RT Journal Article
SR Electronic
T1 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
JF Drug Metabolism and Disposition
JO Drug Metab Dispos
FD American Society for Pharmacology and Experimental Therapeutics
SP DMD-AR-2020-000085
DO 10.1124/dmd.120.000085
A1 Violetta Mohos
A1 Eszter Fliszár-Nyúl
A1 Orsolya Ungvári
A1 Éva Bakos
A1 Katalin Kuffa
A1 Tímea Bencsik
A1 Balázs Zoltán Zsidó
A1 Csaba Hetényi
A1 Ágnes Telbisz
A1 Csilla Özvegy-Laczka
A1 Miklós Poór
YR 2020
UL http://dmd.aspetjournals.org/content/early/2020/07/13/dmd.120.000085.abstract
AB 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.