INDUCTION OF CYP3A IN PRIMARY CULTURES OF HUMAN HEPATOCYTES BY GINKGOLIDES A AND B.

1. The present study was designed to determine the effects of ginkgolide A, ginkgolide B and quercetin on CYP3A protein expression and enzyme activity in primary cultures of human hepatocytes. 2. Hepatocytes were pretreated with ginkgolide A, ginkgolide B and quercetin (at 1, 3, 10 and 30 µmol/L) for 48 h and then exposed to testosterone (250 µmol/L) for 30 min. Rifampin (10 µmol/L) and phenobarbital (2 mmol/L) were used as positive controls. The CYP3A activity was measured by the amount of 6β-hydroxytestosterone in the culture medium and CYP3A protein in hepatocyte lysate was semiquantified by immunoblotting. 3. Compared with the vehicle control, ginkgolides A and B, at 30 µmol/L, significantly induced CYP3A protein expression (2.1- and 2-fold, respectively; both P < 0.01) and markedly induced CYP3A-mediated testosterone 6β-hydroxylation (2.5-fold each; P < 0.05 for ginkgolide A; P > 0.05 for ginkgolide B). Quercetin had no apparent induction. 4. Ginkgolide A and ginkgolide B can induce CYP3A protein expression and enzyme activity in primary cultures of human hepatocytes at higher doses. [ABSTRACT FROM AUTHOR]