摘要
目的:根据网络药理学技术分析加减薯蓣丸治疗阿尔茨海默病(AD)的有效活性成分及其疗效作用机制。方法:通过网络药理数据库与分析平台(TCMSP)筛选加减薯蓣丸的潜在活性成分与相对应的靶点;根据GEO数据库挖掘AD疾病差异基因;通过加减薯蓣丸相关药物活性成分与AD疾病靶点基因,构建中药复方调控网络,并进行基因本体(GO)功能富集及京都基因与基因组百科全书(KEGG)通路富集分析;通过Cytoscape软件构建中药成分-靶点网络模型、靶点-通路网络模型,并分析其交互靶点及信号通路;通过APP/PS1双转基因小鼠模型对网络药理学部分靶点蛋白进行验证。采用蛋白质印迹法(WB)检测CD14蛋白、TLR4蛋白、IKKβ蛋白的表达情况。结果:加减薯蓣丸中可能包含paeoniflorin、luteolin、Myricanone等12个有效活性成分,CD14、IKBKB、MAPK14等9个靶点基因;GO功能富集分析涉及脂多糖反应、炎症反应、脂磷壁酸反应、髓系白细胞分化、成肌细胞分化调控等方式治疗AD;KEGG富集分析得出45条信号通路,涉及Toll-样受体信号通路、Th1和Th2细胞分化、丝裂原活化蛋白激酶(MAPK)信号通路、肿瘤坏死因子(TNF)信号通路等。WB结果显示,与模型组比较,加减薯蓣丸能显著降低CD14、TLR4、IKKβ蛋白表达(P<0.05)。结论:加减薯蓣丸可能通过对CD14、IKBKB等靶点基因的调节起到治疗AD的作用,且通过实验证实了部分靶点基因蛋白,这为临床治疗与实验研究提供了客观理论依据。
Objective:To investigate the effective active components in Modified Shuyu Pills and the mechanism of the Pills in treating Alzheimer′s disease(AD)by network pharmacology.Methods:The potential active components and corresponding targets of the Pills were screened on the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),a database and analysis platform of network pharmacology.Differential genes in AD were retrieved from the Gene Expression Omnibus(GEO)database.Then,a regulatory network of traditional Chinese medicine(TCM)compounds was constructed based on the active components related to the Pills and AD target genes.GO function enrichment and KEGG pathway enrichment analysis were also performed.TCM component-target network model and target-pathway network model were also constructed using Cytoscape software to analyze the interactive targets and signaling pathways.The target proteins obtained by network pharmacology were validated using the amyloid precursor protein/presenilin 1(APP/PS1)double transgenic mice model.Additionally,cluster differentiation 14(CD14),Toll-like receptor 4(TLR4),and IκB kinaseβ(IKKβ)protein expression was detected by Western blot(WB).Results:The Pills may contain 12 effective active components(including paeoniflorin,luteolin,and Myricanone),9 target genes[including CD14,inhibitor of kappa light polypeptide gene enhancer in B-cell kinase beta(IKBKB),and mitogen-activated protein kinase(MAPK14)].According to GO functional enrichment analysis,AD treatment primarily involved the response to lipopolysaccharide,inflammatory reaction,response to lipoteichoic acid,myeloid leukocyte differentiation,myoblast differentiation,and other methods.KEGG enrichment analysis resulted in 45 signaling pathways,including Th1 and Th2 cell differentiation,as well as TLR,MAPK,and TNF signaling pathways.WB results showed that compared with the model group,the Pills could reduce the CD14,TLR4,and IKKβprotein expression(P<0.05).Conclusion:Modified Shuyu Pills may exert therapeutic effects on AD by regulating target genes such as CD14 and IKBKB.Additionally,parts of target gene proteins are confirmed through the experiment,which provides an objective theoretical basis for clinical treatment and experimental research.
作者
周剑杰
李鸣
谭子虎
王建婷
ZHOU Jianjie;LI Ming;TAN Zihu;WANG Jianting(Hubei Provincial Hospital of Traditional Chinese Medicine,Wuhan 430061,China;Hubei University of Chinese Medicine,Wuhan 430065,China)
出处
《世界中医药》
北大核心
2025年第21期3826-3831,3840,共7页
World Chinese Medicine
基金
国家自然科学基金面上项目(30873292)
湖北省自然科学基金重点项目(2015CFA089)。
关键词
加减薯蓣丸
阿尔茨海默病
网络药理学
作用机制
差异基因
靶点
信号通路
实验验证
Modified Shuyu Pill
Alzheimer′s disease
Network pharmacology
Mechanism
Differential gene
Target
Signaling pathway
Experimental verification
