Cattle encephalon glycoside and ignotin injection improves cognitive impairment in APPswe/PS1dE9 mice used as multitarget anti-Alzheimer’s drug candidates
Ya Gao,1,* Ya-zhuo Hu,1,* Rui-sheng Li,2 Zhi-tao Han,1 Yan Geng,1 Zheng Xia,1 Wen-jin Du,3 Li-xin Liu,4 Hong-hong Zhang,1 Lu-ning Wang5 1Institute of Geriatrics, Chinese PLA General Hospital, Beijing Key Lab of Normal Aging and Geriatrics, 2Research and Technology Service Center, PLA 302 Hospital,...
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Dove Medical Press
2015
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oai:doaj.org-article:6d2e0c25fc0c44eba19bc6a0b55320dc2021-12-02T00:26:18ZCattle encephalon glycoside and ignotin injection improves cognitive impairment in APPswe/PS1dE9 mice used as multitarget anti-Alzheimer’s drug candidates1178-2021https://doaj.org/article/6d2e0c25fc0c44eba19bc6a0b55320dc2015-02-01T00:00:00Zhttp://www.dovepress.com/cattle-encephalon-glycoside-and-ignotin-injection-improves-cognitive-i-peer-reviewed-article-NDThttps://doaj.org/toc/1178-2021 Ya Gao,1,* Ya-zhuo Hu,1,* Rui-sheng Li,2 Zhi-tao Han,1 Yan Geng,1 Zheng Xia,1 Wen-jin Du,3 Li-xin Liu,4 Hong-hong Zhang,1 Lu-ning Wang5 1Institute of Geriatrics, Chinese PLA General Hospital, Beijing Key Lab of Normal Aging and Geriatrics, 2Research and Technology Service Center, PLA 302 Hospital, 3Department of Neurology, Air Force General Hospital, 4Department of Neurology, Beijing Geriatric Hospital, 5Department of Geriatric Neurology, Chinese PLA General Hospital, Beijing, People’s Republic of China *These authors contributed equally to this work and are joint first authors Background: Cattle encephalon glycoside and ignotin injection (CEGI), a multitargeted neurotrophic drug, has been widely used in the treatment of central and peripheral nerve injuries, such as stroke, hypoxic ischemic encephalopathy, and diabetic neuropathy in the People’s Republic of China. However, data regarding the effect of CEGI on Alzheimer’s disease (AD) remain scarce. The present study aimed to investigate the effect of CEGI on learning and memory in an APPswe/PS1dE9 double-transgenic mouse model, a suitable animal model of AD, and elucidate its possible mechanisms.Materials and methods: Five-month-old APP/PS1 mice were intraperitoneally administered 6.6 mL/kg or 13.2 mL/kg of CEGI for 1 month. After 1 month of administration, all mice received Morris water maze training and a probe test. Mouse brain sections were detected by standard biochemical and immunohistochemical measures.Results: CEGI treatment significantly improved the spatial learning and memory deficits and decreased cerebral amyloid-β42 levels in brain homogenates of APP/PS1 mice. CEGI treatment elevated the activities of superoxide dismutase, and reduced the levels of malondialdehyde. CEGI attenuated neuronal damage in the hippocampus of APP/PS1 mice and upregulated protein and gene expression of Bcl-2 and the ratio of Bcl-2/Bax. CEGI treatment decreased the number of Iba1+ activated microglia in the cortex of the APP/PS1 mice.Conclusion: Our results showed that CEGI prevents memory impairment, possibly by decreasing the amyloid-β42 levels in APP/PS1 mice and inhibiting oxidative stress, apoptosis, and inflammation, making CEGI a promising therapeutic agent for AD. Keywords: Alzheimer’s disease, cognitive impairment, amyloid-β, oxidative stress, apoptosis, inflammationGao YHu YZLi RSHan ZTGeng YXia ZDu WJLiu LXZhang HHWang LNDove Medical PressarticleNeurosciences. Biological psychiatry. NeuropsychiatryRC321-571Neurology. Diseases of the nervous systemRC346-429ENNeuropsychiatric Disease and Treatment, Vol 2015, Iss default, Pp 537-548 (2015) |
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Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Neurology. Diseases of the nervous system RC346-429 |
