title: Ginkgo biloba extract attenuates warfarin-mediated anticoagulation through induction of hepatic cytochrome P450 enzymes by bilobalide in mice.
abstract: Ginkgo biloba extract (GBE) is a popular herbal ingredient used worldwide, but it is reported to induce bleeding as a serious adverse event. In this study we examined whether GBE induced spontaneous bleeding or accelerated warfarin anticoagulation via herb-drug interaction. Mice were given GBE or various active components of GBE orally for 5 days and blood coagulation parameters and hepatic cytochrome P450 enzymes (CYPs) were measured. Mice also received warfarin (racemate, (S)- or (R)-enantiomer) for the last 3 days of the 5-day regimen to examine GBE-warfarin interactions. Neither GBE (up to 1000 mg/kg) nor ginkgolide B (up to 140 mg/kg), a platelet-activating factor antagonist, influenced blood coagulation parameters. In contrast, GBE attenuated the anticoagulant action of warfarin. Bilobalide, a component of GBE that markedly induced hepatic CYPs including (S)-warfarin hydroxylase, showed similar effects. For (S)-warfarin, the anticoagulation action and the interaction with GBE was clear, while the influence on metabolism was greater for (R)-warfarin than for (S)-warfarin, which corresponded to the CYP types induced by GBE. These results suggest that GBE and ginkgolide B have no influence on blood coagulation in vivo, and that GBE attenuates the anticoagulation action of warfarin via induction of hepatic CYPs by bilobalide.
authors.affiliation: National Institute of Health and Nutrition, Tokyo, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Taki
authors.forename: Kaori
authors.initials: K
authors.lastname: Yokotani
authors.forename: Shizuo
authors.initials: S
authors.lastname: Yamada
authors.forename: Kazumasa
authors.initials: K
authors.lastname: Shinozuka
authors.forename: Yoko
authors.initials: Y
authors.lastname: Kubota
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Watanabe
authors.forename: Keizo
authors.initials: K
authors.lastname: Umegaki
mesh_terms: D000818:Animals; D000925:Anticoagulants / Q000009:adverse effects*; D001777:Blood Coagulation / Q000187:drug effects; D003029:Coagulants / Q000494:pharmacology; D003517:Cyclopentanes / Q000008:administration & dosage / Q000494:pharmacology*; D003577:Cytochrome P-450 Enzyme System / Q000737:chemistry* / Q000187:drug effects; D004790:Enzyme Induction; D005663:Furans / Q000008:administration & dosage / Q000494:pharmacology*; D020441:Ginkgo biloba / Q000737:chemistry*; D046934:Ginkgolides / Q000008:administration & dosage / Q000494:pharmacology*; D041743:Herb-Drug Interactions; D007783:Lactones / Q000008:administration & dosage / Q000494:pharmacology; D008099:Liver / Q000737:chemistry / Q000187:drug effects; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D010936:Plant Extracts / Q000008:administration & dosage / Q000494:pharmacology*; D014859:Warfarin / Q000008:administration & dosage / Q000009:adverse effects*
chemical_list: D000925:Anticoagulants; D003029:Coagulants; D003517:Cyclopentanes; D005663:Furans; D046934:Ginkgolides; D007783:Lactones; D010936:Plant Extracts; D014859:Warfarin; D003577:Cytochrome P-450 Enzyme System; C045856:ginkgolide B; C073710:bilobalide