ReferenceID 624

Modulation of the Aβ-Peptide-Aggregation Pathway by Active Compounds From Platycladus orientalis Seed Extract in Alzheimer's Disease Models

Front Aging Neurosci

Alzheimer's disease (AD) is a neurodegenerative disease characterized by neuronal loss, cognitive impairment, and aphasia. Aggregation of beta-amyloid (Abeta) peptide in the brain is considered a key mechanism in the dev

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Reference Id
624
Evidence Id
17214
Core Evidence Id
17214
Source Reference Id
1240
Herb2 Reference Id
HBREF002037
Subject Paper Key
HERB000615_32922281
Pubmed Id
32922281
Doi
10.3389/fnagi.2020.00207
Paper Title
Modulation of the Aβ-Peptide-Aggregation Pathway by Active Compounds From Platycladus orientalis Seed Extract in Alzheimer's Disease Models
Paper Abstract
Alzheimer's disease (AD) is a neurodegenerative disease characterized by neuronal loss, cognitive impairment, and aphasia. Aggregation of beta-amyloid (Abeta) peptide in the brain is considered a key mechanism in the development of AD. In the past 20 years, many compounds have been developed to inhibit Abeta aggregation and accelerate its degradation. Platycladus orientalis seed is a traditional Chinese medicine used to enhance intelligence and slow aging. We previously found that Platycladus orientalis seed extract (EPOS) inhibited Abeta-peptide aggregation in the hippocampus and reduced cognitive deficits in 5xFAD mice. However, the mechanisms of these effects have not been characterized. To characterize the protective mechanisms of EPOS, we used a transgenic Caenorhabditis elegans CL4176 model to perform Bioactivity-guided identification of active compounds. Four active compounds, comprising communic acid, isocupressic acid, imbricatolic acid, and pinusolide, were identified using 13C-and 1H-NMR spectroscopy. Furthermore, we showed that isocupressic acid inhibited Abeta generation by modulating BACE1 activity via the GSK3beta/NF-kappaB pathway in HEK293-APPsw cells. These findings showed that EPOS reduced cognitive deficits in an AD model via modulation of the Abeta peptide aggregation pathway.
Journal
Front Aging Neurosci
Publish Year
2020
Experiment Subject
mouse; hek293-appsw cells
Experiment Type
Animal Experiment
Phenotype Related
Alzheimer's Disease; Cognitive Impairment; Neuronal Loss; Aphasia; Neurodegenerative Disease; Cognitive Deficits; 5xfad
Paper Title Cn
Paper Title En
Modulation of the Aβ-Peptide-Aggregation Pathway by Active Compounds From Platycladus orientalis Seed Extract in Alzheimer's Disease Models
Bilingual Status
semi_complete