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Planta Med 2013; 79(16): 1545-1551
DOI: 10.1055/s-0033-1350797
Pharmacokinetic Investigations
Original Papers
Georg Thieme Verlag KG Stuttgart · New York

In vitro Permeability Study of CNS-Active Diterpenes from Sideritis spp. Using Cellular Models of Blood-Brain Barrier

Elena González-Burgos
Department of Pharmacology, Faculty of Pharmacy, University Complutense, Madrid, Spain
,
M. Emilia Carretero
Department of Pharmacology, Faculty of Pharmacy, University Complutense, Madrid, Spain
,
M. Pilar Gómez-Serranillos
Department of Pharmacology, Faculty of Pharmacy, University Complutense, Madrid, Spain
› Author Affiliations
Further Information

Publication History

received 16 May 2013
revised 01 August 2013

accepted 07 August 2013

Publication Date:
12 September 2013 (online)

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Abstract

The major diterpenes andalusol, conchitriol, foliol, lagascatriol, linearol, and sidol, isolated from Sideritis spp., have been recently identified as neuroprotective agents. In this study, the blood brain-barrier permeability characteristics of these natural compounds were investigated for the first time using in silico and in vitro (RBE4 monocultures and ECV304/C6 co-cultures) methods. Computational tools revealed that these diterpenes have a favorable permeability profile to pass across the blood brain-barrier. In the RBE4 cell model, used for uptake studies, all compounds were taken up in a concentration and time-dependent manner. A bidirectional transport of diterpenes was observed across the ECV304/C6 co-culture model, with Papp values in the range of 3.7 × 10−6 cm/sec and 9.5 × 10−6 cm/sec for foliol and andalusol, respectively. Andalusol and lagascatriol were the most efficiently in being taken up and transported across the established blood brain-barrier in vitro model. These findings suggest that the investigated compounds from Sideritis spp. may predominantly move across the blood brain-barrier by passive diffusion. The observations have implications for understanding how CNS-active diterpenes enter the brain endothelium and traverse the blood brain-barrier, and thus exert their neuroprotective actions.

Key words

blood brain-barrier - diterpenes - Sideritis - Lamiaceae - passive diffusion
 

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