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Curculigoside (CCG) is a phenolic glycoside compound extracted from the root of a natural plant called Curculigo orchioides Gaertn. In this study, the neuroprotective effect of CCG through oxidative stress mediated mitochondrial dysfunction on L-glutamate (L-Glu)-damaged hippocampal neuron cell line (HT22) and APPswe/PSEN1dE9 transgenic (APP/PS1) mice were investigated. Observably, CCG in L-Glu-damaged HT22 cells suppressed apoptosis, reduced the accumulation of reactive oxygen species, balanced the mitochondrial membrane potential and prevented the over-influx of calcium. In APP/PS1 mice, 4-week CCG administration significantly improved their memory and behavioral impairments, enhanced the function of cholinergic system, reduced the deposition of Aβ and neurofibrillary fiber tangles caused by tau phosphorylation, and suppressed the development and progression of oxidative stress in brains of APP/PS1 mice. Based on the screening of proteomic analysis on hippocampus, CCG were confirmed that it could regulate the expression levels of proteins related to mitochondrial dysfunction, mainly through activating on AMPK/Nrf2 signaling, in APP/PS1 mice and L-Glu-exposed HT22 cells. CCG has a prominent neuroprotective effect on regulate the AMPK/Nrf2-mediated mitochondrial dysfunction in cells APP/PS1 mice support CCG is a potentially potent drug for AD treatment and merits further investigation.


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Neuroprotective effects of curculigoside against Alzheimer’s disease via regulation oxidative stress mediated mitochondrial dysfunction in L-Glu-exposed HT22 cells and APP/PS1 mice

Show Author's information Wenqi Wang1Yidi Qu1Siyu LiJinyu ChuHongxin YangLirong TengDi Wang( )
School of Life Sciences, Jilin University, Changchun 130012, China

1These authors contributed equally to this work.

Abstract

Curculigoside (CCG) is a phenolic glycoside compound extracted from the root of a natural plant called Curculigo orchioides Gaertn. In this study, the neuroprotective effect of CCG through oxidative stress mediated mitochondrial dysfunction on L-glutamate (L-Glu)-damaged hippocampal neuron cell line (HT22) and APPswe/PSEN1dE9 transgenic (APP/PS1) mice were investigated. Observably, CCG in L-Glu-damaged HT22 cells suppressed apoptosis, reduced the accumulation of reactive oxygen species, balanced the mitochondrial membrane potential and prevented the over-influx of calcium. In APP/PS1 mice, 4-week CCG administration significantly improved their memory and behavioral impairments, enhanced the function of cholinergic system, reduced the deposition of Aβ and neurofibrillary fiber tangles caused by tau phosphorylation, and suppressed the development and progression of oxidative stress in brains of APP/PS1 mice. Based on the screening of proteomic analysis on hippocampus, CCG were confirmed that it could regulate the expression levels of proteins related to mitochondrial dysfunction, mainly through activating on AMPK/Nrf2 signaling, in APP/PS1 mice and L-Glu-exposed HT22 cells. CCG has a prominent neuroprotective effect on regulate the AMPK/Nrf2-mediated mitochondrial dysfunction in cells APP/PS1 mice support CCG is a potentially potent drug for AD treatment and merits further investigation.

Keywords: Alzheimer's disease, Oxidative stress, Apoptosis, Mitochondrial dysfunction, Curculigoside, AMPK/Nrf2 signaling

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Received: 23 February 2021
Revised: 12 April 2021
Accepted: 05 June 2021
Published: 18 November 2022
Issue date: July 2023

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© 2023 Beijing Academy of Food Sciences. Publishing services by Elsevier B.V. on behalf of KeAi Communications Co., Ltd.

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Acknowledgements

This work was supported by the Science and Technology Develop Project in Jilin Province of China (20200201030JC), the Scientific Research Project of Education Department of Jilin Province in China (JJKH20211461KJ) and Characteristic Innovation Project for Guangdong University of China (2019KTSCX221).

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