基于网络药理学及分子对接探讨三七总皂苷治疗脓毒症的作用机制  

Study on the Mechanism of Panax Notoginsenosides in the Treatment of Sepsis Based on Network Pharmacology and Molecular Docking

作　　者：黄萍娥 杨萍 黄威 刘云涛 王津 王远平 叶烨 HUANG Ping’e;YANG Ping;HUANG Wei;LIU Yuntao;WANG Jin;WANG Yuanping;YE Ye(Guangzhou University of Chinese Medicine,Guangzhou 510006 Guangdong,China;The Second Affiliated Hospital of Guangzhou University of Chinese Medicine,Guangzhou 510120 Guangdong,China;Guangdong Second Traditional Chinese Medicine Hospital,Guangzhou 510095 Guangdong,China)

机构地区：[1]广州中医药大学,广东广州510006 [2]广州中医药大学第二附属医院,广东广州510120 [3]广东省第二中医院,广东广州510095

出　　处：《中药新药与临床药理》2024年第7期1028-1034,共7页Traditional Chinese Drug Research and Clinical Pharmacology

基　　金：广东省中医药管理局科研项目(20221189)。

摘　　要：目的基于网络药理学与分子对接技术探讨三七总皂苷治疗脓毒症的作用机制。方法通过检索TCMSP、Swiss Target Prediciton和PharmMapper数据库得到三七总皂苷的作用靶点;在Genecard、Drugbank、Disgenet和OMIM数据库检索脓毒症的疾病相关靶点;将筛选出的三七总皂苷作用靶点与脓毒症疾病相关靶点取交集,作为三七总皂苷治疗脓毒症的潜在作用靶点。通过STRING数据库构建潜在作用靶点的蛋白互作(PPI)网络,并筛选关键靶点;对潜在作用靶点进行GO功能及KEGG通路富集分析,构建药物-疾病-靶点-通路网络;利用AutoDock Vina软件对三七总皂苷5种单体皂苷成分与三七总皂苷治疗脓毒症的关键靶点进行分子对接验证。结果获得三七总皂苷治疗脓毒症的潜在作用靶点206个;筛选得到AKT1、TP53、SRC、STAT3、JUN、TNF、IL6、MAPK1、PIK3R1和IL1B等关键靶点。潜在作用靶点GO功能富集分析得到2548项生物过程(BP)条目,174项分子功能(MF)条目,47项细胞组分(CC)条目;KEGG通路富集分析共得到171条信号通路。三七总皂苷主要活性成分三七皂苷R1、人参皂苷Rg1、人参皂苷Re、人参皂苷Rb1、人参皂苷Rd与关键靶点AKT1、TP53、STAT3、SRC、JUN具有较强的结合活性。结论三七总皂苷可能通过AKT1、TP53、SRC、STAT3、TNF等关键靶点,作用于PI3K-Akt、AGE-RAGE等主要信号通路,进而影响脓毒症的炎症反应、细胞凋亡和凝血反应等生理过程,发挥治疗脓毒症的作用。Objective To explore the mechanism of Panax notoginsenosides in the treatment of sepsis based on network pharmacology and molecular docking technology.Methods The action targets of total saponins of Panax notoginsenosides were obtained by searching the databases of TCMSP,Swiss Target Prediciton and PharmMapper,and the disease-related targets of sepsis were searched in the databases of Genecard,Drugbank,Disgenet and OMIM.The selected targets of total saponins of Panax notoginsenosides were intersected with the disease-related targets of sepsis,which were used as potential targets for the treatment of sepsis.The protein-protein interaction(PPI)network of potential targets was constructed by STRING database,and the key targets were screened;the potential targets were analyzed by GO function and KEGG pathway enrichment analysis,and the drug-disease-target-pathway network was constructed;the molecular docking of five monomer saponins of Panax notoginsenosides and the key targets of Panax notoginsenosides in the treatment of sepsis was studied by AutoDock Vina software.Results A total of 206 potential targets of Panax notoginsenosides in the treatment of sepsis were obtained,and key targets such as AKT1,TP53,SRC,STAT3,JUN,TNF,IL6,MAPK1,PIK3R1 and IL1B were screened.A total of 2548 biological process(BP)items,174 molecular function(MF)items and 47 cellular component(CC)items were obtained by GO functional enrichment analysis of potential targets,and 171 signal pathways were obtained by KEGG pathway enrichment analysis.The main active components of Panax notoginsenosides R1,ginsenoside Rg1,ginsenoside Re,ginsenoside Rb1 and ginsenoside Rd have strong binding activity with key targets AKT1,TP53,STAT3,SRC and JUN.Conclusion Panax notoginsenosides may act on the main signal pathways such as PI3K-Akt and AGE-RAGE through the key targets such as AKT1,TP53,SRC,STAT3 and TNF,and then affect the physiological processes such as inflammation,apoptosis and blood coagulation in sepsis,and play a role in the treatment of sepsis.

关 键 词：三七总皂苷 脓毒症 网络药理学 分子对接 炎症反应 细胞凋亡 凝血反应 

分 类 号：R285.5[医药卫生—中药学] R857.3[医药卫生—中医学]