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
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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.
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Article, publication date, and citation information can be found at http://dmd.aspetjournals.org.
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doi:10.1124/dmd.105.005751.
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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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