In vitro and in vivo study of CJY, an isoflavone, on p-glycoprotein function in rats

J Chemother. 2008 Jun;20(3):361-7. doi: 10.1179/joc.2008.20.3.361.

Abstract

The p-glycoprotein is a transmembrane efflux transporter found on the luminal side of the capillary endothelial cells that comprise the blood-brain barrier. This study examined the effect of CJY, an isoflavone, on the levels of a p-glycoprotein substrate, rhodamine123 (Rh123), in rat brain microvessel endothelial cells (RBMEC) and in rat brain homogenate using fluorescence spectrophotometer and high performance liquid chromatography, respectively. In the in vitro study, incubation of RBMEC cells with CJY caused a marked increase in uptake and a notable decrease in efflux of Rh123. The inhibitory effect of the agent on P-gp function was reversible and remained even after the 2.5microM agent was removed from the medium for 120 min. In the in vivo study, CJY also elevated the Rh123 levels in rat brain homogenate after the rats received a 0.45 mg/kg dose of the CJY by slow intravenous injection, indicating that CJY may be a candidate as a p-glycoprotein inhibitor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / antagonists & inhibitors*
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism
  • Animals
  • Brain / blood supply
  • Brain / drug effects
  • Brain / metabolism
  • Capillaries / cytology
  • Capillaries / drug effects
  • Capillaries / metabolism
  • Cells, Cultured
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / metabolism
  • Humans
  • Isoflavones / pharmacology*
  • Rats
  • Rhodamine 123 / metabolism

Substances

  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • CJY compound
  • Isoflavones
  • Rhodamine 123