Corilagin improves cognitive impairment in APP/PS1 mice by reducing Aβ generation and enhancing synaptic plasticity.

Autor: Chen L; School of Pharmaceutical Sciences, Yunnan Key Laboratory of Pharmacology for Natural Products, NHC Key Laboratory of Drug Addiction Medicine, Kunming Medical University, Kunming, 650500, China; Yunnan College of Modern Biomedical Industry, Kunming Medical University, Kunming, 650500, China., Zhuang Z; School of Pharmaceutical Sciences, Yunnan Key Laboratory of Pharmacology for Natural Products, NHC Key Laboratory of Drug Addiction Medicine, Kunming Medical University, Kunming, 650500, China; Yunnan College of Modern Biomedical Industry, Kunming Medical University, Kunming, 650500, China., Duan H; School of Pharmaceutical Sciences, Yunnan Key Laboratory of Pharmacology for Natural Products, NHC Key Laboratory of Drug Addiction Medicine, Kunming Medical University, Kunming, 650500, China; Yunnan College of Modern Biomedical Industry, Kunming Medical University, Kunming, 650500, China., Lv D; School of Pharmaceutical Sciences, Yunnan Key Laboratory of Pharmacology for Natural Products, NHC Key Laboratory of Drug Addiction Medicine, Kunming Medical University, Kunming, 650500, China; Yunnan College of Modern Biomedical Industry, Kunming Medical University, Kunming, 650500, China., Hong S; Laboratory Animal Department, Kunming Medical University, Kunming, 650031, Yunnan, China., Chen P; School of Pharmaceutical Sciences, Yunnan Key Laboratory of Pharmacology for Natural Products, NHC Key Laboratory of Drug Addiction Medicine, Kunming Medical University, Kunming, 650500, China; Yunnan College of Modern Biomedical Industry, Kunming Medical University, Kunming, 650500, China. Electronic address: chenpeng@kmmu.edu.cn., He B; School of Pharmaceutical Sciences, Yunnan Key Laboratory of Pharmacology for Natural Products, NHC Key Laboratory of Drug Addiction Medicine, Kunming Medical University, Kunming, 650500, China; Yunnan College of Modern Biomedical Industry, Kunming Medical University, Kunming, 650500, China. Electronic address: hebo@kmmu.edu.cn., Shen Z; School of Pharmaceutical Sciences, Yunnan Key Laboratory of Pharmacology for Natural Products, NHC Key Laboratory of Drug Addiction Medicine, Kunming Medical University, Kunming, 650500, China; Yunnan College of Modern Biomedical Industry, Kunming Medical University, Kunming, 650500, China. Electronic address: shenzhiqiang@kmmu.edu.cn.
Jazyk: angličtina
Zdroj: European journal of pharmacology [Eur J Pharmacol] 2024 Oct 15; Vol. 981, pp. 176893. Date of Electronic Publication: 2024 Aug 10.
DOI: 10.1016/j.ejphar.2024.176893
Abstrakt: Alzheimer's disease (AD) is closely associated with the neurotoxic effects of amyloid-β (Aβ), leading to synaptic damage, neuronal loss and cognitive dysfunction. Previous in vitro studies have demonstrated the potential of corilagin to counteract Aβ-induced oxidative stress, inflammatory injury, and β-site amyloid precursor protein cleaving enzyme-1 (BACE1) activity in Aβ production. However, the in vivo protective effects of corilagin on Alzheimer's disease remain unexplored. The purpose of this study was to investigate the protective effects of corilagin on APP/PS1 mice and the underlying mechanisms. The cognitive function of the mice was assessed by step-through passive avoidance and Morris water maze tests. Nissl staining was used to evaluate neuronal damage in the hippocampus. ELISA and Western blotting analyses were used to determine the associated protein expression. Transmission electron microscopy was utilized to observe the synaptic ultrastructure of hippocampal neurons. Golgi staining was applied to assess dendritic morphology and dendritic spine density in hippocampal pyramidal neurons. Immunohistochemistry and Western blotting were performed to examine the expression of synaptic-associated proteins. The results showed that corilagin improves learning and memory in APP/PS1 mice, reduces hippocampal neuron damage, inhibits BACE1 and reduces Aβ generation. It also improves synaptic plasticity and the expression of synaptic-associated proteins. Corilagin effectively reduces Aβ generation by inhibiting BACE1, ultimately reducing neuronal loss and enhancing synaptic plasticity to improve synaptic transmission. This study sheds light on the potential therapeutic role of corilagin in Alzheimer's disease.
Competing Interests: Declaration of competing interest No conflicts of interest are declared by the authors.
(Copyright © 2024 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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