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.