Mori Fructus improves cognitive and neuronal dysfunction induced by beta-amyloid toxicity through the GSK-3β pathway in vitro and in vivo
| Autor: | Myung Sook Oh, Mi Kyeong Lee, Min Seo Kang, Hanbyeol Park, Soonmin Lim, Jin Gyu Choi, Hyun Uk Jeong, Hyo Geun Kim, Gunhyuk Park |
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| Rok vydání: | 2015 |
| Předmět: |
Male
medicine.medical_specialty Amyloid beta Apoptosis tau Proteins Pharmacology Hippocampus Neuroprotection Rats Sprague-Dawley Glycogen Synthase Kinase 3 Alzheimer Disease GSK-3 Internal medicine Drug Discovery medicine Animals Protein kinase B GSK3B Membrane Potential Mitochondrial Neurons Mice Inbred ICR Amyloid beta-Peptides Glycogen Synthase Kinase 3 beta Cell Death biology Caspase 3 Plant Extracts business.industry Neurodegeneration medicine.disease Peptide Fragments Rats Disease Models Animal Neuroprotective Agents Endocrinology Fruit biology.protein Morus Alzheimer's disease business Phytotherapy |
| Zdroj: | Journal of Ethnopharmacology. 171:196-204 |
| ISSN: | 0378-8741 |
| DOI: | 10.1016/j.jep.2015.05.054 |
| Popis: | Ethnopharmacological relevance A growing body of literature supports the concept that antiaging herbs may be potential candidates for use in treating age-related neurodegeneration, including Alzheimer׳s disease (AD). Mori Fructus is a well-known traditional herbal medicine, food, and dietary supplement. This study employed models of amyloid beta (Aβ)-induced AD to investigate the protective effects of Mori Fructus ethanol extract (ME) against age-related disease and cognitive deficits. Materials and methods To examine the protective effect of ME, we measured cell viability, cytotoxicity, and survival in rat primary hippocampal cultures. We performed behavioral tests and histological analysis in mouse models of AD induced by Aβ25–35 toxicity. To investigate the mechanism underlying the protective effect, we performed western blotting using antibodies against apoptotic markers as well as the nonphosphorylated and phosphorylated forms of Akt, glycogen synthase kinase-3β (GSK-3β), and tau. We also measured apoptotic marker fluorescence intensity. Results ME significantly attenuated Aβ-induced cell damage, enhanced Akt and GSK-3β phosphorylation, and reduced tau phosphorylation. ME reduced apoptotic markers that were activated by GSK-3β, and reduced reactive oxygen species production. Further, ME decreased the B-cell lymphoma 2 (Bcl-2)/Bcl-2-associated X expression ratio, mitochondria depolarization, cytochrome c release from mitochondria, and caspase-3 activation. We confirmed that ME treatment improved cognitive impairment and neuronal cell death induced by Aβ25–35 toxicity in the mouse hippocampus via its antiapoptotic activity. Conclusions These results indicate that ME protects cognition and neurons in AD-like models induced by Aβ via reduction of tau phosphorylation and apoptosis through GSK-3β inactivation. |
| Databáze: | OpenAIRE |
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