{"title":"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","authors":"","doi":"10.1016/j.jep.2024.118939","DOIUrl":null,"url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>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.</div></div><div><h3>Aim of the study</h3><div>This study aimed to investigate the neuroprotective effects of WYD on the CSD model and its molecular mechanism.</div></div><div><h3>Materials and methods</h3><div>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.</div></div><div><h3>Results</h3><div>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.</div></div><div><h3>Conclusions</h3><div>WYD exhibits neuroprotective properties in CSD, potentially through modulation of the Aβ-related enzymes and SIRT1/Nrf2/NF-κB pathway.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":null,"pages":null},"PeriodicalIF":4.8000,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"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\",\"authors\":\"\",\"doi\":\"10.1016/j.jep.2024.118939\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Ethnopharmacological relevance</h3><div>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.</div></div><div><h3>Aim of the study</h3><div>This study aimed to investigate the neuroprotective effects of WYD on the CSD model and its molecular mechanism.</div></div><div><h3>Materials and methods</h3><div>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.</div></div><div><h3>Results</h3><div>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.</div></div><div><h3>Conclusions</h3><div>WYD exhibits neuroprotective properties in CSD, potentially through modulation of the Aβ-related enzymes and SIRT1/Nrf2/NF-κB pathway.</div></div>\",\"PeriodicalId\":15761,\"journal\":{\"name\":\"Journal of ethnopharmacology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":4.8000,\"publicationDate\":\"2024-10-15\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of ethnopharmacology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0378874124012388\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CHEMISTRY, MEDICINAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of ethnopharmacology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0378874124012388","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}
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
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.
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.