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Reduced Alzheimer’s disease pathology by St. John’s wort treatment is independent of hyperforin and facilitated by ABCC1 and microglia activation in mice


Year of Publication:
Contact PI Name:
Jens Pahnke
Contact PI Affiliation:
Neurodegeneration Research Lab (NRL), Department of Neurology, University of Magdeburg, Magdeburg, Germany
Jacqueline Hofrichter, Markus Krohn, Toni Schumacher, Cathleen Lange, Björn Feistel, Bernd Walbroel, Hans-Jochen Heinze, Sara Crockett, Timothy F. Sharbel
Primary Reference (PubMED ID):
Funding Source:
Not Reported
Study Goal and Principal Findings:

This study investigates effects of St. John's wort on cognition, Aβ levels, and microglial activation. Past studies have shown hyperforin, the main active constituent of St. John's wort, modulates the phagocytic activity of microglia. Other investigations indicate that hyperforin affects memory-enhancing properties in rodents. Hyperforin is a potent nuclear receptor ligand for PXR that leads to increased expression of the ATP binding cassette (ABC) transporter P glycoprotein, ABCB1, which is an ATP-dependent efflux pump with broad substrate specificity at the human BBB. Additionally, hyperforin inhibited P-glycoprotein transport activity in vitro, and enhanced the export activity of ABCB1 at the blood-brain barrier, and thus, reduce the concentration of intracerebral monomeric Aβ. Several studies have shown that ABCB1 contributes to Aβ clearance in mouse models and cell culture studies. Other studies demonstrated that another ABC transporter (ABCC1) has a strong influence on Aβ pathology in different mouse models. This study tested five extracts of SJW with variable hyperforin concentrations, to elucidate their effects on AD hallmarks and cognition in mice. Results demonstrate that extracts with low to negligible levels of hyperforin significantly improve memory performance and counteract neurodegeneration in vivo in a murine AD model. Oral administration of these extracts is highly effective at decreasing intracerebral Aβ42 levels and reducing Aβ plaques. These extracts do not only activate cerebral macrophages to improve phagocytosis rates by microglia, as confirmed in vitro and in vivo, but they additionally enhance ABCC1 transporter excretion of Aβ. Thus, SJW represents a viable treatment option for AD when special attention is paid to the extraction procedure of the plant material. 

Therapeutic Agent

Therapeutic Information:
Therapy Type:
Natural Product
Therapeutic Agent:
St. John's Wort
Therapeutic Target:
Multi Target

Animal Model

Model Information:
Model Type:
Strain/Genetic Background:
Not Reported

Experimental Design

Is the following information reported in the study?:
Power/Sample Size Calculation
Randomized into Groups
Blinded for Treatment
Blinded for Outcome Measures
Pharmacokinetic Measures
Pharmacodynamic Measures
Toxicology Measures
ADME Measures
Route of Delivery
Duration of Treatment
Frequency of Administration
Age of Animal at the Beginning of Treatment
Age of Animal at the End of Treatment
Sex as a Biological Variable
Study Balanced for Sex as a Biological Variable
Number of Premature Deaths
Number of Excluded Animals
Statistical Plan
Genetic Background
Inclusion/Exclusion Criteria Included
Conflict of Interest


Outcome Measured
Outcome Parameters
Morris Water Maze
beta Amyloid Load
Microglial Phagocytosis
ATP Binding Cassette Subfamily A Member 1 (ABCA1)
A Disintegrin and Metalloproteinase Domain 10 (ADAM10)
beta-Site Amyloid Precursor Protein Cleaving Enzyme 1 (BACE1)
Hyperforin/Hypericin Content
Brain-Buffer Soluble beta Amyloid Peptide 42
Brain-beta Amyloid Deposits
Neuronal Loss
Body Weight