St. John's Wort constituents modulate P-glycoprotein transport activity at the blood-brain barrier

Pharm Res. 2010 May;27(5):811-22. doi: 10.1007/s11095-010-0074-1. Epub 2010 Mar 13.


Purpose: The purpose of this study was to investigate the short-term signaling effects of St. John's Wort (SJW) extract and selected SJW constituents on the blood-brain barrier transporter P-glycoprotein and to describe the role of PKC in the signaling.

Methods: Cultured porcine brain capillary endothelial cells (PBCEC) and freshly isolated brain capillaries from pig were used as in vitro/ex vivo blood-brain barrier model. SJW modulation of P-glycoprotein function was studied in PBCEC using a calcein-AM uptake assay and in isolated pig brain capillaries using the fluorescent cyclosporine A derivative NBD-CSA and confocal microscopy.

Results: SJW extract and the constituents hyperforin, hypericin, and quercetin decreased P-glycoprotein transport activity in a dose- and time-dependent manner. SJW extract and hyperforin directly inhibited P-glycoprotein activity, whereas hypericin and quercetin modulated transporter function through a mechanism involving protein kinase C. Quercetin at high concentrations decreased P-glycoprotein transport activity, but increased transporter function at low concentrations. This increase in P-glycoprotein activity was likely due to trafficking and membrane insertion of vesicles containing transporter protein.

Conclusions: Our findings provide new insights into the short-term interaction of SJW with P-glycoprotein at the blood-brain barrier. They are of potential relevance given the wide use of SJW as OTC medication and the importance P-glycoprotein has for CNS therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism*
  • Animals
  • Biological Transport, Active / drug effects*
  • Blood-Brain Barrier / drug effects*
  • Blotting, Western
  • Capillaries / drug effects
  • Capillaries / metabolism
  • Cells, Cultured
  • Cyclosporine
  • Endothelial Cells / drug effects
  • Endothelial Cells / metabolism
  • Fluoresceins / metabolism
  • Fluorescent Dyes
  • Hypericum / chemistry*
  • Immunohistochemistry
  • In Vitro Techniques
  • Protein Kinase C / metabolism
  • Quercetin / pharmacology
  • Signal Transduction / drug effects
  • Swine


  • (N-5-(4-nitrobenzofurazan-7-yl)lysyl(8))cyclosporine
  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Fluoresceins
  • Fluorescent Dyes
  • calcein AM
  • Cyclosporine
  • Quercetin
  • Protein Kinase C