St. John's Wort Reduces Beta-Amyloid Accumulation in a Double Transgenic Alzheimer's Disease Mouse Model—Role of P-Glycoprotein

Authors

  • Anja Brenn,

    1. Department of Neuropathology, Institute of Pathology, University of Greifswald, Greifswald, Germany
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  • Markus Grube,

    1. Department of Pharmacology, Center of Drug Absorption and Transport (C_DAT), University of Greifswald, Greifswald, Germany
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  • Gabriele Jedlitschky,

    1. Department of Pharmacology, Center of Drug Absorption and Transport (C_DAT), University of Greifswald, Greifswald, Germany
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  • Andrea Fischer,

    1. Department of Pharmacology, Center of Drug Absorption and Transport (C_DAT), University of Greifswald, Greifswald, Germany
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  • Barbara Strohmeier,

    1. Friedrich-Loeffler-Institute, Institute for Novel and Emerging Infectious Diseases, Federal Research Institute for Animal Health, Greifswald-Insel Riems, Germany
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  • Martin Eiden,

    1. Friedrich-Loeffler-Institute, Institute for Novel and Emerging Infectious Diseases, Federal Research Institute for Animal Health, Greifswald-Insel Riems, Germany
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  • Markus Keller,

    1. Friedrich-Loeffler-Institute, Institute for Novel and Emerging Infectious Diseases, Federal Research Institute for Animal Health, Greifswald-Insel Riems, Germany
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  • Martin H. Groschup,

    1. Friedrich-Loeffler-Institute, Institute for Novel and Emerging Infectious Diseases, Federal Research Institute for Animal Health, Greifswald-Insel Riems, Germany
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  • Silke Vogelgesang

    Corresponding author
    1. Department of Neuropathology, Institute of Pathology, University of Greifswald, Greifswald, Germany
    • Corresponding author:

      Silke Vogelgesang, MD, Department of Neuropathology, Ernst-Moritz-Arndt University, Friedrich-Loeffler-Str. 23e, D-17487 Greifswald, Germany (E-mail: sivogelg@uni-greifswald.de)

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Abstract

The adenosine triphosphate-binding cassette transport protein P-glycoprotein (ABCB1) is involved in the export of beta-amyloid from the brain into the blood, and there is evidence that age-associated deficits in cerebral P-glycoprotein content may be involved in Alzheimer's disease pathogenesis. P-glycoprotein function and expression can be pharmacologically induced by a variety of compounds including extracts of Hypericum perforatum (St. John's Wort). To clarify the effect of St. John's Wort on the accumulation of beta-amyloid and P-glycoprotein expression in the brain, St. John's Wort extract (final hyperforin concentration 5%) was fed to 30-day-old male C57BL/6J-APP/PS1+/− mice over a period of 60 or 120 days, respectively. Age-matched male C57BL/6J-APP/PS1+/− mice receiving a St. John's Wort-free diet served as controls. Mice receiving St. John's Wort extract showed (i) significant reductions of parenchymal beta-amyloid 1–40 and 1–42 accumulation; and (ii) moderate, but statistically significant increases in cerebrovascular P-glycoprotein expression. Thus, the induction of cerebrovascular P-glycoprotein may be a novel therapeutic strategy to protect the brain from beta-amyloid accumulation, and thereby impede the progression of Alzheimer's disease.

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