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Research ArticleArticle

DISTINCT ROLE OF BILOBALIDE AND GINKGOLIDE A IN THE MODULATION OF RAT CYP2B1 AND CYP3A23 GENE EXPRESSION BY GINKGO BILOBA EXTRACT IN CULTURED HEPATOCYTES

Thomas K. H. Chang, Jie Chen and Xiao Wei Teng
Drug Metabolism and Disposition February 2006, 34 (2) 234-242; DOI: https://doi.org/10.1124/dmd.105.005751
Thomas K. H. Chang
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Jie Chen
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Xiao Wei Teng
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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 G. biloba extract also increased CYP3A2 and CYP3A18 mRNA expression in addition to CYP2B-mediated 7-benzyloxyresorufin O-dealkylation (BROD) and CYP3A-mediated testosterone 6β-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 a 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 to 5 μg/ml, bilobalide increased CYP2B1 mRNA and BROD, but not CYP3A23 mRNA or testosterone 6β-hydroxylation, whereas ginkgolide A increased CYP3A23 mRNA and testosterone 6β-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 G. biloba extract in primary cultures of rat hepatocytes.

Footnotes

  • This research was supported by the Canadian Institutes of Health Research (Grant MOP-42385 to T.K.H.C.) and a major equipment grant (to T.K.H.C.) from the Dawson Endowment Fund in Pharmaceutical Sciences. X.W.T. received a Postdoctoral Fellowship from the R&D Health Research Foundation/Canadian Institutes of Health Research and an Incentive Award from the Michael Smith Foundation for Health Research.

  • Article, publication date, and citation information can be found at http://dmd.aspetjournals.org.

  • doi:10.1124/dmd.105.005751.

  • ABBREVIATIONS: P450, cytochrome P450; BROD, 7-benzyloxyresorufin O-dealkylation; DEX, dexamethasone; DMSO, dimethyl sulfoxide; PB, phenobarbital; PCR, polymerase chain reaction.

    • Received May 31, 2005.
    • Accepted October 27, 2005.
  • The American Society for Pharmacology and Experimental Therapeutics
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Drug Metabolism and Disposition: 34 (2)
Drug Metabolism and Disposition
Vol. 34, Issue 2
1 Feb 2006
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DISTINCT ROLE OF BILOBALIDE AND GINKGOLIDE A IN THE MODULATION OF RAT CYP2B1 AND CYP3A23 GENE EXPRESSION BY GINKGO BILOBA EXTRACT IN CULTURED HEPATOCYTES
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Research ArticleArticle

DISTINCT ROLE OF BILOBALIDE AND GINKGOLIDE A IN THE MODULATION OF RAT CYP2B1 AND CYP3A23 GENE EXPRESSION BY GINKGO BILOBA EXTRACT IN CULTURED HEPATOCYTES

Thomas K. H. Chang, Jie Chen and Xiao Wei Teng
Drug Metabolism and Disposition February 1, 2006, 34 (2) 234-242; DOI: https://doi.org/10.1124/dmd.105.005751

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Research ArticleArticle

DISTINCT ROLE OF BILOBALIDE AND GINKGOLIDE A IN THE MODULATION OF RAT CYP2B1 AND CYP3A23 GENE EXPRESSION BY GINKGO BILOBA EXTRACT IN CULTURED HEPATOCYTES

Thomas K. H. Chang, Jie Chen and Xiao Wei Teng
Drug Metabolism and Disposition February 1, 2006, 34 (2) 234-242; DOI: https://doi.org/10.1124/dmd.105.005751
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