Zexieyin formula alleviates Alzheimer's disease via post-synaptic CaMKII modulating AMPA receptor: Involved in promoting neurogenesis to strengthen synaptic plasticity in mice hippocampus.

Autor: Sun Y; Key Laboratory of Integrative Biomedicine for Brain Diseases, School of Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, PR China; National Famous Chinese Medicine Expert Inheritance Studio (Meng Jingchun), Nanjing University of Chinese Medicine, School of Chinese Medicine, Nanjing 210023, PR China., Zhang H; Interdisciplinary Institute for Personalized Medicine in Brain Disorders, Jinan University, Guangzhou 510632, PR China. Electronic address: hailouzhang_2021@yeah.net., Liu R; Key Laboratory of Integrative Biomedicine for Brain Diseases, School of Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, PR China; National Famous Chinese Medicine Expert Inheritance Studio (Meng Jingchun), Nanjing University of Chinese Medicine, School of Chinese Medicine, Nanjing 210023, PR China; Interdisciplinary Institute for Personalized Medicine in Brain Disorders, Jinan University, Guangzhou 510632, PR China., Wang Y; Key Laboratory of Integrative Biomedicine for Brain Diseases, School of Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, PR China; National Famous Chinese Medicine Expert Inheritance Studio (Meng Jingchun), Nanjing University of Chinese Medicine, School of Chinese Medicine, Nanjing 210023, PR China., Zhang X; Key Laboratory of Integrative Biomedicine for Brain Diseases, School of Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, PR China; National Famous Chinese Medicine Expert Inheritance Studio (Meng Jingchun), Nanjing University of Chinese Medicine, School of Chinese Medicine, Nanjing 210023, PR China., Huang R; Key Laboratory of Integrative Biomedicine for Brain Diseases, School of Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, PR China; National Famous Chinese Medicine Expert Inheritance Studio (Meng Jingchun), Nanjing University of Chinese Medicine, School of Chinese Medicine, Nanjing 210023, PR China., Zhu B; Key Laboratory of Integrative Biomedicine for Brain Diseases, School of Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, PR China; National Famous Chinese Medicine Expert Inheritance Studio (Meng Jingchun), Nanjing University of Chinese Medicine, School of Chinese Medicine, Nanjing 210023, PR China. Electronic address: zhuboran@njucm.edu.cn., Wu H; Key Laboratory of Integrative Biomedicine for Brain Diseases, School of Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, PR China; National Famous Chinese Medicine Expert Inheritance Studio (Meng Jingchun), Nanjing University of Chinese Medicine, School of Chinese Medicine, Nanjing 210023, PR China. Electronic address: haoxinwu@njucm.edu.cn.
Jazyk: angličtina
Zdroj: Phytomedicine : international journal of phytotherapy and phytopharmacology [Phytomedicine] 2024 Aug; Vol. 131, pp. 155802. Date of Electronic Publication: 2024 Jun 04.
DOI: 10.1016/j.phymed.2024.155802
Abstrakt: Background: Alzheimer's disease (AD) is a serious neurodegenerative disease and brings a serious burden to society and families. Due to lack of effective drugs for the treatment of AD, it's urgent to develop new and effective drug for the treatment of AD.
Purpose: The study aimed to investigate the potential of Zexieyin formula (ZXYF), a Chinese medicine formula, for the treatment of AD and its potential mechanism of action.
Methods: We used chronic scopolamine (SCOP) induction mice model and APP/PS1 mice to reveal and confirm ZXYF for the treatment of AD with donepezil (DON) as a positive reference. The learning and memory function were detected by morris water maze test (MWM) and y-maze test. Moreover, western blot and immunofluorescence were used to detect the molecular mechanism of ZXYF for the alleviation of AD in hippocampus. Lastly, pharmacological technology was applied to evaluate AMPA receptor involved in the role of ZXYF in the treatment of AD.
Results: The results showed that ZXYF could improve memory and learning deficits both in two AD models including scopolamine (SCOP)-induced mice model and APP/PS1mice. Moreover, ZXYF or not DON increased expressions of BrdU/DCX and Ki67 positive cells in dentate gyrus (DG), up-regulated the levels of AMPA subunit type (GluA1) and PKA in hippocampus in SCOP-induced mice model, although ZXYF and DON activated CaMKII, CaMKII-phosphorylation, CREB, CREB-phosphorylation and PSD95 in hippocampus in SCOP-induced mice model. ZXYF also activated CaMKII, CaMKII-phosphorylation and GluA1 in HT22 cells. Furthermore, transient inhibiting AMPA receptor was capable of blocking the effects of ZXYF to treat AD in MWM and suppressing the number of BrdU/DCX positive cells increased by ZXYF in DG in SCOP-induced mice model, but had no effect on the alteration of Ki67 positive cells.
Conclusion: ZXYF had the therapeutic effects on AD-treatment, which activated CaMKII to promote AMPA receptor (GluA1) and subsequently up-regulated PKA/CREB signaling to facilitate neurogenesis to achieve enhanced postsynaptic protein.
Competing Interests: Declaration of competing interest The authors declare no conflict of interest.
(Copyright © 2024. Published by Elsevier GmbH.)
Databáze: MEDLINE
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