RT Journal Article SR Electronic T1 DISTINCT ROLE OF BILOBALIDE AND GINKGOLIDE A IN THE MODULATION OF RAT CYP2B1 AND CYP3A23 GENE EXPRESSION BY GINKGO BILOBA EXTRACT IN CULTURED HEPATOCYTES JF Drug Metabolism and Disposition JO Drug Metab Dispos FD American Society for Pharmacology and Experimental Therapeutics SP 234 OP 242 DO 10.1124/dmd.105.005751 VO 34 IS 2 A1 Thomas K. H. Chang A1 Jie Chen A1 Xiao Wei Teng YR 2006 UL http://dmd.aspetjournals.org/content/34/2/234.abstract AB 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. The American Society for Pharmacology and Experimental Therapeutics