Intestinal and blood-brain barrier permeability of ginkgolides and bilobalide: in vitro and in vivo approaches.
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.
Madgula
Vamsi L M
VL
National Center for Natural Products Research, School of Pharmacy, The University of Mississippi, University, MS 38677, USA.
Avula
Bharathi
B
Yu
Young-Beob
YB
Wang
Yan-Hong
YH
Tchantchou
Flaubert
F
Fisher
Scott
S
Luo
Yuan
Y
Khan
Ikhlas A
IA
Khan
Shabana I
SI
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
D003517:Cyclopentanes; D005663:Furans; D046934:Ginkgolides; C073710:bilobalide