基于网络药理学的南、北五味子治疗阿尔茨海默病作用机制比较研究  

Comparative study on mechanism of Schisandra sphenanthera and Schisandra chinensis in treatment of Alzheimer's disease based on network pharmacology

作　　者：安淑荣 宋琳 李莉 朴钟源 楚魏 练依彤 AN Shurong;SONG Lin;LI Li;PIAO Zhongyuan;CHU Wei;LIAN Yitong(School of Basic Medicine,Heilongjiang University of Chinese Medicine,Harbin 150040,China;School of Life Sciences,Huizhou University,Huizhou 516007,China;Department of Neurology,Huizhou Third People's Hospital,Huizhou Hospital Affliated to Guangzhou Medical University,Huizhou 516002,China)

机构地区：[1]黑龙江中医药大学基础医学院,黑龙江哈尔滨150040 [2]惠州学院生命科学学院,广东惠州516007 [3]惠州市第三人民医院广州医科大学附属惠州医院神经内科,广东惠州516002

出　　处：《药物评价研究》2024年第1期26-37,共12页Drug Evaluation Research

基　　金：国家自然科学基金资助项目(81673860);广州医科大学科研能力提升计划项目(广医发[2023]16号)。

摘　　要：目的 基于网络药理学和分子对接技术探究南五味子与北五味子治疗阿尔茨海默病(AD)的作用机制异同。方法通过中药系统药理学数据库及分析平台(TCMSP)和已发表的文献筛选南、北五味子的活性成分,利用Swiss Target Prediction、OMIM、GeneCards数据库获得AD相关疾病靶点,通过Cytoscape 3.9.1绘制“药物-活性成分-交集靶点”网络图。利用Venny 2.1筛选共性和特有靶点,通过String数据库、Cytoscape 3.9.1构建蛋白质-蛋白质相互作用(PPI)网络,利用Cytoscape 3.9.1的CytoNCA工具进行靶点拓扑分析筛选关键靶点,Metascape平台对共性和特有靶点进行基因本体(GO)功能及京都基因与基因组百科全书(KEGG)通路富集分析。利用AutoDock Vina对核心活性成分和关键靶点进行分子对接验证。结果 筛选出南五味子活性成分15个,北五味子活性成分13个,二者治疗AD共性靶点235个,南五味子治疗AD特有靶点137个,北五味子治疗AD特有靶点69个。PI3K-Akt信号通路、神经活性配体-受体相互作用、钙信号通路、MAPK信号通路等为南、北五味子治疗AD共性信号通路,Th17细胞分化、PPAR信号通路等为南五味子治疗AD特有调控信号通路,cGMP-PKG信号通路、趋化因子信号通路等为北五味子治疗AD特有调控信号通路。分子对接结果显示,南五味子核心活性成分五味子醇甲、五味子甲素、五味子酯甲、新南五味子木脂宁、新杜松烷酸B与关键靶点CASP3、ESR1、HIF1A,北五味子核心活性成分五味子醇甲、五味子甲素、五味子酯甲、脱氧三尖杉酯碱、五味子醇乙与关键靶点ADRB2、SLC6A4、ADRBK1均具有较好的结合活性。结论 南、北五味子由于产地不同,活性成分及治疗AD靶点既有相同也有不同,南、北五味子能通过共有及各自特有靶点发挥治疗AD作用。Objective To explore the similarities and differences between the mechanism of Schisandra sphenanthera Rehd.et Wils.and Schisandra chinensis(Turcz.)Baill.in treatment of Alzheimer's disease(AD)based on network pharmacology and molecular docking techniques.Methods The active components of S.sphenanthera and S.chinensis were screened from the Traditional Chinese Medicine System Pharmacology Database(TCMSP)and published literature,access to drug and disease targets using the Swiss Target Prediction,OMIM,GeneCards databases,and draw the network diagram of"drug-active component-intersection target"by Cytoscape 3.9.1.Venny 2.1 was used to screen common and unique targets.Protein-protein interaction(PPI)network was constructed by String database and Cytoscape 3.9.1.CytoNCA tool of Cytoscape 3.9.1 was used to screen key targets by target topology analysis.The Metascape platform performs GO functional and KEGG pathway enrichment analysis for common and unique targets.Finally,AutoDock Vina was used to verify the molecular docking of core active components and key targets.Results There were 15 active components of S.sphenanthera,13 active components of S.chinensis,there are 235 common targets for treating AD,137 unique targets of S.sphenanthera for treating AD,and 69 unique targets of S.chinensis for treating AD.The PI3KAkt signaling pathway,neuroactive ligand-receptor interaction,calcium signaling pathway and MAPK signaling pathway were common signal pathways of S.sphenanthera and S.chinensis in treating AD.Th17 cell differentiation and PPAR signaling pathway were the unique regulatory signal pathways of S.sphenanthera in treating AD.The cGMP-PKG signaling pathway and chemokine signaling pathway were the unique regulatory signal pathways of S.chinensis in treating AD.Molecular docking results showed that S.sphenanthera core active components schisandrin,schisandrin A,schisantherin A,neokadsuranin and neokadsuranic acid B had good binding activity with key targets CASP3,ESR1 and HIF1A.S.chinensis core active components schi

关 键 词：南五味子 北五味子 阿尔茨海默病 网络药理学 五味子醇甲 五味子甲素 五味子酯甲 

分 类 号：R285.5[医药卫生—中药学]