Effects of individual ginsenosides, ginkgolides and flavonoids on CYP2C19 and CYP2D6 activity in human liver microsomes

Clin Exp Pharmacol Physiol. 2006 Sep;33(9):813-5. doi: 10.1111/j.1440-1681.2006.04445.x.

Abstract

1. The effects of four individual ginsenosides (Rb1, Rb2, Rc and Rd), two ginkgolides (A and B) and one flavonoid (quercetin) on CYP2C19-dependent S-mephenytoin 4 cent-hydroxylation and CYP2D6-mediated bufuralol 1 cent-hydroxylation were evaluated in human liver microsomes. 2. Increasing concentrations of each test compound were added to microsomal incubation mixtures containing a well-characterized marker substrate (S-mephenytoin for CYP2C19 or bufuralol for CYP2D6) to determine their IC(50) values (compound concentration yielding 50% inhibition of a marker enzyme activity), which were estimated by graphical inspection. 3. For CYP2C19, the IC(50) values were 46, 46 and 62 micromol/L for ginsenoside Rd, quercetin and ginsenoside Rb2, respectively, whereas only ginsenoside Rd had an IC(50) value of 57 micromol/L for CYP2D6. 4. The data suggest that the tested compounds are not likely to inhibit the metabolism of the concurrent use of a given drug whose primary route of elimination is through CYP2C19 or CYP2D6.

Publication types

  • Comparative Study
  • Evaluation Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Aryl Hydrocarbon Hydroxylases / metabolism*
  • Cytochrome P-450 CYP2C19
  • Cytochrome P-450 CYP2C9
  • Cytochrome P-450 CYP2D6 / metabolism*
  • Cytochrome P-450 CYP3A
  • Cytochrome P-450 Enzyme System / metabolism
  • Dose-Response Relationship, Drug
  • Ethanolamines / analysis
  • Flavonoids / pharmacology*
  • Ginkgo biloba / chemistry
  • Ginkgolides / pharmacology*
  • Ginsenosides / pharmacology*
  • Humans
  • Inhibitory Concentration 50
  • Mephenytoin / metabolism
  • Microsomes, Liver / drug effects*
  • Mixed Function Oxygenases / metabolism*

Substances

  • Ethanolamines
  • Flavonoids
  • Ginkgolides
  • Ginsenosides
  • Ro 03-7410
  • Cytochrome P-450 Enzyme System
  • Mixed Function Oxygenases
  • CYP2C9 protein, human
  • Cytochrome P-450 CYP2C9
  • Aryl Hydrocarbon Hydroxylases
  • CYP2C19 protein, human
  • Cytochrome P-450 CYP2C19
  • Cytochrome P-450 CYP2D6
  • Cytochrome P-450 CYP3A
  • CYP3A4 protein, human
  • Mephenytoin