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Cornuside Is a Potential Agent against Alzheimer's Disease via Orchestration of Reactive Astrocytes.

Authors :
Shi JZ
Zheng XM
Zhou YF
Yun LY
Luo DM
Hao JJ
Liu PF
Zhang WK
Xu JK
Yan Y
Xie XM
He YY
Pang XB
Source :
Nutrients [Nutrients] 2022 Aug 03; Vol. 14 (15). Date of Electronic Publication: 2022 Aug 03.
Publication Year :
2022

Abstract

Cornuside is an iridoid glycoside from Cornus officinalis , with the activities of anti-inflammatory, antioxidant, anti-mitochondrial dysfunction, and neuroprotection. In the present research, a triple-transgenic mice model of AD (3 × Tg-AD) was used to explore the beneficial actions and potential mechanism of cornuside on the memory deficits. We found that cornuside prominently alleviated neuronal injuries, reduced amyloid plaque pathology, inhibited Tau phosphorylation, and repaired synaptic damage. Additionally, cornuside lowered the release of interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and nitric oxide (NO), lowered the level of malondialdehyde (MDA), and increased the activity of superoxide dismutase (SOD) and the level of glutathione peroxidase (GSH-Px). Cornuside also significantly reduced the activation of astrocytes and modulated A1/A2 phenotypes by the AKT/Nrf2/NF-κB signaling pathway. We further confirmed that LY294002 and Nrf2 silencing could block the cornuside-mediated phenotypic switch of C6 cells induced by microglia conditioned medium (MCM) in response to lipopolysaccharide (LPS), which indicated that the effects of cornuside in astrocyte activation are dependent on AKT/Nrf2/NF-κB signaling. In conclusion, cornuside may regulate the phenotypic conversion of astrocytes, inhibit neuroinflammation and oxidative stress, improve synaptic plasticity, and alleviate cognitive impairment in mice through the AKT/Nrf2/NF-κB axis. Our present work provides an experimental foundation for further research and development of cornuside as a candidate drug for AD management.

Details

Language :
English
ISSN :
2072-6643
Volume :
14
Issue :
15
Database :
MEDLINE
Journal :
Nutrients
Publication Type :
Academic Journal
Accession number :
35956355
Full Text :
https://doi.org/10.3390/nu14153179