Planta Med 2010; 76(6): 599-606
DOI: 10.1055/s-0029-1240601
Pharmacology
Original Papers
© Georg Thieme Verlag KG Stuttgart · New York

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

Vamsi L. M. Madgula1 , Bharathi Avula1 , Young-Beob Yu3 , 5 , Yan-Hong Wang1 , Flaubert Tchantchou3 , Scott Fisher3 , Yuan Luo3 , 4 , Ikhlas A. Khan1 , 2 , Shabana I. Khan1 , 2
  • 1National Center for Natural Products Research, School of Pharmacy, The University of Mississippi, University, MS, USA
  • 2Department of Pharmacognosy, School of Pharmacy, The University of Mississippi, University, MS, USA
  • 3Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland, Baltimore, MD, USA
  • 4Center for Integrative Medicine, Department of Medicine, University of Maryland, Baltimore, MD, USA
  • 5Present address: Department of Herbal Pharmaceutical Development, Korea Institute of Oriental Medicine, Daejeon, Korea
Further Information

Publication History

received May 28, 2009 revised October 5, 2009

accepted October 20, 2009

Publication Date:
20 November 2009 (online)

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 µM) 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.

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Shabana I. Khan

School of Pharmacy
National Center for Natural Products Research
University of Mississippi

University, MS 38677

USA

Phone: + 1 66 29 15 10 41

Fax: + 1 66 29 15 70 62

Email: skhan@olemiss.edu

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