Interactions of resveratrol and its metabolites (resveratrol-3-sulfate, resveratrol-3-glucuronide, and dihydroresveratrol) with serum albumin, cytochrome P450 enzymes, and OATP transporters

Miklós Poór; Hana Kaci; Slávka Bodnárová; Violetta Mohos; Eszter Fliszár-Nyúl; Sándor Kunsági-Máté; Csilla Özvegy-Laczka; Beáta Lemli

Biomedicine & Pharmacotherapy (Jul 2022)

Interactions of resveratrol and its metabolites (resveratrol-3-sulfate, resveratrol-3-glucuronide, and dihydroresveratrol) with serum albumin, cytochrome P450 enzymes, and OATP transporters

Miklós Poór,
Hana Kaci,
Slávka Bodnárová,
Violetta Mohos,
Eszter Fliszár-Nyúl,
Sándor Kunsági-Máté,
Csilla Özvegy-Laczka,
Beáta Lemli

Affiliations

Miklós Poór: Department of Pharmacology, Faculty of Pharmacy, University of Pécs, Rókus u. 2, Pécs H-7624, Hungary; Food Biotechnology Research Group, János Szentágothai Research Centre, University of Pécs, Ifjúság útja 20, Pécs H-7624, Hungary; Corresponding author at: Department of Pharmacology, Faculty of Pharmacy, University of Pécs, Rókus u. 2, Pécs H-7624, Hungary.
Hana Kaci: Drug Resistance Research Group, Institute of Enzymology, Research Centre for Natural Sciences, Eötvös Loránd Research Network, Magyar tudósok krt. 2., H-1117 Budapest, Hungary; Doctoral School of Biology, Institute of Biology, Eötvös Loránd University, Pázmány P. stny. 1/C, H-1117 Budapest, Hungary
Slávka Bodnárová: Department of Pharmacology, Faculty of Pharmacy, University of Pécs, Rókus u. 2, Pécs H-7624, Hungary; Food Biotechnology Research Group, János Szentágothai Research Centre, University of Pécs, Ifjúság útja 20, Pécs H-7624, Hungary
Violetta Mohos: Department of Pharmacology, Faculty of Pharmacy, University of Pécs, Rókus u. 2, Pécs H-7624, Hungary; Food Biotechnology Research Group, János Szentágothai Research Centre, University of Pécs, Ifjúság útja 20, Pécs H-7624, Hungary
Eszter Fliszár-Nyúl: Department of Pharmacology, Faculty of Pharmacy, University of Pécs, Rókus u. 2, Pécs H-7624, Hungary; Food Biotechnology Research Group, János Szentágothai Research Centre, University of Pécs, Ifjúság útja 20, Pécs H-7624, Hungary
Sándor Kunsági-Máté: Department of Organic and Medicinal Chemistry, Faculty of Pharmacy, University of Pécs, Szigeti út 12, Pécs H-7624, Hungary; Green Chemistry Research Group, János Szentágothai Research Centre, University of Pécs, Ifjúság útja 20, Pécs H-7624, Hungary
Csilla Özvegy-Laczka: Drug Resistance Research Group, Institute of Enzymology, Research Centre for Natural Sciences, Eötvös Loránd Research Network, Magyar tudósok krt. 2., H-1117 Budapest, Hungary
Beáta Lemli: Department of Pharmacology, Faculty of Pharmacy, University of Pécs, Rókus u. 2, Pécs H-7624, Hungary; Department of Organic and Medicinal Chemistry, Faculty of Pharmacy, University of Pécs, Szigeti út 12, Pécs H-7624, Hungary; Green Chemistry Research Group, János Szentágothai Research Centre, University of Pécs, Ifjúság útja 20, Pécs H-7624, Hungary

Journal volume & issue: Vol. 151
p. 113136

Abstract

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Resveratrol (RES) is a widely-known natural polyphenol which is also contained by several dietary supplements. Large doses of RES can result in high micromolar levels of its sulfate and glucuronide conjugates in the circulation, due to the high presystemic metabolism of the parent polyphenol. Pharmacokinetic interactions of RES have been extensively studied, while only limited data are available regarding its metabolites. Therefore, in the current study, we examined the interactions of resveratrol-3-sulfate (R3S), resveratrol-3-glucuronide, and dihydroresveratrol (DHR; a metabolite produced by the colon microbiota) with human serum albumin (HSA), cytochrome P450 (CYP) enzymes, and organic anion transporting polypeptides (OATP) employing in vitro models. Our results demonstrated that R3S and R3G may play a major role in the RES-induced pharmacokinetic interactions: (1) R3S can strongly displace the site I marker warfarin from HSA; (2) R3G showed similarly strong inhibitory action on CYP3A4 to RES; (3) R3S proved to be similarly strong (OATP1B1/3) or even stronger (OATP1A2 and OATP2B1) inhibitor of OATPs tested than RES, while R3G and RES showed comparable inhibitory actions on OATP2B1.

Published in Biomedicine & Pharmacotherapy

ISSN: 0753-3322 (Print); 1950-6007 (Online)
Publisher: Elsevier
Country of publisher: France
LCC subjects: Medicine: Therapeutics. Pharmacology
Website: https://www.journals.elsevier.com/biomedicine-and-pharmacotherapy

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