2. Academic Validation
  3. Dengzhan Shengmai capsules and their active component scutellarin prevent cognitive decline in APP/PS1 mice by accelerating Aβ aggregation and reducing oligomers formation

Dengzhan Shengmai capsules and their active component scutellarin prevent cognitive decline in APP/PS1 mice by accelerating Aβ aggregation and reducing oligomers formation

  • Biomed Pharmacother. 2020 Jan;121:109682. doi: 10.1016/j.biopha.2019.109682.
Shujuan Zhang 1,  Jianxiang Zhang 2,  Dongfeng Wei 3,  Haiting An 4,  Wei Liu 5,  Yihui Lai 2,  Te Yang 2,  Wen Shao 1,  Yaping Huang 1,  Lei Wang 1,  Fei Dou 2,  Dantao Peng 6,  Zhanjun Zhang 7
Affiliations

Affiliations

  • 1 Peking University China-Japan Friendship School of Clinical Medicine, Beijing, 100029, China; Department of Neurology, China-Japan Friendship Hospital, 2 Yinghuayuan East Street, Chaoyang District, Beijing 100029, China.
  • 2 Beijing Key Laboratory of Gene Resource and Molecular Development, College of Life Sciences, Beijing Normal University, 100875 Beijing, China.
  • 3 BABRI Centre, Beijing Normal University, Beijing 100875, China; Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing 100700, China.
  • 4 State Key Laboratory of Cognitive Neuroscience and Learning and IDG/McGovern Institute for Brain Research, Beijing Normal University, Beijing 100875, China; BABRI Centre, Beijing Normal University, Beijing 100875, China.
  • 5 College of Chemistry, Beijing Normal University, Beijing, China.
  • 6 Peking University China-Japan Friendship School of Clinical Medicine, Beijing, 100029, China; Department of Neurology, China-Japan Friendship Hospital, 2 Yinghuayuan East Street, Chaoyang District, Beijing 100029, China. Electronic address: [email protected].
  • 7 State Key Laboratory of Cognitive Neuroscience and Learning and IDG/McGovern Institute for Brain Research, Beijing Normal University, Beijing 100875, China; BABRI Centre, Beijing Normal University, Beijing 100875, China. Electronic address: [email protected].
PMID: 31810113 DOI: 10.1016/j.biopha.2019.109682
Abstract

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 Aβ 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 Aβ42 and Aβ40 levels in cortex. In vitro, we confirmed scutellarin's role in accelerating transforming Aβ42 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/Aβ42 mixtures promoted production of large β-sheet-rich fibrils whereas the 1:1 ratio promoted production of protofibrils. In addition, the binding between scutellarin and Aβ monomers was quantified by microscale thermophoresis test and the apparent dissociation constant (Kd) was 1284.4 ± 238.8 μM. What's more, binding regions between scutellarin and Aβ fibrils were predicted by computational docking models and scutellarin might bind parallel to the long axis of Aβ42 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 Aβ aggregation into fibrils or protofibrils and reduction of soluble Aβ oligomers, thus suggesting potential clinical applications of DZSM capsules and scutellarin in the treatment of AD.

Keywords

Alzheimer’s disease; Aβ aggregation; DZSM capsules; Fibrils; Scutellarin.

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