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Effects of chrysin and its major conjugated metabolites chrysin-7-sulfate and chrysin-7-glucuronide on cytochrome P450 enzymes, and on OATP, P-gp, BCRP and MRP2 transporters

Mohos, Violetta and Fliszár-Nyúl, Eszter and Ungvári, Orsolya and Bakos, Éva and Kuffa, Katalin and Bencsik, Tímea and Zsidó, Balázs Zoltán and Hetényi, Csaba and Telbisz, Ágnes and Özvegy-Laczka, Csilla and Poór, Miklós (2020) Effects of chrysin and its major conjugated metabolites chrysin-7-sulfate and chrysin-7-glucuronide on cytochrome P450 enzymes, and on OATP, P-gp, BCRP and MRP2 transporters. DRUG METABOLISM AND DISPOSITION, 48 (9). pp. 1-45. ISSN 0090-9556 (print); 1521-009X (online)

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Abstract

Chrysin is an abundant flavonoid in nature, and it is also contained by several dietary supplements. Chrysin is highly biotransformed in the body, during which conjugated metabolites, chrysin-7-sulfate and chrysin-7-glucuronide are formed. These conjugates appear at considerably higher concentrations in the circulation than the parent compound. Based on previous studies, chrysin can interact with biotransformation enzymes and transporters; however, the interactions of its metabolites have been barely examined. In this in vitro study, the effects of chrysin, chrysin-7-sulfate, and chrysin-7-glucuronide on CYP (2C9, 2C19, 3A4, and 2D6) as well as on Organic anion-transporting polypeptides (OATPs, 1A2, 1B1, 1B3, and 2B1) and ATP Binding Cassette (ABC: P-gp, MRP2, and BCRP) transporters were investigated. Our observations revealed that chrysin conjugates are strong inhibitors of certain biotransformation enzymes (e.g., CYP2C9) and transporters (e.g., OATP1B1, OATP1B3, OATP2B1, and BCRP) examined. Therefore, the simultaneous administration of chrysin-containing dietary supplements with medications needs to be carefully considered due to the possible development of pharmacokinetic interactions. Significance Statement Chrysin-7-sulfate and chrysin-7-glucuronide are the major metabolites of flavonoid chrysin. In this study, we examined the effects of chrysin and its conjugates on cytochrome P450 enzymes, and on Organic anion-transporting polypeptides and ATP Binding Cassette transporters (P-gp, BCRP, and MRP2). Our results demonstrate that chrysin and/or its conjugates can significantly inhibit some of these proteins. Since chrysin is also contained by dietary supplements, high intake of chrysin may interrupt the transport and/or the biotransformation of drugs.

Item Type: Article
Uncontrolled Keywords: Flavonoids; Pharmacokinetic; cytochrome P450 (CYP); ABC efflux transporters; Uptake transporters (OATP, OAT, OCT, PEPT, MCT, NTCP, ASBT, etc.)
Subjects: Q Science / természettudomány > QH Natural history / természetrajz > QH301 Biology / biológia > QH3011 Biochemistry / biokémia
SWORD Depositor: MTMT SWORD
Depositing User: MTMT SWORD
Date Deposited: 15 Sep 2020 14:33
Last Modified: 15 Sep 2020 14:33
URI: http://real.mtak.hu/id/eprint/113355

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