基于网络药理学与分子对接技术探讨人参-茯苓-白术治疗溃疡性结肠炎分子机制  

Study on molecular mechanism Ginseng Radix et Rhizoma,Poria and Atractylodis Macrocephalae Rhizoma in the treatment of ulcerative colitis based on network pharmacology and molecular docking

作　　者：刘俊岑 王文娟[1] 巴寅颖[1] 迟莉[1] 王佳佳[1] Liu Juncen;Wang Wenjuan;Ba Yinying;Chi Li;Wang Jiajia(School of Traditional Chinese Medicine,Capital Medical University,Beijing 100069,China)

机构地区：[1]首都医科大学中医药学院,北京100069

出　　处：《国际中医中药杂志》2023年第11期1427-1434,共8页International Journal of Traditional Chinese Medicine

基　　金：国家自然科学基金项目(82104765);北京市中医药薪火传承“3+3”工程冯建春名医传承工作站建设项目(2015-SZ-C-58)。

摘　　要：目的基于网络药理学与分子对接技术探讨人参、茯苓、白术治疗溃疡性结肠炎的药理作用及分子机制。方法检索TCMSP获取人参、茯苓、白术的活性成分,应用SwissTargetPrediction数据库预测其作用靶点;通过OMIM、DrugBank、TTD、PharmGKB、GeneCards数据库获取溃疡性结肠炎相关靶点;利用Draw Venn Diagram网站绘制药物与疾病交集靶点韦恩图;采用Cytoscape 3.8.2绘制"药物-成分-靶点"网络,并分析网络中关联度较高的靶点及药物活性成分;采用STRING数据库构建交集靶点PPI网络,应用Cytoscape 3.8.2中的NetworkAnalyzer插件对网络进行拓扑结构分析并筛选核心靶点;利用Metascape进行GO功能及KEGG通路富集分析;使用pyrx软件的vina进行分子对接验证。结果筛选人参、茯苓、白术药物活性成分14个,核心成分为山柰酚、豆甾醇、蛇床子素、α-香树脂醇;药物靶点148个,疾病靶点1 307个,药物与疾病交集靶点50个,获得核心靶点23个,分别为ESR1、PTPN2、PIK3R1、SRC、EGFR、AKT1等。GO功能富集分析结果显示,靶点主要分布于细胞膜区,参与调节单加氧酶、氧化还原酶活性等生物功能,对激素、脂质等也具有调控作用。KEGG通路富集分析结果显示,主要富集通路为PI3K-Akt信号通路、JAK-STAT信号通路和MAPK信号通路等。分子对接结果提示,人参、茯苓、白术的核心成分山柰酚、蛇床子素等与PIK3R1、ESR1等核心靶点结合稳定。结论人参、茯苓、白术可通过调控PIK3R1、PTPN2、ESR1等靶点,调节PI3K-Akt通路、JAK-STAT通路及MAPK通路等,发挥改善免疫失调、减轻炎症反应、抑制上皮细胞凋亡、修复黏膜损伤等作用。Objective To investigate the pharmacological effects and molecular mechanisms of Ginseng Radix et Rhizoma,Poria and Atractylodis Macrocephalae Rhizoma for the treatment of ulcerative colitis based on the network pharmacology and molecular docking methods.Methods TCMSP database was applied to get the active components of Ginseng Radix et Rhizoma,Poria and Atractylodis Macrocephalae Rhizoma,and SwissTargetPrediction database was applied to predict their targets;OMIM,DrugBank,TTD,PharmGKB and GeneCards databases were used to obtain the disease targets of ulcerative colitis;Venn Diagram website was used to draw the venn diagrams of drug-disease intersecting targets;drug-component-target network diagrams were created in Cytoscape 3.8.2,and the targets and active components with high correlation in the network were analyzed;protein interaction networks of intersecting targets were constructed using the String platform,and the NetworkAnalyzer plug-in in Cytoscape 3.8.2 was applied to Topology analysis and screening of core targets were performed using the Metascape platform;GO and KEGG analysis were performed using the Metascape platform;molecular docking validation was performed using vina inside pyrx software.Results A total of 14 active components of Ginseng Radix et Rhizoma,Poria and Atractylodis Macrocephalae Rhizoma were screened,and the core components were kaempferol,stigmasterol,hederagenin,α-amyrin;148 drug targets,1307 disease targets and 50 drug-disease intersection targets were obtained;there were 23 core points such as ESR1,PTPN2,PIK3R1,SRC,EGFR,and AKT1.The results of GO analysis indicated that the targets were mainly located in the cell membrane region and were involved in the regulation of biological functions such as monooxygenase and oxidoreductase activities,as well as the regulation of hormones and lipids,etc.The results of KEGG pathway enrichment analysis revealed that the main enrichment pathways were PI3K-Akt,JAK-STAT and MAPK signaling pathways.The molecular docking results showed that the main

关 键 词：人参 茯苓(中药) 白术 结肠炎 溃疡性 网络药理学 分子对接模拟 

分 类 号：R285[医药卫生—中药学]