Celastrol attenuates Alzheimer’s disease-mediated learning and memory impairment by inhibiting endoplasmic reticulum stress-induced inflammation and oxidative stress

Introduction Alzheimer’s disease (AD) is triggered by biological mechanisms such as neuroinflammation and oxidative stress. Endoplasmic reticulum (ER) stress can lead to the expression of molecular chaperones in the ER, which helps in restoring cellular homeostasis. Researchers have highlighted the...

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Main Authors: Fanfan Cao, Limin Xu, Xiaoxue He, Yongbin Chi, Ying Wang, Qiuyun Liu, Denghai Zhang
Format: Article
Language:English
Published: Termedia Publishing House 2024-06-01
Series:Archives of Medical Science
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Online Access:https://www.archivesofmedicalscience.com/Celastrol-attenuates-Alzheimer-s-disease-mediated-learning-and-memory-impairment,189906,0,2.html
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author Fanfan Cao
Limin Xu
Xiaoxue He
Yongbin Chi
Ying Wang
Qiuyun Liu
Denghai Zhang
author_facet Fanfan Cao
Limin Xu
Xiaoxue He
Yongbin Chi
Ying Wang
Qiuyun Liu
Denghai Zhang
author_sort Fanfan Cao
collection DOAJ
description Introduction Alzheimer’s disease (AD) is triggered by biological mechanisms such as neuroinflammation and oxidative stress. Endoplasmic reticulum (ER) stress can lead to the expression of molecular chaperones in the ER, which helps in restoring cellular homeostasis. Researchers have highlighted the role of ER stress in the progression of AD, suggesting that regulating it could be a potential treatment strategy for AD. Material and methods We induced AD in mice by injecting amyloid beta-peptide 25-35 (Aβ25-35) bilaterally into the CA1 of the dorsal hippocampus. Some mice were administered celastrol intraperitoneally before the Aβ25-35 injection, while others received it after the injection. The mice underwent the Barnes maze cognitive test and Morris water maze test to assess learning and memory impairment. Levels of interleukin (IL)-1β, tumor necrosis factor α, and IL-10 were measured to evaluate inflammation, while total antioxidant capacity, catalase, malondialdehyde, and superoxide dismutase levels were analyzed to estimate oxidative stress. Results Our study showed that pre-treatment with celastrol could prevent learning and memory decline in AD mice by reducing inflammation and oxidative stress. Celastrol also inhibited AD-induced inflammation and oxidative stress. Additionally, celastrol suppressed AD progression by targeting ER stress. These results suggest that celastrol treatment could be beneficial in addressing learning and memory deficits in AD, paving the way for potential neuroprotective treatments. Conclusions Celastrol effectively improved learning and memory impairments in AD mice by targeting ER stress-induced inflammation and oxidative stress. This highlights the potential of celastrol as a therapeutic agent for AD.
