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.
Laboratory Animal Department, Kunming Medical University, Kunming, 650031, Yunnan, China.
Eur J Pharmacol. 2024 Oct 15;981:176893. doi: 10.1016/j.ejphar.2024.176893. Epub 2024 Aug 10.
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.
阿尔茨海默病（AD）与淀粉样蛋白-β（Aβ）的神经毒性作用密切相关，导致突触损伤、神经元丧失和认知功能障碍。先前的体外研究表明，柯里拉京具有抵抗 Aβ诱导的氧化应激、炎症损伤以及 Aβ产生中β-位淀粉样前体蛋白裂解酶-1（BACE1）活性的潜力。然而，柯里拉京对阿尔茨海默病的体内保护作用仍未得到探索。本研究旨在探讨柯里拉京对 APP/PS1 小鼠的保护作用及其潜在机制。通过跳台被动回避和 Morris 水迷宫试验评估小鼠的认知功能。尼氏染色用于评估海马神经元的损伤。ELISA 和 Western blot 分析用于确定相关蛋白表达。透射电镜用于观察海马神经元的突触超微结构。高尔基染色用于评估海马锥体神经元的树突形态和树突棘密度。免疫组织化学和 Western blot 用于检测突触相关蛋白的表达。结果表明，柯里拉京改善了 APP/PS1 小鼠的学习和记忆能力，减轻了海马神经元损伤，抑制了 BACE1 并减少了 Aβ的生成。它还改善了突触可塑性和突触相关蛋白的表达。柯里拉京通过抑制 BACE1 有效减少了 Aβ的生成，最终减少了神经元的丧失并增强了突触可塑性，从而改善了突触传递。本研究揭示了柯里拉京在阿尔茨海默病中的潜在治疗作用。
