Dengzhan Shengmai capsules and their active component scutellarin prevent cognitive decline in APP/PS1 mice by accelerating A beta aggregation and reducing oligomers formation
单位：[1]Peking University China-Japan Friendship School of Clinical Medicine, Beijing, 100029, China[2]Department of Neurology, China-Japan Friendship Hospital, 2 Yinghuayuan East Street, Chaoyang District, Beijing 100029, China[3]State Key Laboratory of Cognitive Neuroscience and Learning and IDG/McGovern Institute for Brain Research, Beijing Normal University, Beijing 100875, China[4]BABRI Centre, Beijing Normal University, Beijing 100875, China[5]Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing 100700, China[6]Beijing Key Laboratory of Gene Resource and Molecular Development, College of Life Sciences, Beijing Normal University, 100875 Beijing, China[7]College of Chemistry, Beijing Normal University, Beijing, China
There is currently no effective treatment to prevent the progress of Alzheimer's disease (AD). The traditional Chinese herbs Dengzhan Shengmai (DZSM) capsules and their active component scutellarin possess multiple effects and are clinically used for the treatment of cerebrovascular diseases. Scutellarin has been reported to affect A beta aggregation. However, the effects of DZSM capsules on AD remain unknown. Through in vivo experiments, our study proved that the alleviating effects of DZSM capsules on cognitive deficits of AD mice were due to the role of scutellarin, which up-regulated low toxic amyloid plaques and down-regulated highly toxic soluble A beta 42 and A beta 40 levels in cortex. In vitro, we confirmed scutellarin's role in accelerating transforming A beta 42 monomers into high-molecular-mass aggregates by biochemical assays, which supported the results observed in drug-treated APP/PS1 mice. In detail, the 1:10 ratio of scutellarin/A beta 42 mixtures promoted production of large beta-sheet-rich fibrils whereas the 1:1 ratio promoted production of protofibrils. In addition, the binding between scutellarin and A beta monomers was quantified by microscale thermophoresis test and the apparent dissociation constant (Kd) was 1284.4 +/- 238.8 mu M. What's more, binding regions between scutellarin and A beta fibrils were predicted by computational docking models and scutellarin might bind parallel to the long axis of A beta 42 fibrils targeting hydrophobic grooves at residues 35-36 or 39. In conclusion, DZSM capsules protected against cognitive defects of AD through scutellarin-mediated acceleration of A beta aggregation into fibrils or protofibrils and reduction of soluble A beta oligomers, thus suggesting potential clinical applications of DZSM capsules and scutellarin in the treatment of AD.
基金：
National Key R&D Program of China [2016YFC1306301]; State Key Program of National Natural Science of ChinaNational Natural Science Foundation of China (NSFC) [81430100]; Beijing Municipal Science & Technology CommissionBeijing Municipal Science & Technology Commission [Z161100000216135]; National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [31700997]; China National Funds for Distinguished Young ScientistsNational Natural Science Foundation of China (NSFC) [81625025]
语种：
外文
被引次数：
WOS：
中科院(CAS)分区：
出版当年[2019]版：
大类|3 区医学
小类|3 区医学：研究与实验3 区药学
最新[2025]版：
大类|2 区医学
小类|2 区医学：研究与实验2 区药学
JCR分区：
出版当年[2018]版：
Q1PHARMACOLOGY & PHARMACYQ2MEDICINE, RESEARCH & EXPERIMENTAL
最新[2023]版：
Q1MEDICINE, RESEARCH & EXPERIMENTALQ1PHARMACOLOGY & PHARMACY
第一作者单位：[1]Peking University China-Japan Friendship School of Clinical Medicine, Beijing, 100029, China
通讯作者：
通讯机构：[1]Peking University China-Japan Friendship School of Clinical Medicine, Beijing, 100029, China[2]Department of Neurology, China-Japan Friendship Hospital, 2 Yinghuayuan East Street, Chaoyang District, Beijing 100029, China[3]State Key Laboratory of Cognitive Neuroscience and Learning and IDG/McGovern Institute for Brain Research, Beijing Normal University, Beijing 100875, China[*1]Peking University China-Japan Friendship School of Clinical Medicine, Beijing, 100029, China[*2]Department of Neurology, China-Japan Friendship Hospital, 2 Yinghuayuan East Street, Chaoyang District, Beijing 100029, China.[*3]State Key Laboratory of Cognitive Neuroscience and Learning and IDG/McGovern Institute for Brain Research, Beijing Normal University, Beijing 100875, China
推荐引用方式(GB/T 7714)：
Zhang Shujuan,Zhang Jianxiang,Wei Dongfeng,et al.Dengzhan Shengmai capsules and their active component scutellarin prevent cognitive decline in APP/PS1 mice by accelerating A beta aggregation and reducing oligomers formation[J].BIOMEDICINE & PHARMACOTHERAPY.2020,121:doi:10.1016/j.biopha.2019.109682.
APA：
Zhang, Shujuan,Zhang, Jianxiang,Wei, Dongfeng,An, Haiting,Liu, Wei...&Zhang, Zhanjun.(2020).Dengzhan Shengmai capsules and their active component scutellarin prevent cognitive decline in APP/PS1 mice by accelerating A beta aggregation and reducing oligomers formation.BIOMEDICINE & PHARMACOTHERAPY,121,
MLA：
Zhang, Shujuan,et al."Dengzhan Shengmai capsules and their active component scutellarin prevent cognitive decline in APP/PS1 mice by accelerating A beta aggregation and reducing oligomers formation".BIOMEDICINE & PHARMACOTHERAPY 121.(2020)
