Induction of cytochrome P450s by terpene trilactones and flavonoids of the Ginkgo biloba extract EGb 761 in rats.

Full Abstract

1. Ginkgo biloba is one of the most popular herbal medicines worldwide due to its memory-enhancing and cognition-improving effects. The current study was designed to investigate the effects of five major constituents (bilobalide, ginkgolide A, B, quercetin, and kaempferol) in the standardized G. biloba extract EGb 761 on various cytochrome P450s (CYPs) in rats. 2. The activity of CYP450 was measured by the quantification of six metabolites from multiple cytochrome P450 probe substrates using a validated liquid chromatography coupled with tandem mass spectrometry detection (LC-MS/MS) method. The levels of messenger RNA (mRNA) and protein of various CYPs were determined by reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blotting analysis, respectively. 3. Bilobalide significantly induced the activity, protein, and mRNA expression of CYP3A1 and 1A2, and increased CYP2E1 activity and CYP2B1/2 protein expression in a dose-dependent manner. 4. Ginkgolide A, B, quercetin, and kaempferol did not affect CYP3A1, but induced CYP1A2 in a dose-dependent manner. EGb 761 and the five individual constituents had no effects on rat CYP2D2, 2C11 and 2C7. 5. The results indicate that bilobalide, and to a lesser extent ginkgolide A, B, quercetin, and kaempferol, play a key role in the effects of EGb 761 on CYP induction. Further study is needed to elucidate the mechanism of CYP3A induction by EGb 761 and bilobalide.

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Author information

Author/s: Deng, Y (Y); Bi, H-C (HC); Zhao, L-Z (LZ); He, F (F); Liu, Y-Q (YQ); Yu, J-J (JJ); Ou, Z-M (ZM); Ding, L (L); Chen, X (X); Huang, Z-Y (ZY); Huang, M (M); Zhou, S-F (SF);

Affiliation: Institute of Clinical Pharmacology, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China.

Journal and publication information

Publication Type: Journal Article; Research Support, Non-U.S. Gov't

Journal: Xenobiotica; the fate of foreign compounds in biological systems (Xenobiotica), published in England. (Language: eng)

Reference: 2008-May; vol 38 (issue 5) : pp 465-81

Dates: Created 2008/04/18; Completed 2008/07/21;

PMID: 18421621, status: MEDLINE (last retrieval date: 11/6/2008)

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Animals
Cyclopentanes - pharmacology
Cytochrome P-450 Enzyme System - biosynthesis; genetics
Enzyme Induction - drug effects
Flavonoids - chemistry; pharmacology
Furans - pharmacology
Gene Expression - drug effects
Ginkgo biloba - chemistry
Ginkgolides - chemistry; pharmacology
Kaempferols - pharmacology

Kaempferols - pharmacology
Lactones - pharmacology
Male
Microsomes, Liver - drug effects; enzymology
Plant Extracts - chemistry; pharmacology
Quercetin - pharmacology
RNA, Messenger - genetics; metabolism
Rats
Rats, Sprague-Dawley
Reverse Transcriptase Polymerase Chain Reaction

Associated Chemicals: Cyclopentanes (0) ; Flavonoids (0) ; Furans (0) ; Ginkgo biloba extract 761 (0) ; Ginkgolides (0) ; Kaempferols (0) ; Lactones (0) ; Plant Extracts (0) ; RNA, Messenger (0) ; ginkgolide A (0) ; Quercetin (117-39-5) ; bilobalide (33570-04-6) ; kaempferol (520-18-3) ; Cytochrome P-450 Enzyme System (9035-51-2) ; ginkgolide B (99796-69-7)

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