Yan Chen , Yan Zhu , Zihu Tan , Xueyi Zhang , Jiafeng Hu , Ruichi Zhu , Minjie Xie , Jing Wang , Lizhu Chen , Zhenli Guo
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引用次数: 0
Abstract
Ethnopharmacological relevance
Alzheimer's disease (AD) is a prevalent neurodegenerative disorder characterized by progressive cognitive decline and behavioral impairments in the elderly. Microglia, the resident immune cells of the central nervous system, play a crucial role in modulating the pathological processes associated with AD. Jiajian Shuyu Pills (JJSYP) are frequently employed in the treatment of AD, purportedly by enhancing the physiological functions of human tissues and organs to modulate the immune response. Nevertheless, the underlying mechanisms by which JJSYP exert their therapeutic effects in the context of AD remain inadequately elucidated.
Aim of the study
This study aimed to assess the effects of JJSYP on cognitive enhancement and the alleviation of neuroinflammation in the treatment of AD, as well as to explore the underlying mechanisms using mouse models.
Materials and methods
The components of JJSYP in serum were analyzed using HPLC-Q/TOF-MS. APP/PS1 transgenic mice served as AD models in this investigation. Cognitive function in the AD mice was assessed through the Mirror Water Maze Test and the Novel Object Recognition Test. The quantification of apoptotic hippocampal cells was conducted using Nissl staining and TUNEL staining. Immunofluorescence (IF) and Western blot (WB) analyses were employed to examine microglial activation and the expression of relevant proteins. Transcriptomic sequencing analysis and network pharmacology were administrated to explore the potential mechanisms of JJSYP in AD treatment. Inflammatory cytokine levels in the brain were measured using RT-PCR.
Results
A total of 74 absorbed prototype components from JJSYP were identified. JJSYP effectively improved cognitive function and neuroapoptosis in AD model mice by modulating the activation of microglia. The JJSYP intervention alleviated neuroinflammation by suppressing microglial activation and reducing the accumulation of amyloid β-protein. Through transcriptome sequencing and WB verification, 34 differentially expressed genes (DEGs) were identified, including ACKR3, NR1H3 and Adra1a. Following treatment with a high dose of JJSYP, both ACKR3 and NR1H3 showed a significant decrease compared to the model group. Conversely, ADRA1A expression was reduced in model group compared to the control group, but increased following high dose JJSYP treatment. Research involving RNA sequencing and network pharmacology indicated that JJSYP altered the activation of CXCL12/ACKR3 signaling pathways in the hippocampus.
Conclusions
JJSYP exhibits potential anti-Alzheimer's Disease effects and warrants further investigation and development as a prosper treatment for AD.
阿尔茨海默病（AD）是一种常见的神经退行性疾病，以老年人进行性认知能力下降和行为障碍为特征。小胶质细胞是中枢神经系统的常驻免疫细胞，在调节与AD相关的病理过程中起着至关重要的作用。加健疏郁丸（JJSYP）常用于治疗阿尔茨海默病，据称是通过增强人体组织和器官的生理功能来调节免疫反应。然而，JJSYP在阿尔茨海默病中发挥其治疗作用的潜在机制仍未得到充分阐明。本研究旨在通过小鼠模型，评估JJSYP在AD治疗中对认知增强和神经炎症减轻的作用，并探讨其潜在机制。材料与方法采用HPLC-Q/TOF-MS分析血清中JJSYP的成分。APP/PS1转基因小鼠作为AD模型。通过镜面水迷宫实验和新物体识别实验评估AD小鼠的认知功能。采用尼氏染色和TUNEL染色对海马细胞凋亡进行定量。采用免疫荧光（IF）和Western blot （WB）检测小胶质细胞的活化和相关蛋白的表达。通过转录组测序分析和网络药理学方法探讨JJSYP治疗AD的潜在机制。用RT-PCR法测定脑内炎症细胞因子水平。结果共鉴定出参芪多糖中吸收的原型成分74种。JJSYP通过调节小胶质细胞的激活，有效改善AD模型小鼠的认知功能和神经细胞凋亡。JJSYP干预通过抑制小胶质细胞激活和减少淀粉样β-蛋白的积累来减轻神经炎症。通过转录组测序和WB验证，鉴定出34个差异表达基因（DEGs），包括ACKR3、NR1H3和Adra1a。高剂量JJSYP治疗后，ACKR3和NR1H3均较模型组显著降低。相反，与对照组相比，模型组ADRA1A表达降低，但高剂量JJSYP治疗后ADRA1A表达升高。涉及RNA测序和网络药理学的研究表明，JJSYP改变了海马CXCL12/ACKR3信号通路的激活。结论sjjsyp具有潜在的抗阿尔茨海默病作用，值得进一步研究和开发。
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.
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