PlumX Metrics
Embed PlumX Metrics

In vitro modulatory effects of flavonoids on human cytochrome P450 2C8 (CYP2C8)

Naunyn-Schmiedeberg's Archives of Pharmacology, ISSN: 0028-1298, Vol: 385, Issue: 5, Page: 495-502
2012
  • 20
    Citations
  • 0
    Usage
  • 17
    Captures
  • 0
    Mentions
  • 0
    Social Media
Metric Options:   Counts1 Year3 Year

Metrics Details

Article Description

The inhibitory effects of five flavonoidswith distinct chemical classes (flavones [luteolin], flavonols [quercetin and quercitrin], and flavanones [hesperetin and hespiridin]) on cDNA-expressed CYP2C8 were investigated. CYP2C8 was co-expressed with NADPH-cytochrome P450 reductase in Escherichia coli and used to characterise potency and mechanism of these flavonoids on the isoform. Tolbutamide 4-methylhydroxylase, a high-performance liquid chromatography-based assay, was selected as marker activity for CYP2C8. Our results indicated that the flavonoids inhibited CYP2C8 with different potency. The order of inhibitory activities was quercetin > luteolin > hesperetin > hesperidin > quercitrin. All of these compounds however exhibited mechanism-based inhibition. A number of structural factors were found to be important for inhibition; these include the molecular shape (volume to surface ratio), the number of hydroxyl groups as well as glycosylation of the hydroxyl group. Quercetin was the most potent inhibitor among the flavonoids examined in this study, and our data suggest that it should be examined for potential pharmacokinetic drug interactions pertaining to CYP2C8 substrates in vivo. © 2012 Springer-Verlag.

Provide Feedback

Have ideas for a new metric? Would you like to see something else here?Let us know