Transport of amentoflavone across the blood-brain barrier in vitro

Planta Med. 2002 Sep;68(9):804-7. doi: 10.1055/s-2002-34401.


The biflavone amentoflavone is an ingredient of Hypericum perforatum L. (Clusiaceae), a plant which is widely used for the treatment of mild to moderate depression. Amentoflavone inhibits the binding of flumazenil to the benzodiazepine binding site of the GABA A -receptor (IC(50) = 14.9 nM). Since it has to pass the blood-brain barrier (BBB) before reaching this receptor, the penetration of [(3)H]-amentoflavone through BBB was studied in an in vitro model consisting of primary cell cultures of porcine brain capillary endothelial cells (BCEC). Concentration-dependent uptake (37-2000 nM) was neither saturable nor temperature-sensitive indicating passive diffusion as the major uptake mechanism. This finding was confirmed by transport experiments through BCEC monolayers (> 2 % of applied dose was transported after 30 min). Co-administration of Hypericum extract increased amentoflavone transport significantly (amentoflavone alone: permeability coefficient P(app) = 4.59.10(-6) cm/s; co-administrated sucrose: P(app) = 3.22.10(-6)cm/s; amentoflavone together with hypericum: P(app) = 6.74.10(-6)cm/s, co-administrated sucrose P(app) = 5.49.10(-6)cm/s) indicating that Hypericum constituents enhance amentoflavone transport possibly by modulating paracellular permeability. Experiments with the P-glycoprotein (P-gp) overexpressing cell line P388-MDR showed that amentoflavone uptake was significantly enhanced by addition of the P-gp inhibitor verapamil, suggesting a P-gp mediated back-transport out of the cells. In conclusion, our findings show, that amentoflavone is able to pass the blood-brain barrier in vitro by passive diffusion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism
  • Animals
  • Biflavonoids*
  • Biological Transport / drug effects
  • Blood-Brain Barrier / drug effects*
  • Cells, Cultured
  • Dose-Response Relationship, Drug
  • Endothelium, Vascular / drug effects
  • Flavonoids / pharmacology*
  • Hypericum*
  • Plant Extracts / pharmacology
  • Swine
  • Tritium / metabolism
  • Tumor Cells, Cultured
  • Verapamil / pharmacology


  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Biflavonoids
  • Flavonoids
  • Plant Extracts
  • Tritium
  • amentoflavone
  • Verapamil