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Cellular and Molecular Neurobiology

, Volume 31, Issue 5, pp 787–793 | Cite as

The Blood–Brain Barrier Permeability of Geissoschizine Methyl Ether in Uncaria Hook, a Galenical Constituent of the Traditional Japanese Medicine Yokukansan

  • Sachiko Imamura
  • Masahiro Tabuchi
  • Hirotaka Kushida
  • Akinori Nishi
  • Hitomi Kanno
  • Takuji Yamaguchi
  • Kyoji Sekiguchi
  • Yasushi Ikarashi
  • Yoshio Kase
Original Research

Abstract

Geissoschizine methyl ether (GM) in Uncaria hook, a galenical constituent of yokukansan is thought to be one of active components in the psychotropic effect of yokukansan, a traditional Japanese medicine (kampo medicine). However, there is no data on the blood–brain barrier (BBB) permeability of Uncaria hook-derived alkaloids containing GM. In this study, we investigated the BBB permeability of seven Uncaria hook alkaloids (GM, isocorynoxeine, isorhynchophylline, hirsuteine, hirsutine, rhynchophylline, and corynoxeine) using in vivo and in vitro methods. In the in vivo experiment, seven alkaloids in the plasma and brain of rats orally administered with yokukansan were measured by liquid chromatography–mass spectroscopy/mass spectrometric multiple reaction monitoring assay. In the in vitro experiment, the BBB permeability of seven alkaloids were examined using the BBB model composed of co-culture of endothelial cells, pericytes, and astrocytes. In the in vivo study, six components containing GM but not isocorynoxeine were detected in the plasma, and three (GM, hirsuteine, and corynoxeine) of components were detected in the brain. The in vitro BBB permeability data indicated that seven alkaloids were able to cross brain endothelial cells in culture conditions and that the BBB permeability of GM was higher than those of the other six alkaloids. These results suggest that target ingredient GM in yokukansan administered orally is absorbed into the blood and then reaches the brain through the BBB. This evidence further supports the possibility that GM is an active component in the psychotropic effect of yokukansan.

Keywords

Blood–brain barrier Geissoschizine methyl ether Uncaria hook Yokukansan 

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Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Sachiko Imamura
    • 1
  • Masahiro Tabuchi
    • 1
  • Hirotaka Kushida
    • 1
  • Akinori Nishi
    • 1
  • Hitomi Kanno
    • 1
  • Takuji Yamaguchi
    • 1
  • Kyoji Sekiguchi
    • 1
  • Yasushi Ikarashi
    • 1
  • Yoshio Kase
    • 1
  1. 1.Tsumura Research LaboratoriesTsumura & CoIbarakiJapan

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