Cytochrome P450 reaction phenotyping and inhibition and induction studies of pinostrobin in human liver microsomes and hepatocytes

Publication type:
Journal article
Metadata:
Autoren
  • Shengnan Tan
  • Zhimin Dong
  • Jiashuo Zhang
  • Thomas Efferth
  • Yujie Fu
  • Xin Hua
Autoren-URL
https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:000400604700004&DestLinkType=FullRecord&DestApp=WOS_CPL
DOI
10.1002/bmc.3888
eISSN
1099-0801
Externe Identifier
  • Clarivate Analytics Document Solution ID: ET9CX
  • PubMed Identifier: 28111763
ISSN
0269-3879
Ausgabe der Veröffentlichung
6
Zeitschrift
BIOMEDICAL CHROMATOGRAPHY
Schlüsselwörter
  • CYP induction
  • CYP inhibition
  • hydoxylated metabolite
  • in vitro metabolism
  • pinostrobin
Artikelnummer
ARTN e3888
Datum der Veröffentlichung
2017
Status
Published
Titel
Cytochrome P450 reaction phenotyping and inhibition and induction studies of pinostrobin in human liver microsomes and hepatocytes
Sub types
  • Article
Ausgabe der Zeitschrift
31

Data source: Web of Science (Lite)

Other metadata sources:
Abstract
<jats:title>Abstract</jats:title><jats:p>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 <jats:italic>in vitro</jats:italic>. 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 <jats:italic>in vitro</jats:italic>. In HLMs, PI did not inhibit CYP 1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6 or CYP3A4 (IC<jats:sub>50</jats:sub> &gt; 100 μ<jats:sc>m</jats:sc>). 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.</jats:p>
Autoren
  • Shengnan Tan
  • Zhimin Dong
  • Jiashuo Zhang
  • Thomas Efferth
  • Yujie Fu
  • Xin Hua
DOI
10.1002/bmc.3888
eISSN
1099-0801
ISSN
0269-3879
Ausgabe der Veröffentlichung
6
Zeitschrift
Biomedical Chromatography
Sprache
en
Online publication date
2017
Datum der Veröffentlichung
2017
Status
Published
Herausgeber
Wiley
Herausgeber URL
http://dx.doi.org/10.1002/bmc.3888
Datum der Datenerfassung
2023
Titel
Cytochrome P450 reaction phenotyping and inhibition and induction studies of pinostrobin in human liver microsomes and hepatocytes
Ausgabe der Zeitschrift
31

Data source: Crossref

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 (IC<sub>50</sub>  > 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.
Addresses
  • Key Laboratory of Forest Plant Ecology, Ministry of Education, Northeast Forestry University, 150040, Harbin, PR China.
Autoren
  • Shengnan Tan
  • Zhimin Dong
  • Jiashuo Zhang
  • Thomas Efferth
  • Thomas Efferth
  • Yujie Fu
  • Xin Hua
DOI
10.1002/bmc.3888
eISSN
1099-0801
Externe Identifier
  • PubMed Identifier: 28111763
Funding acknowledgements
  • China Postdoctoral Science Foundation: 2016M591311
Open access
false
ISSN
0269-3879
Ausgabe der Veröffentlichung
6
Zeitschrift
Biomedical chromatography : BMC
Schlüsselwörter
  • Microsomes, Liver
  • Humans
  • Flavanones
  • Cytochrome P-450 Enzyme System
  • Chromatography, Liquid
  • Enzyme Induction
  • Tandem Mass Spectrometry
Sprache
eng
Medium
Print-Electronic
Online publication date
2017
Datum der Veröffentlichung
2017
Status
Published
Datum der Datenerfassung
2017
Titel
Cytochrome P450 reaction phenotyping and inhibition and induction studies of pinostrobin in human liver microsomes and hepatocytes.
Sub types
  • Journal Article
Ausgabe der Zeitschrift
31

Data source: Europe PubMed Central

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.
Date of acceptance
2016
Autoren
  • Shengnan Tan
  • Zhimin Dong
  • Jiashuo Zhang
  • Thomas Efferth
  • Yujie Fu
  • Xin Hua
Autoren-URL
https://www.ncbi.nlm.nih.gov/pubmed/28111763
DOI
10.1002/bmc.3888
eISSN
1099-0801
Ausgabe der Veröffentlichung
6
Zeitschrift
Biomed Chromatogr
Schlüsselwörter
  • CYP induction
  • CYP inhibition
  • hydoxylated metabolite
  • in vitro metabolism
  • pinostrobin
  • Chromatography, Liquid
  • Cytochrome P-450 Enzyme System
  • Enzyme Induction
  • Flavanones
  • Humans
  • Microsomes, Liver
  • Tandem Mass Spectrometry
Sprache
eng
Country
England
Datum der Veröffentlichung
2017
Status
Published
Datum, an dem der Datensatz öffentlich gemacht wurde
2017
Titel
Cytochrome P450 reaction phenotyping and inhibition and induction studies of pinostrobin in human liver microsomes and hepatocytes.
Sub types
  • Journal Article
Ausgabe der Zeitschrift
31

Data source: PubMed

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