title: Cytochrome P450 reaction phenotyping and inhibition and induction studies of pinostrobin in human liver microsomes and hepatocytes.
abstract: Pinostrobin (PI, 5-hydroxy-7-methoxyflavanone) is a natural flavonoid known for its rich pharmacological activities. The objective of this study was to identify the human liver cytochrome P450 (CYP450) isoenzymes involved in the metabolism of PI. A single hydoxylated metabolite was obtained from PI after an incubation with pooled human liver microsomes (HLMs). The relative contributions of different CYP450s were evaluated using CYP450-selective inhibitors in HLMs and recombinant human CYP450 enzymes, and the results revealed the major involvement of CYP1A2, CYP2C9 and CYP2E1 in PI metabolism. We also evaluated the ability of PI to inhibit and induce human cytochrome P450 enzymes in vitro. High-performance liquid chromatography and liquid chromatography-tandem mass spectrometry analytical techniques were used to estimate the enzymatic activities of seven drug-metabolizing CYP450 isozymes in vitro. In HLMs, PI did not inhibit CYP 1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6 or CYP3A4 (IC50> 100 μm). In the induction studies, PI had minimal effects on CYP1A2, CYP2B6and CYP3A4 activity. Based on these results, PI would not be expected to cause clinically significant CYP450 inhibition or induction.
authors.affiliation: Key Laboratory of Forest Plant Ecology, Ministry of Education, Northeast Forestry University, 150040, Harbin, PR China.|Engineering Research Center of Forest Bio-preparation, Ministry of Education, Northeast Forestry University, 150040, Harbin, PR China.|Key Laboratory of Saline-alkali Vegetation Ecology Restoration in Oil Field, Ministry of Education, Northeast Forestry University, Harbin, PR China.
authors.forename: Shengnan
authors.initials: S
authors.lastname: Tan
authors.affiliation: Tianjin Animal Science and Veterinary Research Institute, Tianjin, PR China.|Veteria Veterinary Research Institute, Tianjin, PR China.
authors.forename: Zhimin
authors.initials: Z
authors.lastname: Dong
authors.affiliation: College of Life Science, Northeast Forestry University, Harbin, PR China.
authors.forename: Jiashuo
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Pharmaceutical Biology, Institute of Pharmacy, University of Mainz, Mainz, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Efferth
authors.affiliation: Key Laboratory of Forest Plant Ecology, Ministry of Education, Northeast Forestry University, 150040, Harbin, PR China.|Engineering Research Center of Forest Bio-preparation, Ministry of Education, Northeast Forestry University, 150040, Harbin, PR China.
authors.forename: Yujie
authors.initials: Y
authors.lastname: Fu
authors.affiliation: Division of Bacterial Diseases, State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute,Chinese Academy of Agricultural Sciences, Harbin, PR China.
authors.forename: Xin
authors.initials: X
authors.lastname: Hua
mesh_terms: D002853:Chromatography, Liquid; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis / Q000378:metabolism*; D004790:Enzyme Induction; D044950:Flavanones / Q000494:pharmacology*; D006801:Humans; D008862:Microsomes, Liver / Q000187:drug effects* / Q000201:enzymology; D053719:Tandem Mass Spectrometry
chemical_list: D044950:Flavanones; D003577:Cytochrome P-450 Enzyme System; C411294:pinostrobin
keywords: CYP induction; CYP inhibition; hydoxylated metabolite; in vitro metabolism; pinostrobin