Hyperoside protects the blood-brain barrier from neurotoxicity of amyloid beta 1–42
| Autor: | Li-Mi Zhang, Xiao-Hui Liu, Chenyang Liu, Guran Yu, Kuan Bai |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
amyloid beta 1–42 Amyloid beta bEnd.3 cells1 Hyperoside anti-apoptosis Pharmacology Blood–brain barrier Occludin 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Developmental Neuroscience medicine Viability assay nerve regeneration biology Chemistry Cytochrome c Neurotoxicity Alzheimer's disease blood-brain barrier medicine.disease 030104 developmental biology medicine.anatomical_structure Apoptosis tight junction proteins biology.protein neural regeneration 030217 neurology & neurosurgery hyperoside Research Article |
| Zdroj: | Neural Regeneration Research |
| ISSN: | 1876-7958 1673-5374 |
| Popis: | Mounting evidence indicates that amyloid β protein (Aβ) exerts neurotoxicity by disrupting the blood-brain barrier (BBB) in Alzheimer's disease. Hyperoside has neuroprotective effects both in vitro and in vivo against Aβ. Our previous study found that hyperoside suppressed Aβ1-42-induced leakage of the BBB, however, the mechanism remains unclear. In this study, bEnd.3 cells were pretreated with 50, 200, or 500 µM hyperoside for 2 hours, and then exposed to Aβ1-42 for 24 hours. Cell viability was determined using 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide assay. Flow cytometry and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assay were used to analyze cell apoptosis. Western blot assay was carried out to analyze expression levels of Bax, Bcl-2, cytochrome c, caspase-3, caspse-8, caspase-9, caspase-12, occludin, claudin-5, zonula occludens-1, matrix metalloproteinase-2 (MMP-2), and MMP-9. Exposure to Aβ1-42 alone remarkably induced bEnd.3 cell apoptosis; increased ratios of cleaved caspase-9/caspase-9, Bax/Bcl-2, cleaved caspase-8/caspase-8, and cleaved caspase-12/caspase-12; increased expression of cytochrome c and activity of caspase-3; diminished levels of zonula occludens-1, claudin-5, and occludin; and increased levels of MMP-2 and MMP-9. However, hyperoside pretreatment reversed these changes in a dose-dependent manner. Our findings confirm that hyperoside alleviates fibrillar Aβ1-42-induced BBB disruption, thus offering a feasible therapeutic application in Alzheimer's disease. |
| Databáze: | OpenAIRE |
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