Abstract
The female flowers of hops are used throughout the world as a flavoring agent for beer. Recently, there has been increasing interest in the potential estrogenic properties of hop extracts. Among the possible estrogenic compounds in hops, 8-prenylnaringenin is perhaps most significant due to its high in vitro potency exceeding that of other known phytoestrogens. Since data regarding the pharmacokinetic properties of this compound are lacking, we investigated the in vitro metabolism of 8-prenylnaringenin by human liver microsomes. A total of 12 metabolites were identified, and biotransformation occurred on the prenyl group and the flavanone skeleton. The major site of oxidation was on the terminal methyl groups, and of the two possible isomers, thetransisomer was more abundant. The double bond on the prenyl group was also oxidized to an epoxide that was opened by intramolecular reaction with the neighboring hydroxyl group. On the flavanone skeleton, the major site of oxidation was at 3′position on the B ring. Other metabolites included oxidation at carbon-3 as well as desaturation of the C ring to produce 8-prenylapigenin. An unusual hydroxy quinone product formed byipsohydroxylation of the B ring of 8-prenylnaringenin was also detected. This product was probably an intermediate for the B ring cleavage product, 8-prenylchromone.
Footnotes
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↵1 Abbreviations used are: 8-PN, 8-prenylnaringenin; HPLC, high-performance liquid chromatography; LC-MS, liquid chromatography-mass spectrometry; M5, 5,4′-dihydroxy-2″,2″-dimethylpyrano-[7,8:6″,5″]flavanone; M7, 5,7,4′-trihydroxy- 8-(2-hydroxy-3-methylbut-3-enyl)flavanone; M10, 5,4′-dihydroxy-[2″-(1-hydroxy- 1-methylethyl)dihydrofurano]-[5″,4″:7,8]flavanone; M2, 5,7-dihydroxy-8-[(E)-4-hydroxy-3-methyl-2-butenyl]-2-(4-hydroxyphenyl)-2,3-dihydro-4H-chromen-4-one; DMSO, dimethyl sulfoxide; M4, (E)-4-[5,7-dihydroxy-2-(4-hydroxyphenyl)-4-oxo- 3,4-dihydro-2H-chromen-8-yl]-2-methyl-2-butenal; CID, collision-induced dissociation; RDA, retro Diels-Alder; 8-PN alcohol, 8-(4″-hydroxyisopentenyl)naringenin; M6, 8-prenylapigenin; M12, 8-prenylchromone.
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Supported by Grant P50AT00155 provided to the University of Illinois at Chicago/National Institutes of Health Center for Botanical Dietary Supplements Research by the Office of Dietary Supplements, the National Institute of General Medical Sciences, the Office for Research on Women's Health, and the National Center for Complementary and Alternative Medicine. Its contents are the responsibility of the authors and do not necessarily represent the official views of the sponsors.
- Received August 20, 2003.
- Accepted October 30, 2003.
- The American Society for Pharmacology and Experimental Therapeutics
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