title: Effects of individual ginsenosides, ginkgolides and flavonoids on CYP2C19 and CYP2D6 activity in human liver microsomes.
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.
authors.affiliation: Department of Pharmacology and Toxicology, Morehouse School of Medicine, Atlanta, Georgia 30310-1458, USA. nhe@msm.edu
authors.forename: Nu
authors.initials: N
authors.lastname: He
authors.forename: Hong-Guang
authors.initials: HG
authors.lastname: Xie
authors.forename: Xavier
authors.initials: X
authors.lastname: Collins
authors.forename: Timi
authors.initials: T
authors.lastname: Edeki
authors.forename: Zhengyin
authors.initials: Z
authors.lastname: Yan
mesh_terms: 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*
chemical_list: 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