揭示人参皂苷化合物Mc1在阿尔茨海默病中的治疗潜力探索AMPK/SIRT1/NF-κB信号通路和线粒体功能的作用

IF 2.1 4区 医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL
Qi Yuan, Zhaokun Yang
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引用次数: 0

摘要

背景:阿尔茨海默病(AD)是一种致残性神经退行性疾病,以慢性神经炎症、认知障碍和记忆丧失为特征。目前治疗阿尔茨海默病的方法疗效有限,因此迫切需要替代疗法。尽管人参皂苷在神经退行性疾病中具有良好的疗效,但人参皂苷化合物 Mc1(GCMc1)对 AD 的治疗潜力仍有待深入研究:本研究旨在探讨人参皂苷化合物 Mc1(GCMc1)对 AD 大鼠的治疗潜力,并阐明其作用的分子机制:通过向Sprague Dawley大鼠脑室内注射淀粉样β(Aβ)1-42肽诱发阿尔茨海默病。动物被分为 5 组:1 个对照组和 4 个 AD 亚组,腹腔注射或不注射 10 mg/kg GCMc1 和/或 100 μg/kg 化合物 C。分别使用莫里斯水迷宫(MWM)试验、荧光测定法、酶联免疫吸附试验(ELISA)和免疫印迹技术对行为测试、线粒体功能、炎症细胞因子和蛋白质表达进行了评估:结果:使用人参皂苷化合物 Mc1 可改善认知功能,减少海马 Aβ 的积累,抑制白细胞介素 (IL)-1β、IL-10 和肿瘤坏死因子α (TNF-α) 的水平。人参皂苷化合物 Mc1 降低了线粒体活性氧(ROS)水平和膜去极化,增加了三磷酸腺苷(ATP)水平,上调了 AMPK、PGC-1α 和 SIRT1 蛋白的表达,并下调了核因子-卡巴-B(NF-κB)的表达。重要的是,同时服用 AMPK 抑制剂化合物 C 会减弱 GCMc1 的有益作用,这表明 AMPK 通路参与介导了 GCMc1 的神经保护作用:结论:我们的研究表明,GCMc1 通过调节 AMPK/SIRT1/NF-κB 信号通路,为 AD 大鼠提供了实质性的神经保护。这些发现凸显了 GCMc1 作为一种治疗 AD 的药物的潜力。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Unraveling the therapeutic potential of ginsenoside compound Mc1 in Alzheimer's disease: Exploring the role of AMPK/SIRT1/NF-κB signaling pathway and mitochondrial function.

Background: Alzheimer's disease (AD) is a disabling neurodegenerating disorder characterized by chronic neuroinflammation, cognitive impairment and memory loss. Current treatment options for AD offer limited benefits, underscoring the urgent need for alternative therapeutics. Despite the promising effects of ginsenosides in neurodegenerative diseases, the therapeutic potential of ginsenoside compound Mc1 (GCMc1) in AD remains to be thoroughly investigated.

Objectives: This study aimed to investigate the therapeutic potential of GCMc1 in rats with AD and to elucidate the molecular mechanisms responsible for its effects.

Material and methods: Alzheimer's disease was induced in Sprague Dawley rats through a single intra-cerebro-ventricular injection of amyloid-beta (Aβ)1-42 peptide. The animals were divided into 5 groups: a control group and 4 AD subgroups, with or without receiving 10 mg/kg of GCMc1 and/or 100 μg/kg of compound C intraperitoneally (ip.). Behavioral tests, mitochondrial function, inflammatory cytokines, and proteins expression were evaluated using the Morris water maze (MWM) test, fluorometry, enzyme-linked immunosorbent assay (ELISA), and immunoblotting techniques, respectively.

Results: Treatment with GCMc1 improved cognitive function, reduced hippocampal Aβ accumulation, and suppressed interleukin (IL)-1β, IL-10 and tumor necrosis factor alpha (TNF-α) levels. Ginsenoside compound Mc1 reduced mitochondrial reactive oxygen species (ROS) levels and membrane depolarization, increased adenosine triphosphate (ATP) levels, upregulated the expression of AMPK, PGC-1α and SIRT1 proteins, and downregulated the nuclear factor-kappa-B (NF-κB) expression. Importantly, co-administration of compound C, an AMPK inhibitor, attenuated the beneficial effects of GCMc1, suggesting the involvement of AMPK pathway in mediating GCMc1's neuroprotective effects.

Conclusions: We showed that GCMc1 confers substantial neuroprotection in rats with AD by modulating the AMPK/SIRT1/NF-κB signaling pathway. These findings highlight the potential of GCMc1 as a promising therapeutic agent for AD treatment.

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来源期刊
Advances in Clinical and Experimental Medicine
Advances in Clinical and Experimental Medicine MEDICINE, RESEARCH & EXPERIMENTAL-
CiteScore
3.70
自引率
4.80%
发文量
153
审稿时长
6-12 weeks
期刊介绍: Advances in Clinical and Experimental Medicine has been published by the Wroclaw Medical University since 1992. Establishing the medical journal was the idea of Prof. Bogumił Halawa, Chair of the Department of Cardiology, and was fully supported by the Rector of Wroclaw Medical University, Prof. Zbigniew Knapik. Prof. Halawa was also the first editor-in-chief, between 1992-1997. The journal, then entitled "Postępy Medycyny Klinicznej i Doświadczalnej", appeared quarterly. Prof. Leszek Paradowski was editor-in-chief from 1997-1999. In 1998 he initiated alterations in the profile and cover design of the journal which were accepted by the Editorial Board. The title was changed to Advances in Clinical and Experimental Medicine. Articles in English were welcomed. A number of outstanding representatives of medical science from Poland and abroad were invited to participate in the newly established International Editorial Staff. Prof. Antonina Harłozińska-Szmyrka was editor-in-chief in years 2000-2005, in years 2006-2007 once again prof. Leszek Paradowski and prof. Maria Podolak-Dawidziak was editor-in-chief in years 2008-2016. Since 2017 the editor-in chief is prof. Maciej Bagłaj. Since July 2005, original papers have been published only in English. Case reports are no longer accepted. The manuscripts are reviewed by two independent reviewers and a statistical reviewer, and English texts are proofread by a native speaker. The journal has been indexed in several databases: Scopus, Ulrich’sTM International Periodicals Directory, Index Copernicus and since 2007 in Thomson Reuters databases: Science Citation Index Expanded i Journal Citation Reports/Science Edition. In 2010 the journal obtained Impact Factor which is now 1.179 pts. Articles published in the journal are worth 15 points among Polish journals according to the Polish Committee for Scientific Research and 169.43 points according to the Index Copernicus. Since November 7, 2012, Advances in Clinical and Experimental Medicine has been indexed and included in National Library of Medicine’s MEDLINE database. English abstracts printed in the journal are included and searchable using PubMed http://www.ncbi.nlm.nih.gov/pubmed.
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