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黄精皂苷通过调节c-Abl/MST1通路抑制阿尔茨海默病小鼠的神经元凋亡并改善认知缺陷。

Saponin of Rhizoma Polygonati inhibits neuronal apoptosis and ameliorates cognitive deficits in Alzheimer's disease mice by modulating c-Abl/MST1 pathway.

作者信息

Zhang Changying, Tang Xudong, Wu Shixing

机构信息

Department of Neurology, The Second People's Hospital of Hunan Province (Brain Hospital of Hunan Province), Changsha, Hunan Province, China.

Department of clinical Laboratory, The Second People's Hospital of Hunan Province (Brain Hospital of Hunan Province), Changsha, Hunan Province, China.

出版信息

Gen Physiol Biophys. 2025 Nov;44(6):451-465. doi: 10.4149/gpb_2025032.

DOI:10.4149/gpb_2025032
PMID:41217224
Abstract

Saponin of Rhizoma Polygonati (SRP) is a key bioactive component obtained from Rhizoma Polygonati, has neuroprotection, antioxidant and anticancer effects. This research aimed to explore whether SRP improves cognitive deficits in Alzheimer's disease (AD) mice. Behavioral testing was performed by the Morris water maze test. Histopathological changes and neuronal apoptosis in mouse hippocampus were observed by Hematoxylin-eosin, Nissl staining, and TUNEL staining. The impact of SRP on amyloid β-protein (Aβ) and neurofibrillary tangles (NFTs) production was determined by immunofluorescence and Glycine silver staining. Western blot detected c-Abl/Mammalian sterile 20 (STE20)-like kinase 1 (MST1) pathway, apoptosis-related protein, and Tau phosphorylation level. AD mice exhibit cognitive deficits compared to normal mice, and SRP ameliorates cognitive deficits. The hippocampal tissues of AD mice showed neuronal damage and apoptosis, with Aβ deposition, loss of Nissl bodies and formation of NFTs. SRP attenuated neuronal damage in AD mice, inhibited Aβ deposition and NFTs formation. Additionally, SRP blocked the c-Abl/MST1 pathway in AD mice. c-Abl inhibitor enhanced the neuroprotective effect of SRP in AD mice, while c-Abl agonist weakened this effect. SRP inhibits hippocampal histopathological damage and enhances cognitive ability in AD mice through blocking the c-Abl/MST1 pathway.

摘要

黄精皂苷(SRP)是从黄精中提取的一种关键生物活性成分,具有神经保护、抗氧化和抗癌作用。本研究旨在探讨SRP是否能改善阿尔茨海默病(AD)小鼠的认知缺陷。通过莫里斯水迷宫试验进行行为测试。采用苏木精-伊红染色、尼氏染色和TUNEL染色观察小鼠海马组织的病理组织学变化和神经元凋亡情况。通过免疫荧光和甘氨酸银染色确定SRP对淀粉样β蛋白(Aβ)和神经原纤维缠结(NFTs)产生的影响。蛋白质免疫印迹法检测c-Abl/哺乳动物不育20(STE20)样激酶1(MST1)通路、凋亡相关蛋白和Tau蛋白磷酸化水平。与正常小鼠相比,AD小鼠表现出认知缺陷,而SRP可改善认知缺陷。AD小鼠的海马组织显示神经元损伤和凋亡,伴有Aβ沉积、尼氏体丢失和NFTs形成。SRP减轻了AD小鼠的神经元损伤,抑制了Aβ沉积和NFTs形成。此外,SRP阻断了AD小鼠的c-Abl/MST1通路。c-Abl抑制剂增强了SRP对AD小鼠的神经保护作用,而c-Abl激动剂则削弱了这种作用。SRP通过阻断c-Abl/MST1通路抑制AD小鼠海马组织的病理组织学损伤并提高其认知能力。

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