Pharmaceutical Research

, Volume 27, Issue 5, pp 811–822 | Cite as

St. John’s Wort Constituents Modulate P-glycoprotein Transport Activity at the Blood-Brain Barrier

  • Melanie Ott
  • Miriam Huls
  • Michael G. Cornelius
  • Gert FrickerEmail author
Research Paper



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.


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.


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.


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.


blood-brain barrier P-glycoprotein protein kinase C regulation St. John’s wort 







Porcine brain capillary endothelial cells


Protein kinase C


Phorbol 12-myristate 13-acetate


Pregnane X receptor




St. John’s wort



This study was supported by a Schlieben-Lange-Grant from the Ministry of Science, Research and the Arts Baden-Württemberg and the European Social Fund (to M.O.) and by a German Research Foundation grant GF1211/9-1 (to G.F.).



Supplementary material

11095_2010_74_MOESM1_ESM.pdf (18 kb)
ESM1 Supplemental Data (PDF 17 kb)


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Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Melanie Ott
    • 1
  • Miriam Huls
    • 2
  • Michael G. Cornelius
    • 3
  • Gert Fricker
    • 1
    Email author
  1. 1.Institute of Pharmacy and Molecular BiotechnologyRuprecht-Karls-University HeidelbergHeidelbergGermany
  2. 2.Department of Pharmacology and Toxicology, Nijmegen Centre for Molecular Life SciencesRadboud University Nijmegen Medical CentreNijmegenThe Netherlands
  3. 3.Department of Biosciences and NutritionKarolinska InstitutetHuddingeSweden

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