title: Intestinal and blood-brain barrier permeability of ginkgolides and bilobalide: in vitro and in vivo approaches.
abstract: In this study intestinal and blood-brain barrier (BBB) permeability of ginkgolides A, B, C, J and bilobalide, isolated from Ginkgo biloba (Ginkgoaceae), was evaluated in Caco-2 and MDR1-MDCK cell monolayer models. The transport was examined for 2 hours in both absorptive and secretory directions. Quantitation was performed by UPLC-MS. In the Caco-2 model, each compound (100 microM) displayed a pH-dependent transport in the absorptive direction. A low permeability of ginkgolides was observed across the MDR1-MDCK model in the absorptive direction. An efflux was observed for all compounds in both the models. The efflux ratio was much higher in the MDR1-MDCK cell model (> 10) compared to the Caco-2 cell model (1.5-3.6). In comparison to ginkgolides, the permeability of bilobalide was much higher across the Caco-2 monolayer in both directions. However, a poor transport of bilobalide was observed in the MDR1-MDCK model in the absorptive direction. A high efflux was observed for all compounds in the mixture form as compared to their isolated forms. In rats, a single dose of bilobalide (8 mg/kg) administered intravenously resulted in a significant level of bilobalide in both plasma and brain. A brain-to-plasma partition coefficient of 0.56 at 120 min indicated its possibility of brain uptake.
authors: National Center for Natural Products Research, School of Pharmacy, The University of Mississippi, University, MS 38677, USA.
authors: Vamsi L M
authors: VL
authors: Madgula
authors: Bharathi
authors: B
authors: Avula
authors: Young-Beob
authors: YB
authors: Yu
authors: Yan-Hong
authors: YH
authors: Wang
authors: Flaubert
authors: F
authors: Tchantchou
authors: Scott
authors: S
authors: Fisher
authors: Yuan
authors: Y
authors: Luo
authors: Ikhlas A
authors: IA
authors: Khan
authors: Shabana I
authors: SI
authors: Khan
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects*; D002460:Cell Line; D003517:Cyclopentanes / Q000737:chemistry / Q000494:pharmacology*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005663:Furans / Q000737:chemistry / Q000494:pharmacology*; D046934:Ginkgolides / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D007422:Intestines / Q000187:drug effects*; D015394:Molecular Structure; D051381:Rats
chemical_list: D003517:Cyclopentanes; D005663:Furans; D046934:Ginkgolides; C073710:bilobalide