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

0090-9556/06/3402-234-242$20.00
DMD 34:234-242, 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

Thomas K. H. Chang, Jie Chen, and Xiao Wei Teng

Faculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver, British Columbia, Canada

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 6ß-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 6ß-hydroxylation, whereas ginkgolide A increased CYP3A23 mRNA and testosterone 6ß-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.

Address correspondence to: Dr. Thomas K. H. Chang, Faculty of Pharmaceutical Sciences, The University of British Columbia, 2146 East Mall, Vancouver, BC, V6T 1Z3, Canada. E-mail: tchang{at}interchange.ubc.ca




This article has been cited by other articles:


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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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