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Title: Intestinal and Blood-Brain Barrier Permeability of Ginkgolides and Bilobalide: In Vitro and In Vivo Approaches

item MADGULA, VAMSI - University Of Mississippi
item YU, YOUNG-BEOB - Korea Institute Of Oriental Medicine
item AVULA, BHARATHI - University Of Mississippi
item WANG, YAN - University Of Mississippi
item TCHANTCHOU, FLAUBERT - University Of Maryland
item FISHER, SCOTT - University Of Maryland
item LUO, YUAN - University Of Maryland
item KHAN, IKHLAS - University Of Mississippi
item KHAN, SHABANA - University Of Mississippi

Submitted to: Planta Medica
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/20/2009
Publication Date: 2/10/2010
Citation: Madgula, V.L., Yu, Y., Avula, B., Wang, Y.H., Tchantchou, F., Fisher, S., Luo, Y., Khan, I.A., Khan, S.I. 2010. Intestinal and Blood-Brain Barrier Permeability of Ginkgolides and Bilobalide: In Vitro and In Vivo Approaches. Planta Medica. 76:599-606.

Interpretive Summary: The manuscript entitled "Transport properties of Ginkgolides and Bilobalide in Caco-2 and MDR1-MDCK monolayer models" describes the usefulness of the Ginkgo biloba extract components when taken orally. The paper also explains the mechanism of action of molecules and how they reach into the body.

Technical Abstract: In this study intestinal and blood brain barrier (BBB) transport of ginkgolides A, B, C, J and bilobalide, isolated from Ginkgo biloba (Family-Ginkgoaceae), was evaluated in Caco-2 and MDR1-MDCK cell monolayer models. Transepithelial transport was examined for 2 hours in both absorptive and secretory directions. Quantitation was performed by UPLC-MS. In Caco-2 model, each compound (100µM) displayed a pH dependent transport in the absorptive direction. A low permeability of ginkgolides was observed across MDR1-MDCK model in the absorptive direction. The transport in the secretory direction was higher than the absorptive direction for all compounds in both models and efflux ratios were in the range of 1.5-3.6 in Caco-2 and > 10 in MDR1-MDCK model. In comparison to ginkgolides, permeability of bilobalide was much higher across Caco-2 monolayer in both directions. However, a poor transport of bilobalide was observed in 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 (8mg/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. In silico, Ginkgolides A, B, C, J and bilobalide were predicted to be moderate permeable compounds with intestinal permeability (PCaco-2) of 20 nm/sec and brain permeation (C brain/C blood) of 0.1 - 0.18.