ReferenceID 6350
Identification of a novel BACE1 inhibitor, timosaponin A-III, for treatment of Alzheimer's disease by a cell extraction and chemogenomics target knowledgebase-guided method
Phytomedicine
BACKGROUND: Rhizoma Anemarrhenae (RA) has been conventionally used for treatment of Alzheimer's disease (AD) in Traditional Chinese Medicine, and thus, the active components from RA can be screened. PURPOSE: This researc
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Record Fields
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- Reference Id
- 6350
- Evidence Id
- 22940
- Core Evidence Id
- 22940
- Source Reference Id
- 5980
- Herb2 Reference Id
- HBREF006777
- Subject Paper Key
- HBIN046440_32502824
- Pubmed Id
- 32502824
- Doi
- 10.1016/j.phymed.2020.153244
- Paper Title
- Identification of a novel BACE1 inhibitor, timosaponin A-III, for treatment of Alzheimer's disease by a cell extraction and chemogenomics target knowledgebase-guided method
- Paper Abstract
- BACKGROUND: Rhizoma Anemarrhenae (RA) has been conventionally used for treatment of Alzheimer's disease (AD) in Traditional Chinese Medicine, and thus, the active components from RA can be screened. PURPOSE: This research aimed to identify the active components of RA and their targets and further clarify the molecular mechanisms underlying its anti-AD activity. METHODS: First, the potential active compounds from RA were screened by neurocyte extraction and micro-dialysis methods. Second, the potential targets were predicted by a chemogenomics target knowledgebase and further explored by surface plasmon resonance and enzyme activity assays. Third, the pharmacological effects were evaluated by employing APP/PS1 transgenic mice and SH-SY5Y-APP cells. ELISAs and Western blot analyses were used to evaluate the expression of key molecules in the amyloidogenic and NMDAR/ERK pathways. RESULTS: Timosaponin A-III (TA-III) was screened and identified as a potential active component for the anti-AD activity, and BACE1 was proven to be a potential high-affinity target. Enzyme kinetic analysis showed that TA-III had strong noncompetitive inhibitory activity against BACE1. The in vitro and in vivo assays indicated that TA-III had pharmacological effects through improving memory impairment, reducing Abeta aggregation via the amyloidogenic pathway and preventing neuronal impairment through downregulating the NMDAR/ERK signaling pathway. CONCLUSION: TA-III targets BACE1 to reduce Abeta aggregation through down-regulating the NMDAR/ERK pathway for treating AD.
- Journal
- Phytomedicine
- Publish Year
- 2020
- Experiment Subject
- mouse; sh-sy5y-app cells
- Experiment Type
- Animal & Cell Experiment
- Phenotype Related
- Neuronal Impairment; Alzheimer's Disease
- Paper Title Cn
- Paper Title En
- Identification of a novel BACE1 inhibitor, timosaponin A-III, for treatment of Alzheimer's disease by a cell extraction and chemogenomics target knowledgebase-guided method
- Bilingual Status
- semi_complete