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

• Published in: International journal of molecular sciences 2024-01, Vol.25 (2), p.1301
• Main Authors: El Menuawy, Ahmed, Brüning, Thomas, Eiriz, Iván, Hähnel, Urs, Marthe, Frank, Möhle, Luisa, Górska, Anna Maria, Santos-García, Irene, Wangensteen, Helle, Wu, Jingyun, Pahnke, Jens
• Format: Article
• Language: English
• Subjects: Advertising executives; Alzheimer Disease - chemically induced; Alzheimer Disease - drug therapy; Alzheimer's disease; Amyloid beta-Peptides - toxicity; Animal cognition; Animals; Biological activity; Biomarkers; Body weight; Brain research; Carbon dioxide; Humans; Hypericum - chemistry; Hypericum perforatum; Infant; Manufacturing; MCI; Mice; Mice, Transgenic; Neurotoxicity; NMR; Nuclear magnetic resonance; Oral administration; Particle size; Phytotherapy; Plant Extracts - chemistry; Plant Extracts - pharmacology; Plant Extracts - therapeutic use; Proteins; silica gel; Silicon Dioxide - therapeutic use; St. John’s wort; Toxicity
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms25021301

(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 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 CO (scCO ) extract. The scCO extract was formulated with silicon dioxide (SiO ) 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 scCO 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 extracts for the early oral treatment of patients with mild cognitive impairment or early AD.