Hyperoside protects the blood-brain barrier from neurotoxicity of amyloid beta 1–42

作     者：Chen-Yang Liu Kuan Bai Xiao-Hui Liu Li-Mi Zhang Gu-Ran Yu 

作者机构：Department of Neurology Jiangsu Traditional Chinese Medicine Hospital the Affiliated Hospital of Nanjing University of Traditional Chinese Medicine Nanjing Jiangsu Province China Graduate School of Nanjing University of Traditional Chinese Medicine Nanjing Jiangsu Province China 

出 版 物：《Neural Regeneration Research》 (中国神经再生研究（英文版）)

年 卷 期：2018年第13卷第11期

页      面：1974-1980页

核心收录：

学科分类：0710[理学-生物学] 1008[医学-中药学(可授医学、理学学位)] 1006[医学-中西医结合] 1002[医学-临床医学] 1001[医学-基础医学(可授医学、理学学位)] 100602[医学-中西医结合临床] 10[医学] 

基　　金：financially supported by the National Natural Science Foundation of China,No.81573771 the Natural Science Foundation of Jiangsu Province of China,No.BK20151599 

主　　题：nerve regeneration Alzheimer's disease amyloid beta 1-42 blood-brain barrier bEnd.3 cells tight junction proteins hyperoside anti-apoptosis neural regeneration 

摘      要：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 d UTP 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, cleav ed 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.