Donepezil provides neuroprotective effects against brain injury and Alzheimer's pathology under conditions of cardiac ischemia/reperfusion injury

Ongnok, Benjamin; Khuanjing, Thawatchai; Chunchai, Titikorn; Kerdphoo, Sasiwan; Jaiwongkam, Thidarat; Chattipakorn, Nipon

doi:10.1016/j.bbadis.2020.165975

Cited by 40 publications

(26 citation statements)

References 44 publications

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“…In the present study, DON managed to invert the overproduction of free radicals induced by scopolamine administration with a significant suppression effect on PCO and MDA production. It has been reported that Donepezil improves mitochondrial dynamics, ameliorates microglia activation, decreases the Aβ accumulation and finally modulates proinflammatory cytokines interleukin 16 and tumor necrosis factor ( Jiang et al., 2019 ; Ongnok et al., 2021 ). In addition to DON neuro-protective effects, donepezil managed to recover cellular antioxidant recourses to normal levels, and yet modulates GSH levels as an endogenous antioxidant.…”

Section: Discussionmentioning

confidence: 99%

Protective effects of Vinca herbaceous extract against scopolamine-induced behavioral disturbances and brain oxidative stress in rats

Hosseini

Mahmoudi

Eskandari

et al. 2022

Heliyon

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Section: Discussionmentioning

confidence: 99%

Protective effects of Vinca herbaceous extract against scopolamine-induced behavioral disturbances and brain oxidative stress in rats

Hosseini

Mahmoudi

Eskandari

et al. 2022

Heliyon

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“…Several studies have described the symptomatic effects of donepezil in animal models of dementia and AD, but few in vivo studies have evaluated donepezil neuroprotective effects regarding the disease‐modifying actions of this compound alone or in combination (Jiangbo & Liyun, 2018; Krishna et al, 2020; Ongnok et al, 2021; Yang et al, 2020). Here, we studied the effect of chronic low doses of an I 2 ligand, donepezil and their combination.…”

Section: Discussionmentioning

confidence: 99%

Disease‐modifying treatment with I₂ imidazoline receptor ligand LSL60101 in an Alzheimer's disease mouse model: a comparative study with donepezil

Vasilopoulou

Rodríguez-Arévalo

Bagán

et al. 2021

British J Pharmacology

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Background and Purpose: The development of effective therapeutic strategies against Alzheimer's disease (AD) remains a challenge. I 2 imidazoline receptor ligands have a neuroprotective role in AD. Moreover, co-treatment of AChE inhibitors with neuroprotective agents have shown better effects on the prevention of dementia.Here, we assessed the potential therapeutic effect of the I 2 ligand, donepezil and their combination in 5XFAD mice. Experimental Approach: 5XFAD female mice were treated with low doses (1 mgÁkg À1 Áday À1 ) of LSL60101, donepezil and donepezil plus LSL60101, during 4 weeks per os. Novel object recognition, Morris water maze, open field, elevated plus maze and three-chamber tests were used to evaluate the cognitive and behavioural status after treatment. The effects on AD-like pathology were assessed with immunohistochemistry, western blot, ELISA and qPCR. Key Results: Chronic low-dose treatment with LSL60101 and donepezil reversed cognitive deficits and impaired social behaviour. LSL60101 treatment did not affect anxiety-like behaviour in contrast to donepezil. In the 5XFAD brains, LSL60101 and donepezil/LSL60101 treatments attenuated amyloid-β pathology by decreasing amyloid-β 40 and amyloid-β 42 levels, amyloid-β plaque number and tau hyperphosphorylation. These alterations were accompanied by reduced microglia marker Iba-1 levels and increased Trem2 gene expression. LSL60101 and donepezil decreased glial fibrillary acidic protein (GFAP) astrocytic marker reactivity. However, only LSL60101 and donepezil/LSL60101 treatments significantly increased the synaptic marker levels of post-synaptic density protein 95 and synaptophysin. Conclusion and Implications:Chronic low-dose treatment with selective I 2 -ligands can be an effective treatment for AD and provide insights into combination treatments for symptomatic and disease-modifying drugs.

