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Apolar Extracts of St. John’s Wort Alleviate the Effects of β-Amyloid Toxicity in Early Alzheimer’s Disease

GND
122581653X
Affiliation
Julius Kühn Institute (JKI), Institute for Breeding Research on Horticultural Crops, Germany; Translational Neurodegeneration Research and Neuropathology Lab/Section of Neuropathology Research, Department of Pathology, Medical Faculty/KlinMED, University of Oslo (UiO) and Oslo University Hospital (OUS), Sognsvannsveien 20, 0372 Oslo, Norway
El Menuawy, Ahmed;
ORCID
0000-0002-7060-6564
Affiliation
Translational Neurodegeneration Research and Neuropathology Lab/Section of Neuropathology Research, Department of Pathology, Medical Faculty/KlinMED, University of Oslo (UiO) and Oslo University Hospital (OUS), Sognsvannsveien 20, 0372 Oslo, Norway
Brüning, Thomas;
Affiliation
Translational Neurodegeneration Research and Neuropathology Lab/Section of Neuropathology Research, Department of Pathology, Medical Faculty/KlinMED, University of Oslo (UiO) and Oslo University Hospital (OUS), Sognsvannsveien 20, 0372 Oslo, Norway
Eiriz, Iván;
GND
1225815193
Affiliation
Julius Kühn Institute (JKI), Institute for Breeding Research on Horticultural Crops, Germany
Hähnel, Urs;
GND
173016197
ORCID
0000-0001-9025-7560
Affiliation
Julius Kühn Institute (JKI), Institute for Breeding Research on Horticultural Crops, Germany
Marthe, Frank;
GND
1112749756
Affiliation
Translational Neurodegeneration Research and Neuropathology Lab/Section of Neuropathology Research, Department of Pathology, Medical Faculty/KlinMED, University of Oslo (UiO) and Oslo University Hospital (OUS), Sognsvannsveien 20, 0372 Oslo, Norway
Möhle, Luisa;
Affiliation
Translational Neurodegeneration Research and Neuropathology Lab/Section of Neuropathology Research, Department of Pathology, Medical Faculty/KlinMED, University of Oslo (UiO) and Oslo University Hospital (OUS), Sognsvannsveien 20, 0372 Oslo, Norway
Górska, Anna Maria;
Affiliation
Translational Neurodegeneration Research and Neuropathology Lab/Section of Neuropathology Research, Department of Pathology, Medical Faculty/KlinMED, University of Oslo (UiO) and Oslo University Hospital (OUS), Sognsvannsveien 20, 0372 Oslo, Norway
Santos-García, Irene;
ORCID
0000-0001-6026-863X
Affiliation
Section for Pharmaceutical Chemistry, Department of Pharmacy, University of Oslo (UiO), Sem Sælands vei 3, 0371 Oslo, Norway
Wangensteen, Helle;
Affiliation
Translational Neurodegeneration Research and Neuropathology Lab/Section of Neuropathology Research, Department of Pathology, Medical Faculty/KlinMED, University of Oslo (UiO) and Oslo University Hospital (OUS), Sognsvannsveien 20, 0372 Oslo, Norway
Wu, Jingyun;
GND
123028566
ORCID
0000-0001-7355-4213
Affiliation
Translational Neurodegeneration Research and Neuropathology Lab/Section of Neuropathology Research, Department of Pathology, Medical Faculty/KlinMED, University of Oslo (UiO) and Oslo University Hospital (OUS), Sognsvannsveien 20, 0372 Oslo, Norway; Institute of Nutritional Medicine (INUM) and Lübeck Institute of Dermatology (LIED), University of Lübeck (UzL) and University Medical Center Schleswig-Holstein (UKSH), Ratzeburger Allee 160, 23538 Lübeck, Germany; Department of Pharmacology, Faculty of Medicine, University of Latvia, Jelgavas iela 3, 1004 Riga, Latvia; Department of Neurobiology, School of Neuroscience, Biochemistry and Biophysics, The Georg S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv 6997801, Israel
Pahnke, Jens

Hypericum perforatum (St. John’s wort) has been described to be beneficial for the treatment of Alzheimer’s disease (AD). Different extractions have demonstrated efficiency in mice and humans, esp. extracts with a low hypericin and hyperforin content to reduce side effects such as phototoxicity. In order to systematically elucidate the therapeutic effects of H. perforatum extracts with different polarities, APP-transgenic mice were treated with a total ethanol extract (TE), a polar extract obtained from TE, and an apolar supercritical CO2 (scCO2) extract. The scCO2 extract was formulated with silicon dioxide (SiO2) for better oral application. APP-transgenic mice were treated with several extracts (total, polar, apolar) at different concentrations. We established an early treatment paradigm from the age of 40 days until the age of 80 days, starting before the onset of cerebral β-amyloid (Aβ) deposition at 45 days of age. Their effects on intracerebral soluble and insoluble Aβ were analyzed using biochemical analyses. Our study confirms that the scCO2 H. perforatum formulation shows better biological activity against Aβ-related pathological effects than the TE or polar extracts. Clinically, the treatment resulted in a dose-dependent improvement in food intake with augmentation of the body weight, and, biochemically, it resulted in a significant reduction in both soluble and insoluble Aβ (−27% and −25%, respectively). We therefore recommend apolar H. perforatum extracts for the early oral treatment of patients with mild cognitive impairment or early AD.

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