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Drug Metabolism and Disposition Fast Forward
First published on October 28, 2005; DOI: 10.1124/dmd.105.005751

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Received for publication June 1, 2005.
Revised September 14, 2005.
Accepted for publication October 27, 2005.

Distinct role of bilobalide and ginkgolide A in the modulation of rat CYP2B1 and CYP3A23 gene expression by Ginkgo biloba in cultured hepatocytes

Thomas K. H. Chang 1*, Jie Chen 1, Xiao Wei Teng 1

1 University of British Columbia

* Address correspondence to: E-mail: tchang{at}interchange.ubc.ca

Abstract

In the present study, primary cultures of rat hepatocytes were treated for 48 h with one of several extracts of Ginkgo biloba (10, 100, or 1000 µg/ml). Maximal increase in CYP2B1 and CYP3A23 mRNA levels was obtained at 100 µg/ml. This concentration of Ginkgo biloba extract also increased CYP3A2 and CYP3A18 mRNA expression in addition to CYP2B-mediated 7-benzyloxyresorufin O-dealkylation (BROD) and CYP3A-mediated testosterone 6{beta}-hydroxylation. In other experiments, cultured hepatocytes were treated for 48 h with bilobalide, ginkgolide A, ginkgolide B, ginkgolide C, ginkgolide J, kaempferol, quercetin, isorhamnetin, or a flavonol diglycoside at a concentration that represented the level present in an 100 µg/ml concentration of an extract. Only bilobalide (2.8 µg/ml) increased CYP2B1 mRNA expression and the fold-increase (7.9 ± 0.5; mean ± S.E.M.) was similar to that (8.3 ± 1.7) by the extract. By comparison, only ginkgolide A (1.1 µg/ml) increased CYP3A23 mRNA expression, but the extent (2.6 ± 0.5 fold) was less than the 5.3 ± 1.7 fold-increase by the extract. A greater concentration (5 µg/ml) of ginkgolide A was required to elevate CYP3A2 and CYP3A18 mRNA expression. Over the range of 1-5 µg/ml, bilobalide increased CYP2B1 mRNA and BROD, but not CYP3A23 mRNA or testosterone 6{beta}-hydroxylation, whereas ginkgolide A increased CYP3A23 mRNA and testosterone 6{beta}-hydroxylation, but not CYP2B1 mRNA or BROD. Overall, our novel results indicate a distinct role of bilobalide and ginkgolide A in the modulation of CYP2B1 and CYP3A23 gene expression and enzyme activities by Ginkgo biloba extract in primary cultures of rat hepatocytes.


Key words: CYP expression, CYP induction, CYP2B, CYP3A, hepatocytes


This article has been cited by other articles:


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 Drug Metab. Dispos.Home page
E. Y. H. Yeung, T. Sueyoshi, M. Negishi, and T. K. H. Chang
Identification of Ginkgo biloba as a Novel Activator of Pregnane X Receptor
Drug Metab. Dispos., November 1, 2008; 36(11): 2270 - 2276.
[Abstract] [Full Text] [PDF]


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