Inhibition of human P450 enzymes by multiple constituents of the Ginkgo biloba extract

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 (K-i = 14 +/- 4 mug/mL), and to a lesser extent, CYP1A2 (K-i = 106 +/- 24 mug/mL), CYP2E1 (K-i = 127 +/- 42 mug/mL), and CYP3A4 (K-i = 155 +/- 43 mug/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 (K-i = 15 +/- 6 mug/mL) whereas the flavonoidic fraction of EGb761 showed high inhibition of CYP2C9, CYP1A2, CYP2E1, and CYP3A4 (K-i's between 4.9 and 55 mug/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 mug/mL). (C) 2004 Elsevier Inc. All rights reserved.