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The Effect of Flavonoid Aglycones on the CYP1A2, CYP2A6, CYP2C8 and CYP2D6 Enzymes Activity
- Source :
- Molecules, Volume 24, Issue 17, Molecules, Vol 24, Iss 17, p 3174 (2019)
- Publication Year :
- 2019
- Publisher :
- Multidisciplinary Digital Publishing Institute, 2019.
-
Abstract
- Cytochromes P450 are major metabolic enzymes involved in the biotransformation of xenobiotics. The majority of xenobiotics are metabolized in the liver, in which the highest levels of cytochromes P450 are expressed. Flavonoids are natural compounds to which humans are exposed through everyday diet. In the previous study, selected flavonoid aglycones showed inhibition of CYP3A4 enzyme. Thus, the objective of this study was to determine if these flavonoids inhibit metabolic activity of CYP1A2, CYP2A6, CYP2C8, and CYP2D6 enzymes. For this purpose, the O-deethylation reaction of phenacetin was used for monitoring CYP1A2 enzyme activity, coumarin 7-hydroxylation for CYP2A6 enzyme activity, 6-α-hydroxylation of paclitaxel for CYP2C8 enzyme activity, and dextromethorphan O-demethylation for CYP2D6 enzyme activity. The generated metabolites were monitored by high-performance liquid chromatography coupled with diode array detection. Hesperetin, pinocembrin, chrysin, isorhamnetin, and morin inhibited CYP1A2 activity<br />apigenin, tangeretin, galangin, and isorhamnetin inhibited CYP2A6 activity<br />and chrysin, chrysin-dimethylether, and galangin inhibited CYP2C8. None of the analyzed flavonoids showed inhibition of CYP2D6. The flavonoids in this study were mainly reversible inhibitors of CYP1A2 and CYP2A6, while the inhibition of CYP2C8 was of mixed type (reversible and irreversible). The most prominent reversible inhibitor of CYP1A2 was chrysin, and this was confirmed by the docking study.
- Subjects :
- CYP2A6
CYP2C8
CYP1A2
Pharmaceutical Science
030226 pharmacology & pharmacy
Article
Analytical Chemistry
Substrate Specificity
lcsh:QD241-441
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
lcsh:Organic chemistry
Cytochrome P-450 Enzyme System
Drug Discovery
Humans
Chrysin
Physical and Theoretical Chemistry
Isorhamnetin
Pinocembrin
biology
CYP2D6
Organic Chemistry
Hesperetin
flavonoids
inhibition
Enzyme assay
3. Good health
Galangin
Molecular Docking Simulation
chemistry
Biochemistry
Chemistry (miscellaneous)
030220 oncology & carcinogenesis
Apigenin
biology.protein
Molecular Medicine
Subjects
Details
- Language :
- English
- ISSN :
- 14203049
- Database :
- OpenAIRE
- Journal :
- Molecules
- Accession number :
- edsair.doi.dedup.....58eab23d70cb7494d149f56ab24175a7
- Full Text :
- https://doi.org/10.3390/molecules24173174