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spelling doaj-art-d083dff76b004a27afa3e633e7ac7cc52025-08-20T03:49:32ZengTermedia Publishing HouseArchives of Medical Science1734-19221896-91512024-06-0121253855410.5114/aoms/189906189906Celastrol attenuates Alzheimer’s disease-mediated learning and memory impairment by inhibiting endoplasmic reticulum stress-induced inflammation and oxidative stressFanfan Cao0Limin Xu1Xiaoxue He2Yongbin Chi3Ying Wang4Qiuyun Liu5Denghai Zhang6School of Gongli Hospital Medical Technology, University of Shanghai for Science and Technology, Shanghai, ChinaDepartment of Clinical Laboratory, Gongli Hospital of Shanghai Pudong New Area, Shanghai, ChinaDepartment of Clinical Laboratory, Gongli Hospital of Shanghai Pudong New Area, Shanghai, ChinaShanghai Health Commission Key Lab of Artificial Intelligence (AI)-Based Management of Inflammation and Chronic Diseases, Department of Central Laboratory, Gongli Hospital of Shanghai Pudong New Area, Shanghai, ChinaShanghai Health Commission Key Lab of Artificial Intelligence (AI)-Based Management of Inflammation and Chronic Diseases, Department of Central Laboratory, Gongli Hospital of Shanghai Pudong New Area, Shanghai, ChinaDepartment of Ultrasound, Gongli Hospital of Shanghai Pudong New Area, Shanghai, ChinaShanghai Health Commission Key Lab of Artificial Intelligence (AI)-Based Management of Inflammation and Chronic Diseases, Department of Central Laboratory, Gongli Hospital of Shanghai Pudong New Area, Shanghai, ChinaIntroduction Alzheimer’s disease (AD) is triggered by biological mechanisms such as neuroinflammation and oxidative stress. Endoplasmic reticulum (ER) stress can lead to the expression of molecular chaperones in the ER, which helps in restoring cellular homeostasis. Researchers have highlighted the role of ER stress in the progression of AD, suggesting that regulating it could be a potential treatment strategy for AD. Material and methods We induced AD in mice by injecting amyloid beta-peptide 25-35 (Aβ25-35) bilaterally into the CA1 of the dorsal hippocampus. Some mice were administered celastrol intraperitoneally before the Aβ25-35 injection, while others received it after the injection. The mice underwent the Barnes maze cognitive test and Morris water maze test to assess learning and memory impairment. Levels of interleukin (IL)-1β, tumor necrosis factor α, and IL-10 were measured to evaluate inflammation, while total antioxidant capacity, catalase, malondialdehyde, and superoxide dismutase levels were analyzed to estimate oxidative stress. Results Our study showed that pre-treatment with celastrol could prevent learning and memory decline in AD mice by reducing inflammation and oxidative stress. Celastrol also inhibited AD-induced inflammation and oxidative stress. Additionally, celastrol suppressed AD progression by targeting ER stress. These results suggest that celastrol treatment could be beneficial in addressing learning and memory deficits in AD, paving the way for potential neuroprotective treatments. Conclusions Celastrol effectively improved learning and memory impairments in AD mice by targeting ER stress-induced inflammation and oxidative stress. This highlights the potential of celastrol as a therapeutic agent for AD.https://www.archivesofmedicalscience.com/Celastrol-attenuates-Alzheimer-s-disease-mediated-learning-and-memory-impairment,189906,0,2.htmlalzheimer’s diseasecelastrolendoplasmic reticulum stressinflammationoxidative stress
spellingShingle Fanfan Cao
Limin Xu
Xiaoxue He
Yongbin Chi
Ying Wang
Qiuyun Liu
Denghai Zhang
Celastrol attenuates Alzheimer’s disease-mediated learning and memory impairment by inhibiting endoplasmic reticulum stress-induced inflammation and oxidative stress
Archives of Medical Science
alzheimer’s disease
celastrol
endoplasmic reticulum stress
inflammation
oxidative stress
title Celastrol attenuates Alzheimer’s disease-mediated learning and memory impairment by inhibiting endoplasmic reticulum stress-induced inflammation and oxidative stress
title_full Celastrol attenuates Alzheimer’s disease-mediated learning and memory impairment by inhibiting endoplasmic reticulum stress-induced inflammation and oxidative stress
title_fullStr Celastrol attenuates Alzheimer’s disease-mediated learning and memory impairment by inhibiting endoplasmic reticulum stress-induced inflammation and oxidative stress
title_full_unstemmed Celastrol attenuates Alzheimer’s disease-mediated learning and memory impairment by inhibiting endoplasmic reticulum stress-induced inflammation and oxidative stress
title_short Celastrol attenuates Alzheimer’s disease-mediated learning and memory impairment by inhibiting endoplasmic reticulum stress-induced inflammation and oxidative stress
title_sort celastrol attenuates alzheimer s disease mediated learning and memory impairment by inhibiting endoplasmic reticulum stress induced inflammation and oxidative stress
topic alzheimer’s disease
celastrol
endoplasmic reticulum stress
inflammation
oxidative stress
url https://www.archivesofmedicalscience.com/Celastrol-attenuates-Alzheimer-s-disease-mediated-learning-and-memory-impairment,189906,0,2.html
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