title: Inhibition of human cytochrome P450 enzymes by hops (Humulus lupulus) and hop prenylphenols.
abstract: As hops (Humulus lupulus L.) are used in the brewing of beer and by menopausal women as estrogenic dietary supplements, the potential for hop extracts and hop constituents to cause drug-botanical interactions by inhibiting human cytochrome P450 enzymes was investigated. Inhibition of major human cytochrome P450 enzymes by a standardized hop extract and isolated hop prenylated phenols was evaluated using a fast and efficient assay based on ultrahigh pressure liquid chromatography-tandem mass spectrometry. The hop extract at 5 μg/mL inhibited CYP2C8 (93%), CYP2C9 (88%), CYP2C19 (70%), and CYP1A2 (27%) with IC50 values of 0.8, 0.9, 3.3, and 9.4 μg/mL, respectively, but time-dependent inactivation was observed only for CYP1A2. Isoxanthohumol from hops was the most potent inhibitor of CYP2C8 with an IC50 of 0.2 μM, whereas 8-prenylnaringenin was the most potent inhibitor of CYP1A2, CYP2C9 and CYP2C19 with IC50 values of 1.1 μM, 1.1 μM and 0.4 μM, respectively. Extracts of hops contain prenylated compounds such as the flavanones isoxanthohumol and 8-prenylnaringenin and the chalcone xanthohumol that can inhibit CYP450s, especially the CYP2C family, which may affect the efficacy and safety of some CYP2C substrate drugs when co-administered.
authors.affiliation: UIC/NIH Center for Botanical Dietary Supplements Research, Department of Medicinal Chemistry and Pharmacognosy, University of Illinois College of Pharmacy, Chicago, Illinois 60612-72312.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yuan
authors.affiliation: UIC/NIH Center for Botanical Dietary Supplements Research, Department of Medicinal Chemistry and Pharmacognosy, University of Illinois College of Pharmacy, Chicago, Illinois 60612-72312.
authors.forename: Xi
authors.initials: X
authors.lastname: Qiu
authors.affiliation: UIC/NIH Center for Botanical Dietary Supplements Research, Department of Medicinal Chemistry and Pharmacognosy, University of Illinois College of Pharmacy, Chicago, Illinois 60612-72312.
authors.forename: Dejan
authors.initials: D
authors.lastname: Nikolić
authors.affiliation: UIC/NIH Center for Botanical Dietary Supplements Research, Department of Medicinal Chemistry and Pharmacognosy, University of Illinois College of Pharmacy, Chicago, Illinois 60612-72312.
authors.forename: Shao-Nong
authors.initials: SN
authors.lastname: Chen
authors.affiliation: UIC/NIH Center for Botanical Dietary Supplements Research, Department of Medicinal Chemistry and Pharmacognosy, University of Illinois College of Pharmacy, Chicago, Illinois 60612-72312.
authors.forename: Ke
authors.initials: K
authors.lastname: Huang
authors.affiliation: UIC/NIH Center for Botanical Dietary Supplements Research, Department of Medicinal Chemistry and Pharmacognosy, University of Illinois College of Pharmacy, Chicago, Illinois 60612-72312.
authors.forename: Guannan
authors.initials: G
authors.lastname: Li
authors.affiliation: UIC/NIH Center for Botanical Dietary Supplements Research, Department of Medicinal Chemistry and Pharmacognosy, University of Illinois College of Pharmacy, Chicago, Illinois 60612-72312.
authors.forename: Guido F
authors.initials: GF
authors.lastname: Pauli
authors.affiliation: UIC/NIH Center for Botanical Dietary Supplements Research, Department of Medicinal Chemistry and Pharmacognosy, University of Illinois College of Pharmacy, Chicago, Illinois 60612-72312.
authors.forename: Richard B
authors.initials: RB
authors.lastname: van Breemen
mesh_terms: D002851:Chromatography, High Pressure Liquid; D065607:Cytochrome P-450 Enzyme Inhibitors; D006801:Humans; D027582:Humulus; D008862:Microsomes, Liver / Q000378:metabolism; D004364:Pharmaceutical Preparations / Q000378:metabolism; D010636:Phenols / Q000494:pharmacology*; D010936:Plant Extracts / Q000494:pharmacology*; D053719:Tandem Mass Spectrometry
chemical_list: D065607:Cytochrome P-450 Enzyme Inhibitors; D004364:Pharmaceutical Preparations; D010636:Phenols; D010936:Plant Extracts
keywords: 8-Prenylnaringenin; Cytochrome P450 inhibition; Drug–botanical interactions; Hops; Isoxanthohumol