Differential role of ginkgolide A and bilobalide in CYP3A and CYP2B6 induction by Ginkgo biloba extract in primary cultures of human hepatocytes

Abstract

Ginkgo biloba extract and ginkgolide A induce CYP3A and CYP2B6 in human hepatocytes, but conflicting data exist for the effect of bilobalide on CYP3A expression. Also, it is unknown which chemicals contribute to these effects by the extract. We assessed in human hepatocytes the role of ginkgolide A and bilobalide in the modulation of CYP3A and CYP2B6 expression by G. biloba extract, and compared the effect of the extract and chemicals on these enzymes. As analyzed by HPLC, LC‐MS, and real‐time PCR, control analysis indicated that rifampicin increased CYP3A‐mediated testosterone 6β‐hydroxylation and CYP3A4 mRNA levels, and CITCO increased CYP2B6‐mediated bupropion hydroxylation and CYP2B6 mRNA levels. G. biloba extract (25–200 μg/ml) induced CYP3A to a greater extent than CYP2B6. At a level present in 100 μg/ml of extract, ginkgolide A (1.1 μg/ml) increased CYP3A but not CYP2B6 expression, whereas bilobalide (2.8 μg/ml) had no effect. Ginkgolide A (1.1–10 μg/ml) induced CYP3A to a greater extent than CYP2B6, but bilobalide (5–20 μg/ml) induced both enzymes to a similar extent. CYP3A induction by bilobalide was less than that by ginkgolide A. In summary, G. biloba extract, ginkgolide A, and bilobalide differentially induced CYP3A and CYP2B6. Among the two chemicals, only ginkgolide A contributed to CYP3A induction by the extract, whereas neither of them accounted for CYP2B6 induction. [Supported by CIHR and MSFHR]