title: Bilobalide in Ginkgo biloba extract is a major substance inducing hepatic CYPs.
abstract: In a search for substances related to the marked induction of hepatic cytochrome P450 (CYP) by ginkgo biloba extract (GBE), mice were given either GBE (1000 mg kg(-1)) or fractions of GBE for 5 days. The content and activity of CYPs were induced markedly by a bilobalide-rich fraction, but not by flavonoid-rich fractions. The level of induction by the bilobalide-rich fraction was almost the same as that induced by the unfractionated GBE, suggesting that bilobalide is largely responsible for the CYPs induction. To confirm these findings, mice were given various doses of bilobalide (10.5, 21 and 42 mg kg(-1)), or GBE (1000 mg kg(-1), containing bilobalide at 42 mg kg(-1)). Treatment with bilobalide induced CYPs markedly and in a dose-dependent manner, and the level of induction was quite similar between bilobalide (42 mg kg(-1)) and GBE. Treatment with GBE and with bilobalide greatly induced pentoxyresorufin O-dealkylase activity. These findings indicate that bilobalide is the major substance in GBE that induces hepatic CYPs.
authors.affiliation: National Institute of Health and Nutrition, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8636, Japan. umegaki@nih.go.jp
authors.forename: Keizo
authors.initials: K
authors.lastname: Umegaki
authors.forename: Yuko
authors.initials: Y
authors.lastname: Taki
authors.forename: Kaori
authors.initials: K
authors.lastname: Endoh
authors.forename: Kyoko
authors.initials: K
authors.lastname: Taku
authors.forename: Hiroki
authors.initials: H
authors.lastname: Tanabe
authors.forename: Kazumasa
authors.initials: K
authors.lastname: Shinozuka
authors.forename: Tomomi
authors.initials: T
authors.lastname: Sugiyama
mesh_terms: D000818:Animals; D003517:Cyclopentanes / Q000008:administration & dosage / Q000494:pharmacology*; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D004790:Enzyme Induction; D005663:Furans / Q000008:administration & dosage / Q000494:pharmacology*; D020441:Ginkgo biloba; D046934:Ginkgolides / Q000008:administration & dosage / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008862:Microsomes, Liver / Q000187:drug effects* / Q000201:enzymology; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology
chemical_list: D003517:Cyclopentanes; D005663:Furans; D046934:Ginkgolides; D010936:Plant Extracts; D003577:Cytochrome P-450 Enzyme System; C073710:bilobalide