates. In this study, we examined the impacts of luteolin, naringenin, myricetin, ampe-lopsin, and their sulfate/glucuronide derivatives on XO-catalyzed xanthine and 6-mercaptopurine oxidations employing in vitro enzyme incubation assays and molecular modeling studies. Our major results/conclusions are the following: (1) Sulfate metabolites were stronger while glucuronic acid derivatives were weaker inhibitors of XO compared to the parent flavonoids. (2) Naringenin, ampelopsin, and their metabolites were weak inhibitors of the enzyme. (3) Luteolin, myricetin, and their sulfates were highly potent inhibitors of XO, and the glucu-ronides of luteolin showed moderate inhibitory impacts. (4) Conjugated metabolites of luteolin and myricetin can be involved in the inhibitory effects of these flavonoids on XO enzyme.
Trvalý link: https://hdl.handle.net/11104/0347153