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Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Neurology. Diseases of the nervous system RC346-429 Gao Y Hu YZ Li RS Han ZT Geng Y Xia Z Du WJ Liu LX Zhang HH Wang LN Cattle encephalon glycoside and ignotin injection improves cognitive impairment in APPswe/PS1dE9 mice used as multitarget anti-Alzheimer’s drug candidates |
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Ya Gao,1,* Ya-zhuo Hu,1,* Rui-sheng Li,2 Zhi-tao Han,1 Yan Geng,1 Zheng Xia,1 Wen-jin Du,3 Li-xin Liu,4 Hong-hong Zhang,1 Lu-ning Wang5 1Institute of Geriatrics, Chinese PLA General Hospital, Beijing Key Lab of Normal Aging and Geriatrics, 2Research and Technology Service Center, PLA 302 Hospital, 3Department of Neurology, Air Force General Hospital, 4Department of Neurology, Beijing Geriatric Hospital, 5Department of Geriatric Neurology, Chinese PLA General Hospital, Beijing, People’s Republic of China *These authors contributed equally to this work and are joint first authors Background: Cattle encephalon glycoside and ignotin injection (CEGI), a multitargeted neurotrophic drug, has been widely used in the treatment of central and peripheral nerve injuries, such as stroke, hypoxic ischemic encephalopathy, and diabetic neuropathy in the People’s Republic of China. However, data regarding the effect of CEGI on Alzheimer’s disease (AD) remain scarce. The present study aimed to investigate the effect of CEGI on learning and memory in an APPswe/PS1dE9 double-transgenic mouse model, a suitable animal model of AD, and elucidate its possible mechanisms.Materials and methods: Five-month-old APP/PS1 mice were intraperitoneally administered 6.6 mL/kg or 13.2 mL/kg of CEGI for 1 month. After 1 month of administration, all mice received Morris water maze training and a probe test. Mouse brain sections were detected by standard biochemical and immunohistochemical measures.Results: CEGI treatment significantly improved the spatial learning and memory deficits and decreased cerebral amyloid-β42 levels in brain homogenates of APP/PS1 mice. CEGI treatment elevated the activities of superoxide dismutase, and reduced the levels of malondialdehyde. CEGI attenuated neuronal damage in the hippocampus of APP/PS1 mice and upregulated protein and gene expression of Bcl-2 and the ratio of Bcl-2/Bax. CEGI treatment decreased the number of Iba1+ activated microglia in the cortex of the APP/PS1 mice.Conclusion: Our results showed that CEGI prevents memory impairment, possibly by decreasing the amyloid-β42 levels in APP/PS1 mice and inhibiting oxidative stress, apoptosis, and inflammation, making CEGI a promising therapeutic agent for AD. Keywords: Alzheimer’s disease, cognitive impairment, amyloid-β, oxidative stress, apoptosis, inflammation |
format |
article |
author |
Gao Y Hu YZ Li RS Han ZT Geng Y Xia Z Du WJ Liu LX Zhang HH Wang LN |
author_facet |
Gao Y Hu YZ Li RS Han ZT Geng Y Xia Z Du WJ Liu LX Zhang HH Wang LN |
author_sort |
Gao Y |
title |
Cattle encephalon glycoside and ignotin injection improves cognitive impairment in APPswe/PS1dE9 mice used as multitarget anti-Alzheimer’s drug candidates |
title_short |
Cattle encephalon glycoside and ignotin injection improves cognitive impairment in APPswe/PS1dE9 mice used as multitarget anti-Alzheimer’s drug candidates |
title_full |
Cattle encephalon glycoside and ignotin injection improves cognitive impairment in APPswe/PS1dE9 mice used as multitarget anti-Alzheimer’s drug candidates |
title_fullStr |
Cattle encephalon glycoside and ignotin injection improves cognitive impairment in APPswe/PS1dE9 mice used as multitarget anti-Alzheimer’s drug candidates |
title_full_unstemmed |
Cattle encephalon glycoside and ignotin injection improves cognitive impairment in APPswe/PS1dE9 mice used as multitarget anti-Alzheimer’s drug candidates |
title_sort |
cattle encephalon glycoside and ignotin injection improves cognitive impairment in appswe/ps1de9 mice used as multitarget anti-alzheimer’s drug candidates |
publisher |
Dove Medical Press |
publishDate |
2015 |
url |
https://doaj.org/article/6d2e0c25fc0c44eba19bc6a0b55320dc |
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