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荜澄茄醇通过 AMPK/mTOR 通路对 Aβ寡聚体诱导 AD 小鼠认知功能障碍的作用及机制。

The effect and mechanism of patchouli alcohol on cognitive dysfunction in AD mice induced by Aβ oligomers through AMPK/mTOR pathway.

机构信息

School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, PR China.

Second Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, PR China; The Second Affiliated Hospital of Guangzhou University of Chinese Medicine Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, PR China.

出版信息

Brain Res Bull. 2024 Sep;215:111030. doi: 10.1016/j.brainresbull.2024.111030. Epub 2024 Jul 10.

Abstract

Alzheimer's disease (AD) is a neurodegenerative brain disorder that progressively impairs long-term and working memory. The function and mechanism of PA(Patchouli alcohol) in improving AD in the external treatment of encephalopathy remain unclear. This study aimed to investigate the therapeutic effect of PA on AD using an Aβ induced AD mouse model with LPS(Lipopolysaccharide) stimulation of BV2 microglial cells. Additionally, we aimed to explore the potential mechanism of PA in enhancing autophagy and reducing neuroinflammation through the AMPK (AMP-activated protein kinase)/mTOR (Mammaliam target of rapamycin) signaling pathway. The Morris water maze was used to assess cognitive function, and cortical and hippocampal tissues were collected for further analysis of the corresponding signaling pathways and inflammatory changes through biological experiments. Our research findings demonstrate that PA has a significant positive impact on cognitive and memory impairments in mice that have been induced with Aβ-induced AD. Additionally, PA was also found to revert the activation of microglia induced by LPS. These effects may be attributed to the reduction of neuroinflammation and enhancement of the AMPK/mTOR autophagy pathway. Therefore, PA may serve as an effective therapeutic option to prevent or delay the progression of AD-associated memory dysfunction.

摘要

阿尔茨海默病(AD)是一种神经退行性脑疾病,会逐渐损害长期记忆和工作记忆。PA(广藿香醇)在脑病外部治疗中改善 AD 的功能和机制尚不清楚。本研究旨在通过 LPS(脂多糖)刺激 BV2 小胶质细胞的 Aβ诱导 AD 小鼠模型来研究 PA 对 AD 的治疗作用。此外,我们旨在通过 AMPK(AMP 激活蛋白激酶)/mTOR(哺乳动物雷帕霉素靶蛋白)信号通路探索 PA 通过增强自噬和减少神经炎症来增强 AD 的潜在机制。通过 Morris 水迷宫来评估认知功能,通过生物实验收集皮质和海马组织,进一步分析相应的信号通路和炎症变化。我们的研究结果表明,PA 对 Aβ诱导的 AD 小鼠的认知和记忆损伤有显著的积极影响。此外,PA 还能逆转 LPS 诱导的小胶质细胞的激活。这些作用可能归因于神经炎症的减少和 AMPK/mTOR 自噬途径的增强。因此,PA 可能是预防或延缓 AD 相关记忆功能障碍进展的有效治疗选择。

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