Homoplantaginin Antagonizes -Methyl-d-aspartate Receptor and Extracellular Signal-Regulated Kinase Signaling in Aβ Oligomers-Induced Neuropathology/Toxicity.
Journal
Journal of agricultural and food chemistry
Journal Volume
72
Journal Issue
51
ISSN
1520-5118
Date Issued
2024-12-25
Author(s)
Chen, Ting-Yu
Chen, Yi-Ru
Hsu, Ming-Lung
Liao, Yueh-Ting
Wu, Chia-Hsuan
Yang, Wen-Chin
Lin, Wenwei
Lin, Yenshou
Abstract
Extracts from plants/herbals are great resources of drugs and nutrients. Baicalein, a component present in , was previously found to alleviate the abnormal depolarization brought about by Aβ oligomers. We extended this promising outcome by screening baicalein derivatives, and a natural compound named homoplantaginin was pinpointed. In this study, we aimed to investigate the effects of homoplantaginin on animal behavior and explore its neuronal functioning/mechanism. In behavior tests, impairments of novel object recognition and of spatial learning/memory were reversed by homoplantaginin in a J20 Alzheimer's disease (AD) mouse model. Utilizing primary glutamatergic neurons, homoplantaginin was found to prevent the Aβ oligomer-induced increase in ERK phosphorylation. Furthermore, homoplantaginin inhibits both AMPA-insult and NMDA-insult depolarization; this was assessed using DiBAC4(3), a membrane potential sensitive dye. Finally, homoplantaginin blocks both Aβ oligomer-induced and NMDA-induced calcium influx, which was assessed by intracellular calcium measurement using Fura2/AM. Interestingly, homoplantaginin immediately blunts the steady state calcium influx caused by NMDA. Taken together, homoplantaginin is capable of inhibiting Aβ oligomer-induced pathophysiology, in particular at the receptor level. This pure compound has great potential to be developed as a clinical therapeutic drug.
Subjects
Alzheimer’s disease
ERK
behavior tests
calcium influx
depolarization
homoplantaginin
Type
journal article