1. Reduced Alzheimer’s Disease Pathology by St. John’s Wort Treatment is Independent of Hyperforin and Facilitated by ABCC1 and Microglia Activation in Mice
- Author
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Bernd Walbroel, Cathleen Lange, Björn Feistel, Toni Schumacher, Hans-Jochen Heinze, Timothy F. Sharbel, Sara Crockett, Jens Pahnke, Jacqueline Hofrichter, and Markus Krohn
- Subjects
Time Factors ,multidrug resistance-associated protein 1 ,Plaque, Amyloid ,genetics [Alzheimer Disease] ,ATP-binding cassette transporter ,drug effects [Gene Expression Regulation] ,Pharmacology ,drug effects [Microglia] ,medicine.disease_cause ,law.invention ,pathology [Alzheimer Disease] ,Mice ,Amyloid beta-Protein Precursor ,chemistry.chemical_compound ,pathology [Brain] ,law ,drug therapy [Plaque, Amyloid] ,hyperforin ,drug therapy [Alzheimer Disease] ,metabolism [Peptide Fragments] ,analogs & derivatives [Phloroglucinol] ,chemistry [Hypericum] ,Phagocytes ,drug effects [Phagocytes] ,Microglia ,Proteopathy ,Brain ,complications [Alzheimer Disease] ,etiology [Plaque, Amyloid] ,amyloid beta-protein (1-42) ,medicine.anatomical_structure ,Neurology ,genetics [Amyloid beta-Protein Precursor] ,pharmacology [Peptide Fragments] ,drug effects [Brain] ,Multidrug Resistance-Associated Proteins ,therapeutic use [Phloroglucinol] ,Hypericum ,therapeutic use [Terpenes] ,Transgene ,metabolism [Amyloid beta-Peptides] ,Mice, Transgenic ,therapeutic use [Plant Preparations] ,Phloroglucinol ,Biology ,drug effects [Maze Learning] ,Article ,Alzheimer Disease ,In vivo ,medicine ,Animals ,ddc:610 ,Maze Learning ,metabolism [Multidrug Resistance-Associated Proteins] ,chemistry [Plant Preparations] ,Amyloid beta-Peptides ,Dose-Response Relationship, Drug ,Terpenes ,Peptide Fragments ,In vitro ,Disease Models, Animal ,Hyperforin ,Gene Expression Regulation ,chemistry ,metabolism [Brain] ,pharmacology [Amyloid beta-Peptides] ,Plant Preparations ,Neurology (clinical) ,Phytotherapy - Abstract
Soluble β -amyloid peptides (A β) 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 A β-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 Aβ 42 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 Aβ 42 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.
- Published
- 2013
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