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“…Several studies have described the symptomatic effects of donepezil in animal models of dementia and AD, but few in vivo studies have evaluated donepezil neuroprotective effects regarding the disease-modifying actions of this compound alone or in combination (Jiangbo and Liyun, 2018;Krishna et al, 2020;Yang et al, 2020;Ongnok et al, 2021). Here, we studied the effect of chronic low doses of an I2IR ligand, donepezil and their combination.…”

Section: Discussionmentioning

confidence: 99%

Disease-modifying treatment with I2 imidazoline receptor ligand LSL60101 in an Alzheimer’s disease mouse model : A Comparative study with donepezil

Vasilopoulou

Rodríguez-Arévalo

Bagán

et al. 2020

Preprint

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Background and Purpose: The development of effective therapeutic strategies against Alzheimer’s disease (AD) remains a challenge. I2 Imidazoline receptors (I2-IR) ligands have a neuroprotective role in AD. While co-treatment of acetylcholinesterase inhibitors with neuroprotective agents have shown better effects on the prevention of dementia. Here, we assessed the potential therapeutic effect of the I2-IR ligand LSL60101, donepezil and their combination in 5XFAD mice. Experimental Approach: 5XFAD female mice were treated with low doses of LSL60101 (1mg/kg/day), donepezil (1mg/kg/day), and donepezil plus LSL60101 (1+1mg/kg/day), during 4 weeks per os. Novel object recognition, Morris water maze, open field, elevated plus maze and three-chamber tests were employed to evaluate the cognitive and behavioural status of the mice after treatment. The effects of the treatments on AD-like pathology were assessed with immunohistochemistry, Western blot and qPCR. Key results: Chronic low-dose treatment with LSL60101 and donepezil reversed cognitive deficits and impaired social behaviour. LSL60101 treatment did not affect anxiety-like behaviour in contrast to donepezil. In the 5XFAD brains, LSL60101 and donepezil/LSL60101 treatments decreased Aβ-pathology and Tau hyperphosphorylation, and these alterations were accompanied by decreased microglia marker Iba-1 levels and increased Trem2 gene expression. LSL60601 and donepezil decreased glial fibrillary acidic protein (GFAP) astrocytic marker reactivity. However, only LSL60601 treatment significantly increased the levels of the synaptic markers post-density 95 (PSD95) and synaptophysin (SYN). Conclusion and implications: Our results suggest that chronic low dose treatment with selective I2-IR ligands can be an effective treatment for AD and provide insights into combination treatments of symptomatic and disease-modifying drugs

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Donepezil provides neuroprotective effects against brain injury and Alzheimer's pathology under conditions of cardiac ischemia/reperfusion injury

Cited by 40 publications

References 44 publications

Protective effects of Vinca herbaceous extract against scopolamine-induced behavioral disturbances and brain oxidative stress in rats

Protective effects of Vinca herbaceous extract against scopolamine-induced behavioral disturbances and brain oxidative stress in rats

Disease‐modifying treatment with I₂ imidazoline receptor ligand LSL60101 in an Alzheimer's disease mouse model: a comparative study with donepezil

Disease-modifying treatment with I2 imidazoline receptor ligand LSL60101 in an Alzheimer’s disease mouse model : A Comparative study with donepezil

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Donepezil provides neuroprotective effects against brain injury and Alzheimer's pathology under conditions of cardiac ischemia/reperfusion injury

Cited by 40 publications

References 44 publications

Protective effects of Vinca herbaceous extract against scopolamine-induced behavioral disturbances and brain oxidative stress in rats

Protective effects of Vinca herbaceous extract against scopolamine-induced behavioral disturbances and brain oxidative stress in rats

Disease‐modifying treatment with I2 imidazoline receptor ligand LSL60101 in an Alzheimer's disease mouse model: a comparative study with donepezil

Disease-modifying treatment with I2 imidazoline receptor ligand LSL60101 in an Alzheimer’s disease mouse model : A Comparative study with donepezil

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Disease‐modifying treatment with I₂ imidazoline receptor ligand LSL60101 in an Alzheimer's disease mouse model: a comparative study with donepezil