title: Investigation of selective inhibitory effects of glycyrol on human CYP 1A1 and 2C9.
abstract: 1. Glycyrol is a coumarin derivative isolated from the roots of Glycyrrhiza uralensis called Gamcho in Korea and commonly used as a sweetener in oriental medicine. Glycyrol shows several biological activities, including anti-oxidative, anti-inflammatory, antibacterial, anti-angiogenic, and anti-allergenic properties. Although there have been studies on the biological effects of glycyrol, the inhibitory effects of glycyrol on cytochrome P450 (CYP) activities have not been investigated. 2. We investigated the inhibitory effects of glycyrol on the activities of CYP isoforms using a cocktail of probe substrates in pooled human liver microsome (HLM) and human recombinant cDNA-expressed CYPs. Glycyrol strongly inhibited CYP1A-mediated phenacetin O-deethylation and CYP2C9-mediated diclofenac 4'-hydroxylation in HLMs, which were the result of competitive inhibition as revealed by a Dixon plot. In addition, glycyrol showed selective inhibition of CYP1A1- and CYP1A2-catalyzed phenacetin O-deethylase activity with a half-maximal inhibitory concentration of (IC50) 1.3 and 16.1 μM in human recombinant cDNA-expressed CYP1A1 and CYP1A2, respectively. 3. Glycyrol decreased CYP2C9-catalyzed diclofenac 4'-hydroxylation activity with IC50 values of 0.67 μM in human recombinant cDNA-expressed CYP2C9. This is the first investigation of competitive inhibitory effects on CYP1A1 and CYP2C9 in HLMs.
authors.affiliation: a College of Pharmacy, Research Institute of Pharmaceutical Sciences, Kyungpook National University , Daegu , Republic of Korea and.
authors.forename: Sun Joo
authors.initials: SJ
authors.lastname: Kim
authors.affiliation: a College of Pharmacy, Research Institute of Pharmaceutical Sciences, Kyungpook National University , Daegu , Republic of Korea and.
authors.forename: Su Jin
authors.initials: SJ
authors.lastname: Kim
authors.affiliation: b College of Agriculture and Life Sciences, Kyungpook National University , Daegu , Republic of Korea.
authors.forename: Miri
authors.initials: M
authors.lastname: Hong
authors.affiliation: a College of Pharmacy, Research Institute of Pharmaceutical Sciences, Kyungpook National University , Daegu , Republic of Korea and.
authors.forename: Hyun Gyu
authors.initials: HG
authors.lastname: Choi
authors.affiliation: a College of Pharmacy, Research Institute of Pharmaceutical Sciences, Kyungpook National University , Daegu , Republic of Korea and.
authors.forename: Jeong Ah
authors.initials: JA
authors.lastname: Kim
authors.affiliation: a College of Pharmacy, Research Institute of Pharmaceutical Sciences, Kyungpook National University , Daegu , Republic of Korea and.
authors.forename: Sangkyu
authors.initials: S
authors.lastname: Lee
mesh_terms: D019363:Cytochrome P-450 CYP1A1 / Q000378:metabolism*; D065729:Cytochrome P-450 CYP2C9 / Q000378:metabolism*; D065607:Cytochrome P-450 Enzyme Inhibitors / Q000494:pharmacology*; D005419:Flavonoids / Q000494:pharmacology*; D006801:Humans; D008862:Microsomes, Liver / Q000378:metabolism; D056910:Republic of Korea
chemical_list: D065607:Cytochrome P-450 Enzyme Inhibitors; D005419:Flavonoids; C531349:glycyrol; D065729:Cytochrome P-450 CYP2C9; D019363:Cytochrome P-450 CYP1A1
keywords: Competitive inhibition; cytochrome P450s; glycyrol; glycyrrhiza uralensis; human liver microsomes