Reduced Alzheimer’s Disease Pathology by St. John’s Wort Treatment is Independent of Hyperforin and Facilitated by ABCC1 and Microglia Activation in Mice

Title:Reduced Alzheimer’s Disease Pathology by St. John’s Wort Treatment is Independent of Hyperforin and Facilitated by ABCC1 and Microglia Activation in Mice

Volume: 10 Issue: 10

Author(s): Jacqueline Hofrichter, Markus Krohn, Toni Schumacher, Cathleen Lange, Björn Feistel, Bernd Walbroel, Hans-Jochen Heinze, Sara Crockett, Timothy F.Sharbel and Jens Pahnke

Affiliation:

Keywords: Alzheimer’s disease, ABC transporters, ABCC1, blood-brain barrier, β-amyloid clearance, hyperforin, Hypericumperforatum, St. John’s wort.

Abstract: Soluble β-amyloid peptides (Aβ) and small Aβ oligomers represent the most toxic peptide moieties recognized in brains affected by Alzheimer’s disease (AD). Here we provide the first evidence that specific St. John’s wort (SJW) extracts both attenuate Aβ-induced histopathology and alleviate memory impairments in APP-transgenic mice. Importantly, these effects are attained independently of hyperforin. Specifically, two extracts characterized by low hyperforin content (i) significantly decrease intracerebral Aβ₄₂ levels, (ii) decrease the number and size of amyloid plaques, (iii) rescue neocortical neurons, (iv) restore cognition to normal levels, and (iv) activate microglia in vitro and in vivo. Mechanistically, we reveal that the reduction of soluble Aβ₄₂ species is the consequence of a highly increased export activity in the bloodbrain barrier ABCC1transporter, which was found to play a fundamental role in Aβ excretion into the bloodstream. These data (i) support the significant beneficial potential of SJW extracts on AD proteopathy, and (ii) demonstrate for the first time that hyperforin concentration does not necessarily correlate with their therapeutic effects. Hence, by activating ABC transporters, specific extracts of SJW may be used to treat AD and other diseases involving peptide accumulation and cognition impairment. We propose that the anti-depressant and anti-dementia effects of these hyperforin-reduced phytoextracts could be combined for treatment of the elderly, with a concomitant reduction in deleterious hyperforin-related side effects.

Cite this article as:

Hofrichter Jacqueline, Krohn Markus, Schumacher Toni, Lange Cathleen, Feistel Björn, Walbroel Bernd, Heinze Hans-Jochen, Crockett Sara, F.Sharbel Timothy and Pahnke Jens, 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 2013; 10 (10) . https://dx.doi.org/10.2174/15672050113106660171