CZYH Alleviates β-Amyloid-Induced Cognitive Impairment and Inflammation Response via Modulation of JNK and NF-κB Pathway in Rats

Cu-Zhi-Yi-Hao (CZYH), an empirical formula of traditional Chinese medicine (TCM), has been used for amnesia treatment in clinical practice. However, its underlying pharmacological mechanism has not been fully illuminated. The current study was designed to investigate the neuroprotective effect of CZ...

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Main Authors: Yuanyuan Deng, Lianzhi Ye, Cheng Yu, Caixia Yin, Jingshan Shi, Qihai Gong
Format: Article
Language:English
Published: Wiley 2019-01-01
Series:Behavioural Neurology
Online Access:http://dx.doi.org/10.1155/2019/9546761
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author Yuanyuan Deng
Lianzhi Ye
Cheng Yu
Caixia Yin
Jingshan Shi
Qihai Gong
author_facet Yuanyuan Deng
Lianzhi Ye
Cheng Yu
Caixia Yin
Jingshan Shi
Qihai Gong
author_sort Yuanyuan Deng
collection DOAJ
description Cu-Zhi-Yi-Hao (CZYH), an empirical formula of traditional Chinese medicine (TCM), has been used for amnesia treatment in clinical practice. However, its underlying pharmacological mechanism has not been fully illuminated. The current study was designed to investigate the neuroprotective effect of CZYH on a β-amyloid 25-35- (Aβ25-35-) induced learning and memory deficit rat model. CZYH (200, 400, or 800 mg/kg), donepezil (1.0 mg/kg), or distilled water was given to Aβ25-35-stimulated animals for 17 days consecutively. The Morris water maze test revealed that CZYH (400 or 800 mg/kg) administration improved the Aβ25-35-induced cognitive impairments in rats, and Nissl staining demonstrated that CZYH mitigated the Aβ-caused neuron loss. In addition, CZYH treatment markedly inhibited the activation of microglia as evidenced by a decreased level of IBA-1 and increased YM-1/2 protein expression. The protein expression levels of TNF-α, IL-1β, and COX-2 were also repressed by CZYH. Besides, CZYH treatment alleviated Aβ-induced IκB-α degradation and NF-κB p65 phosphorylation, as well as reduced the JNK phosphorylation level. In conclusion, the present study suggests that CZYH could improve learning and memory abilities and relieve neuron loss in Aβ25-35-induced rats, at least partly through inhibition of the neuroinflammatory response via inhibiting the JNK-dependent NF-κB activation, indicating that CZYH might be a promising formula for the treatment of AD.
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spelling doaj-art-992ab2cd09194a948e223fecfa081b392025-02-03T01:28:26ZengWileyBehavioural Neurology0953-41801875-85842019-01-01201910.1155/2019/95467619546761CZYH Alleviates β-Amyloid-Induced Cognitive Impairment and Inflammation Response via Modulation of JNK and NF-κB Pathway in RatsYuanyuan Deng0Lianzhi Ye1Cheng Yu2Caixia Yin3Jingshan Shi4Qihai Gong5Key Laboratory of Basic Pharmacology of Ministry of Education, Department of Pharmacology, Zunyi Medical University, Zunyi, Guizhou 563000, ChinaKey Laboratory of Basic Pharmacology of Ministry of Education, Department of Pharmacology, Zunyi Medical University, Zunyi, Guizhou 563000, ChinaKey Laboratory of Basic Pharmacology of Ministry of Education, Department of Pharmacology, Zunyi Medical University, Zunyi, Guizhou 563000, ChinaKey Laboratory of Basic Pharmacology of Ministry of Education, Department of Pharmacology, Zunyi Medical University, Zunyi, Guizhou 563000, ChinaKey Laboratory of Basic Pharmacology of Ministry of Education, Department of Pharmacology, Zunyi Medical University, Zunyi, Guizhou 563000, ChinaKey Laboratory of Basic Pharmacology of Ministry of Education, Department of Pharmacology, Zunyi Medical University, Zunyi, Guizhou 563000, ChinaCu-Zhi-Yi-Hao (CZYH), an empirical formula of traditional Chinese medicine (TCM), has been used for amnesia treatment in clinical practice. However, its underlying pharmacological mechanism has not been fully illuminated. The current study was designed to investigate the neuroprotective effect of CZYH on a β-amyloid 25-35- (Aβ25-35-) induced learning and memory deficit rat model. CZYH (200, 400, or 800 mg/kg), donepezil (1.0 mg/kg), or distilled water was given to Aβ25-35-stimulated animals for 17 days consecutively. The Morris water maze test revealed that CZYH (400 or 800 mg/kg) administration improved the Aβ25-35-induced cognitive impairments in rats, and Nissl staining demonstrated that CZYH mitigated the Aβ-caused neuron loss. In addition, CZYH treatment markedly inhibited the activation of microglia as evidenced by a decreased level of IBA-1 and increased YM-1/2 protein expression. The protein expression levels of TNF-α, IL-1β, and COX-2 were also repressed by CZYH. Besides, CZYH treatment alleviated Aβ-induced IκB-α degradation and NF-κB p65 phosphorylation, as well as reduced the JNK phosphorylation level. In conclusion, the present study suggests that CZYH could improve learning and memory abilities and relieve neuron loss in Aβ25-35-induced rats, at least partly through inhibition of the neuroinflammatory response via inhibiting the JNK-dependent NF-κB activation, indicating that CZYH might be a promising formula for the treatment of AD.http://dx.doi.org/10.1155/2019/9546761
spellingShingle Yuanyuan Deng
Lianzhi Ye
Cheng Yu
Caixia Yin
Jingshan Shi
Qihai Gong
CZYH Alleviates β-Amyloid-Induced Cognitive Impairment and Inflammation Response via Modulation of JNK and NF-κB Pathway in Rats
Behavioural Neurology
title CZYH Alleviates β-Amyloid-Induced Cognitive Impairment and Inflammation Response via Modulation of JNK and NF-κB Pathway in Rats
title_full CZYH Alleviates β-Amyloid-Induced Cognitive Impairment and Inflammation Response via Modulation of JNK and NF-κB Pathway in Rats
title_fullStr CZYH Alleviates β-Amyloid-Induced Cognitive Impairment and Inflammation Response via Modulation of JNK and NF-κB Pathway in Rats
title_full_unstemmed CZYH Alleviates β-Amyloid-Induced Cognitive Impairment and Inflammation Response via Modulation of JNK and NF-κB Pathway in Rats
title_short CZYH Alleviates β-Amyloid-Induced Cognitive Impairment and Inflammation Response via Modulation of JNK and NF-κB Pathway in Rats
title_sort czyh alleviates β amyloid induced cognitive impairment and inflammation response via modulation of jnk and nf κb pathway in rats
url http://dx.doi.org/10.1155/2019/9546761
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