Polygonatum sibiricum polysaccharide ameliorates neurotoxicity in Alzheimer disease mice by inhibiting endoplasmic reticulum stress and lipid raft formation through AMPK/GSK3β/Nrf2 pathway.

IF 1.5 4区医学 Q3 CLINICAL NEUROLOGY

Neurological Research Pub Date : 2025-09-13 DOI:10.1080/01616412.2025.2559431

Shixing Wu, Wei Liu, Changying Zhang

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引用次数: 0

Abstract

Background: Polygonatum sibiricum polysaccharide (PSP) is known for its anti-inflammatory and cognitive improvement effects. However, its potential to alleviate neurotoxicity in Alzheimer's diseafse (AD) has not been thoroughly explored. This study aims to investigate the effects of PSP on AD and clarify its underlying mechanisms.

Methods: Behavioral tests were conducted using Y-maze and Morris water maze in SAMP8 and SAMR1 mice. Histopathological changes were assessed via ThT and TUNEL staining. Immunofluorescence co-localization and ELISA measured amyloid β-protein (Aβ) levels and inflammatory cytokines. Microglia and astrocyte activation were detected by immunohistochemistry. Oxidative stress and the AMPK/GSK3β/Nrf2 pathway were examined through Western blot.

Results: SAMP8 mice exhibited impaired learning and memory, significantly improved by PSP. PSP reduced amyloid plaque load, neuroinflammation, microglia/astrocyte activation, oxidative stress, and neuronal apoptosis in SAMP8 mice. PSP inhibited Aβ production and lipid raft formation in the endoplasmic reticulum-mitochondrial membrane. Activation of the AMPK/GSK3β/Nrf2 pathway was observed, with AMPK inhibition reducing PSP's protective effects.

Conclusion: PSP alleviates neurotoxicity in AD model mice by inhibiting ER stress and lipid raft formation via the AMPK/GSK3β/Nrf2 pathway.

查看原文本刊更多论文

黄精多糖通过AMPK/GSK3β/Nrf2通路抑制内质网应激和脂质筏形成，改善阿尔茨海默病小鼠的神经毒性。

背景：黄精多糖（PSP）具有抗炎和改善认知的作用。然而，其减轻阿尔茨海默病（AD）神经毒性的潜力尚未得到充分探讨。本研究旨在探讨PSP对AD的影响并阐明其潜在机制。方法：采用y型迷宫和Morris水迷宫对SAMP8和SAMR1小鼠进行行为学测试。通过ThT和TUNEL染色评估组织病理学变化。免疫荧光共定位和ELISA检测淀粉样蛋白β (Aβ)水平和炎症因子。免疫组化检测小胶质细胞和星形胶质细胞活化情况。Western blot检测氧化应激和AMPK/GSK3β/Nrf2通路。结果：SAMP8小鼠表现出学习和记忆受损，PSP治疗后明显改善。PSP降低了SAMP8小鼠的淀粉样斑块负荷、神经炎症、小胶质细胞/星形胶质细胞活化、氧化应激和神经元凋亡。PSP抑制内质网-线粒体膜中Aβ的产生和脂筏的形成。AMPK/GSK3β/Nrf2通路被激活，AMPK的抑制降低了PSP的保护作用。结论：PSP通过AMPK/GSK3β/Nrf2通路抑制内质网应激和脂质筏形成，减轻AD模型小鼠的神经毒性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Neurological Research 医学-临床神经学

CiteScore

3.60

自引率

0.00%

发文量

116

审稿时长

5.3 months

期刊介绍： Neurological Research is an international, peer-reviewed journal for reporting both basic and clinical research in the fields of neurosurgery, neurology, neuroengineering and neurosciences. It provides a medium for those who recognize the wider implications of their work and who wish to be informed of the relevant experience of others in related and more distant fields. The scope of the journal includes: •Stem cell applications •Molecular neuroscience •Neuropharmacology •Neuroradiology •Neurochemistry •Biomathematical models •Endovascular neurosurgery •Innovation in neurosurgery.