Effects of individual ginsenosides, ginkgolides and flavonoids on CYP2C19 and CYP2D6 activity in human liver microsomes.
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.
He
Nu
N
Department of Pharmacology and Toxicology, Morehouse School of Medicine, Atlanta, Georgia 30310-1458, USA. nhe@msm.edu
Xie
Hong-Guang
HG
Collins
Xavier
X
Edeki
Timi
T
Yan
Zhengyin
Z
D001189:Aryl Hydrocarbon Hydroxylases / Q000378:metabolism*; D065731:Cytochrome P-450 CYP2C19; D065729:Cytochrome P-450 CYP2C9; D019389:Cytochrome P-450 CYP2D6 / Q000378:metabolism*; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004983:Ethanolamines / Q000032:analysis; D005419:Flavonoids / Q000494:pharmacology*; D020441:Ginkgo biloba / Q000737:chemistry; D046934:Ginkgolides / Q000494:pharmacology*; D036145:Ginsenosides / Q000494:pharmacology*; D006801:Humans; D020128:Inhibitory Concentration 50; D008617:Mephenytoin / Q000378:metabolism; D008862:Microsomes, Liver / Q000187:drug effects*; D006899:Mixed Function Oxygenases / Q000378:metabolism*
D004983:Ethanolamines; D005419:Flavonoids; D046934:Ginkgolides; D036145:Ginsenosides; C039685:Ro 03-7410; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D019389:Cytochrome P-450 CYP2D6; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; D008617:Mephenytoin