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

ABSTRACT: Alzheimer's disease (AD) is a neurodegenerative disease characterized by neuronal loss, cognitive impairment, and aphasia. Aggregation of ?-amyloid (A?) 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 A? 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 A?-peptide aggregation in the hippocampus and reduced cognitive deficits in 5×FAD 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 A? generation by modulating BACE1 activity via the GSK3?/NF-?B pathway in HEK293-APPsw cells. These findings showed that EPOS reduced cognitive deficits in an AD model via modulation of the A? peptide aggregation pathway.

SUBMITTER: Yan L 

PROVIDER: S-EPMC7456918 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature