[Effects of various ginkgo biloba extracts and proanthocyanidin on hepatic cytochrome P450 activity in rats].
In previous papers, we showed that Ginkgo biloba extract (GBE) induced hepatic cytochrome P450 (CYP) activity, in particular pentoxyresorufin O-dealkylase (PROD; corresponding to CYP2B type) in rats, and that GBE influenced the efficacy of co-administered drugs. In this study, to clarify the nature of the induction, we examined the effects of GBE samples from different sources and some major constituents of GBE on rat hepatic CYP in vitro and in vivo. In the study in vitro, eight GBE samples dose-dependently inhibited PROD activity in microsomes prepared from GBE-treated rats, and the inhibitory ratio correlated well with the content of proanthocyanidin in the GBE samples. Moreover, among six GBE constituents examined, proanthocyanidin markedly inhibited the PROD activity. However, administration of two GBE extracts with different proanthocyanidin contents to rats induced hepatic CYP activity, including PROD, to similar extents, and proanthocyanidin alone did not induce PROD activity. Furthermore, GBE samples extracted with both acetone-water and ethanol-water showed similar induction of CYPs in rats in vivo. These results suggest that most GBE samples available in Japan induce CYPs in rats regardless of the preparation method of the GBE, and that proanthocyanidin is not responsible for the induction. Further studies will be necessary to identify the constituent(s) of GBE involved in the induction of CYPs in vivo.
Sugiyama
Tomomi
T
National Institute of Health and Nutrition, Tokyo, Japan.
Shinozuka
Kazumasa
K
Sano
Atsushi
A
Yamada
Shizuo
S
Endoh
Kaori
K
Yamada
Kazuhiko
K
Umegaki
Keizo
K
D000818:Animals; D002478:Cells, Cultured; D019362:Cytochrome P-450 CYP2B1 / Q000037:antagonists & inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004790:Enzyme Induction / Q000187:drug effects; D020441:Ginkgo biloba; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology*; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D044945:Proanthocyanidins / Q000032:analysis / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
D010936:Plant Extracts; D044945:Proanthocyanidins; C013221:proanthocyanidin; D003577:Cytochrome P-450 Enzyme System; D019362:Cytochrome P-450 CYP2B1