1. Inhibition of human P450 enzymes by multiple constituents of the Ginkgo biloba extract.
- Author
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Gaudineau C, Beckerman R, Welbourn S, and Auclair K
- Subjects
- Chemical Fractionation, Enzyme Inhibitors chemistry, Ginkgo biloba, Humans, Isoenzymes antagonists & inhibitors, Kinetics, NADP metabolism, Plant Extracts chemistry, Cytochrome P-450 Enzyme Inhibitors, Enzyme Inhibitors pharmacology, Flavonoids pharmacology, Plant Extracts pharmacology, Terpenes pharmacology
- 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).
- Published
- 2004
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