Affiliated Hospital of Liaoning University of Traditional Chinese Medicine Experimental Center of Traditional Chinese Medicine, Shenyang 110032, China.
Liaoning University of Traditional Chinese Medicine, Shenyang 110847, China.
Behav Neurol. 2024 Aug 28;2024:5698119. doi: 10.1155/2024/5698119. eCollection 2024.
The objective of the study is to investigate whether quercetin ameliorates Alzheimer's disease (AD)-like pathology in APP/PS1 double transgenic mice and its hypothesized mechanism, contributing to the comprehension of AD pathogenesis. A total of 30 APP/PS1 transgenic mice were randomized into model group (APP/PS1), quercetin group (APP/PS1+Q), and donepezil hydrochloride group (APP/PS1+DON). Simultaneously, there were 10 C57 mice of the same age served as a control group. Three months posttreatment, the effects of quercetin on AD mice were evaluated using the Morris water maze (MWM) test, Y maze experiment, immunohistochemistry, immunofluorescence, and western blotting. Results from the water maze and Y maze indicated that quercetin significantly improved cognitive impairment in APP/PS1 transgenic AD mice. Additionally, serum enzyme-linked immunosorbent assay (ELISA) results demonstrated that quercetin elevated MDA, superoxide dismutase (SOD), CAT, GSH, acetylcholine (ACh), and acetylcholinesterase (AChE) levels in AD mice. Hematoxylin-eosin (HE) staining, Nissl staining, and hippocampal tissue thioflavine staining revealed that quercetin reduced neuronal damage and A protein accumulation in AD mice. Western blot validated protein expression in the Kelch-like ECH-associated protein 1 (Keap1)/nuclear factor erythroid 2-related factor 2 (Nrf2)/HO-1 pathway associated with oxidative stress and apoptosis, confirming quercetin's potential molecular mechanism of enhancing AD mouse cognition. Furthermore, western blot findings indicate that quercetin significantly alters protein expression in the Keap1/Nrf2/HO-1 pathway. Moreover, molecular docking analysis suggests that Keap1, NQO1, HO-1, caspase-3, Bcl-2, and Bax proteins in the Keap1/Nrf2/HO-1 pathway may be potential regulatory targets of quercetin. These findings will provide a molecular basis for quercetin's clinical application in AD treatment. Quercetin can improve cognitive impairment and AD-like pathology in APP/PS1 double transgenic mice, potentially related to quercetin's activation of the Keap1/Nrf2/HO-1 pathway and reduction of cell apoptosis.
研究目的在于探讨槲皮素是否能改善 APP/PS1 双转基因小鼠的阿尔茨海默病（AD）样病变及其假设机制，从而促进对 AD 发病机制的理解。 共 30 只 APP/PS1 转基因小鼠随机分为模型组（APP/PS1）、槲皮素组（APP/PS1+Q）和多奈哌齐盐酸盐组（APP/PS1+DON）。同时，有 10 只同龄 C57 小鼠作为对照组。治疗 3 个月后，采用 Morris 水迷宫（MWM）试验、Y 迷宫实验、免疫组织化学、免疫荧光和 Western blot 检测槲皮素对 AD 小鼠的作用。 水迷宫和 Y 迷宫的结果表明，槲皮素显著改善了 APP/PS1 转基因 AD 小鼠的认知障碍。此外，血清酶联免疫吸附测定（ELISA）结果表明，槲皮素提高了 AD 小鼠 MDA、超氧化物歧化酶（SOD）、CAT、GSH、乙酰胆碱（ACh）和乙酰胆碱酯酶（AChE）水平。苏木精-伊红（HE）染色、尼氏染色和海马组织硫黄素染色显示，槲皮素减少了 AD 小鼠的神经元损伤和 A 蛋白积累。Western blot 验证了与氧化应激和细胞凋亡相关的 Kelch 样 ECH 相关蛋白 1（Keap1）/核因子红细胞 2 相关因子 2（Nrf2）/血红素加氧酶 1（HO-1）通路中的蛋白表达，证实了槲皮素增强 AD 小鼠认知的潜在分子机制。此外，Western blot 结果表明，槲皮素显著改变了 Keap1/Nrf2/HO-1 通路中的蛋白表达。此外，分子对接分析表明，Keap1/Nrf2/HO-1 通路中的 Keap1、NQO1、HO-1、caspase-3、Bcl-2 和 Bax 蛋白可能是槲皮素的潜在调节靶点。这些发现将为槲皮素在 AD 治疗中的临床应用提供分子基础。 槲皮素可改善 APP/PS1 双转基因小鼠的认知障碍和 AD 样病变，可能与槲皮素激活 Keap1/Nrf2/HO-1 通路和减少细胞凋亡有关。
