title: Inhibition of human P450 enzymes by multiple constituents of the Ginkgo biloba extract.
abstract: The Ginkgo biloba extract EGb761 was tested for its ability to inhibit the major human cytochrome P450 enzymes (CYPs). The full extract was found to strongly inhibit CYP2C9 (Ki = 14+/- 4 microg/mL), and to a lesser extent, CYP1A2 (Ki = 106 +/- 24 microg/mL), CYP2E1 (Ki = 127 +/- 42 microg/mL), and CYP3A4 (Ki = 155 +/- 43 microg/mL). The terpenoidic and flavonoidic fractions of the extract were tested separately against the same P450s to identify the source of inhibition by EGb761. The terpenoidic fraction inhibited only CYP2C9 (Ki = 15 +/-6 microg/mL) whereas the flavonoidic fraction of EGb761 showed high inhibition of CYP2C9, CYP1A2, CYP2E1, and CYP3A4 (Ki's between 4.9 and 55 microg/mL). The flavonoidic fraction was further fractionated using extraction and chromatography. Inhibition studies indicated that the majority of these fractions inhibited P450s at a significant level (IC50 < 40 microg/mL).
authors.affiliation: Department of Chemistry, McGill University, 801 Sherbrooke Street West, Montréal, Que., Canada H3A 2K6.
authors.forename: Cédric
authors.initials: C
authors.lastname: Gaudineau
authors.forename: Rachel
authors.initials: R
authors.lastname: Beckerman
authors.forename: Sarah
authors.initials: S
authors.lastname: Welbourn
authors.forename: Karine
authors.initials: K
authors.lastname: Auclair
mesh_terms: D005591:Chemical Fractionation; D065607:Cytochrome P-450 Enzyme Inhibitors; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D005419:Flavonoids / Q000494:pharmacology*; D020441:Ginkgo biloba; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors; D007700:Kinetics; D009249:NADP / Q000378:metabolism; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D013729:Terpenes / Q000494:pharmacology*; D000096983:Ginkgo Extract
chemical_list: D065607:Cytochrome P-450 Enzyme Inhibitors; D004791:Enzyme Inhibitors; D005419:Flavonoids; D007527:Isoenzymes; D009249:NADP; D010936:Plant Extracts; D013729:Terpenes; C063170:Ginkgo biloba extract; D000096983:Ginkgo Extract