WuYou decoction effectively reduces neuronal damage, synaptic dysfunction, and Aβ production in rats exposed to chronic sleep deprivation by modulating the Aβ-related enzymes and SIRT1/Nrf2/NF-κB pathway

IF 4.8 2区医学 Q1 CHEMISTRY, MEDICINAL Journal of ethnopharmacology Pub Date : 2024-10-15 DOI:10.1016/j.jep.2024.118939

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Abstract

Ethnopharmacological relevance

Chronic sleep deprivation (CSD) can result in neuronal damage, synaptic dysfunction, Aβ production, neuroinflammation, and ultimately cognitive deterioration. WuYou Decoction (WYD), a contemporary prescription, has shown promise in enhancing sleep quality and cognitive performance in individuals with insomnia. However, the specific molecular mechanisms responsible for the neuroprotective effects of WYD on CSD remain incompletely understood.

Aim of the study

This study aimed to investigate the neuroprotective effects of WYD on the CSD model and its molecular mechanism.

Materials and methods

UHPLC-MS/MS analysis was utilized to analyze the active ingredients of WYD extract. The study employed the multi-platform water environment method to establish the CSD model in rats. Subsequent to treatment with varying doses of WYD in CSD rats, cognitive function and pathological alterations in hippocampus and cortex, including neuronal damage, synaptic dysfunction, Aβ production, and neuroinflammation, were evaluated through a combination of Morris Water Maze test, HE staining, Nissl staining, Golgi-Cox staining, Transmission electron microscope, ELISA, Immunohistochemistry staining, Immunofluorescence staining and Western blot.

Results

UHPLC-MS/MS analysis revealed a total of 99 active ingredients were identified from the WYD extract. The administration of WYD exhibited a mitigation of cognitive decline in the model of CSD, as evidenced by increased neuron count in the hippocampus and cortex, and improved density and length of dendritic spines in these brain regions. Furthermore, WYD was found to suppress the Aβ production, and inhibit the expression of BACE1, PS1, GFAP, IBA1, IL-1β, IL-6, TNF-α, phosphorylated IκBα (Ser32) and phosphorylated NF-κB p65 (Ser536) in the hippocampus and cortex, while also increasing the levels of PSD95, SYN1, ADAM10, IDE, SIRT1 and Nrf2.

Conclusions

WYD exhibits neuroprotective properties in CSD, potentially through modulation of the Aβ-related enzymes and SIRT1/Nrf2/NF-κB pathway.

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乌药煎剂通过调节 Aβ 相关酶和 SIRT1/Nrf2/NF-κB 通路，有效减轻慢性睡眠剥夺大鼠的神经元损伤、突触功能障碍和 Aβ 生成

民族药理学意义长期睡眠不足（CSD）会导致神经元损伤、突触功能障碍、Aβ生成、神经炎症，并最终导致认知功能退化。乌药煎剂（WYD）作为一种现代处方药，在提高失眠患者的睡眠质量和认知能力方面显示出了良好的前景。本研究旨在探讨五味子对 CSD 模型的神经保护作用及其分子机制。材料与方法采用 UHPLC-MS/MS 分析方法分析五味子提取物的有效成分。研究采用多平台水环境法建立大鼠 CSD 模型。通过莫里斯水迷宫试验、HE染色、Nissl染色、Golgi-Cox染色、透射电子显微镜、ELISA、免疫组织化学染色、免疫荧光染色和Western印迹等方法，对CSD大鼠进行不同剂量的WYD治疗后，认知功能以及海马和皮层的病理改变，包括神经元损伤、突触功能障碍、Aβ生成和神经炎症等进行评估。结果UHPLC-MS/MS分析表明，世青提取物中共鉴定出99种有效成分。服用 WYD 可减轻 CSD 模型中的认知能力下降，这体现在海马和皮层神经元数量的增加，以及这些脑区树突棘密度和长度的改善。此外，研究还发现 WYD 可抑制 Aβ 的产生，并抑制海马和皮层中 BACE1、PS1、GFAP、IBA1、IL-1β、IL-6、TNF-α、磷酸化 IκBα (Ser32) 和磷酸化 NF-κB p65 (Ser536) 的表达，同时还可提高 PSD95、SYN1、ADAM10、IDE、SIRT1 和 Nrf2 的水平。结论WYD对CSD具有神经保护作用，这可能是通过调节Aβ相关酶和SIRT1/Nrf2/NF-κB途径实现的。

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

Journal of ethnopharmacology 医学-全科医学与补充医学

CiteScore

10.30

自引率

5.60%

发文量

967

审稿时长

77 days

期刊介绍： The Journal of Ethnopharmacology is dedicated to the exchange of information and understandings about people''s use of plants, fungi, animals, microorganisms and minerals and their biological and pharmacological effects based on the principles established through international conventions. Early people confronted with illness and disease, discovered a wealth of useful therapeutic agents in the plant and animal kingdoms. The empirical knowledge of these medicinal substances and their toxic potential was passed on by oral tradition and sometimes recorded in herbals and other texts on materia medica. Many valuable drugs of today (e.g., atropine, ephedrine, tubocurarine, digoxin, reserpine) came into use through the study of indigenous remedies. Chemists continue to use plant-derived drugs (e.g., morphine, taxol, physostigmine, quinidine, emetine) as prototypes in their attempts to develop more effective and less toxic medicinals.