ArticlePharmaceutical research2010
St. John's Wort constituents modulate P-glycoprotein transport activity at the blood-brain barrier.
Article in Pharmaceutical research, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 45 citations in OpenAlex.
- Influence of St. John's Wort on Intravenous Fentanyl Pharmacokinetics, Pharmacodynamics, and Clinical Effects: A Randomized Clinical Trial.Anesthesiology · 2020Trial
- St. John's Wort Extract Increases Pgp Expression in the Brain but Not in the Small Intestine or the Liver of Wistar Rats.Pharmacology research & perspectives · 2025Article
- Much More than Nutrients: The Protective Effects of Nutraceuticals on the Blood-Brain Barrier in Diseases.Nutrients · 2025Review
- St. John's wort extract with a high hyperforin content does not induce P-glycoprotein activity at the human blood-brain barrier.Clinical and translational science · 2024Article
- Novel Intrinsic Mechanisms of Active Drug Extrusion at the Blood-Brain Barrier: Potential Targets for Enhancing Drug Delivery to the Brain?Pharmaceutics · 2020Review
- Antibody-Based Immunotherapy: Alternative Approaches for the Treatment of Metastatic Melanoma.Biomedicines · 2020Review
- Clinical relevance of St. John's wort drug interactions revisited.British journal of pharmacology · 2020Review
- Synthesis and Characterization of Bodipy-FL-Cyclosporine A as a Substrate for Multidrug Resistance-Linked P-Glycoprotein (ABCB1).Drug metabolism and disposition: the biological fate of chemicals · 2019Article
- Protein Kinases C-Mediated Regulations of Drug Transporter Activity, Localization and Expression.International journal of molecular sciences · 2017Review
- Hypericum Perforatum Hydroalcoholic Extract Mitigates Motor Dysfunction and is Neuroprotective in Intrastriatal 6-Hydroxydopamine Rat Model of Parkinson's Disease.Cellular and molecular neurobiology · 2016Article
- Pregnane X Receptor and P-glycoprotein: a connexion for Alzheimer's disease management.Molecular diversity · 2014Review
- St. John's Wort reduces beta-amyloid accumulation in a double transgenic Alzheimer's disease mouse model-role of P-glycoprotein.Brain pathology (Zurich, Switzerland) · 2014Article
- Drug-induced trafficking of p-glycoprotein in human brain capillary endothelial cells as demonstrated by exposure to mitomycin C.PloS one · 2014Article
- Reduced Alzheimer's disease pathology by St. John's Wort treatment is independent of hyperforin and facilitated by ABCC1 and microglia activation in mice.Current Alzheimer research · 2013Article
- Development of quercetin nanoformulation and in vivo evaluation using streptozotocin induced diabetic rat model.Drug delivery and translational research · 2012Article
- Drug interactions with herbal medicines.Clinical pharmacokinetics · 2012Review
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeThe 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.
methodsCultured 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.
resultsSJW 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.
conclusionsOur 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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.