应用网络药理学及分子对接技术研究甘草泻心汤治疗白塞病的分子机制  

Molecular mechanism of Gancao Xiexin Decoction for treating Behcet's disease:Based on network pharmacology and molecular docking

作　　者：郜晨静 罗亚萍 张宁[2] 郝梦桃 GAO Chenjing;LUO Yaping;ZHANG Ning;HAO Mengtao(Department of Rheumatology,the First Affiliated Hospital of Hebei University of Chinese Medicine,Shijiazhuang,Hebei 050011;Beijing University of Chinese Medicine,Beijing 100105;Graduate School of Hebei University of Chinese Medicine,Shijiazhuang,Hebei 050091)

机构地区：[1]河北中医药大学第一附属医院风湿病科,河北石家庄050011 [2]北京中医药大学,北京100105 [3]河北中医药大学研究生院,河北石家庄050091

出　　处：《河北中医》2024年第3期500-505,共6页Hebei Journal of Traditional Chinese Medicine

基　　金：国家中医药管理局第四批全国中医(临床、基础)优秀人才研修项目(国中医药办人教发〔2017〕24号)。

摘　　要：目的运用网络药理学和分子对接技术研究甘草泻心汤治疗白塞病(BD)的分子机制,为今后的研究提供参考。方法运用中药系统药理学数据库与分析平台(TCMSP)获取甘草泻心汤中七味药材的有效成分与作用靶点,并利用UniProt数据库将作用靶点基因加以注释和整合。通过GeneCard、PharmGkb、TTD、OMIM、DrugBank数据库获得BD疾病靶点,并与药物作用靶点取交集。使用Cytoscape 3.8.0软件构建药物-成分-疾病靶点网络图;使用STRING数据库构建蛋白质与蛋白质相互作用(PPI)网络,并用Cytoscape 3.8.0软件进行分析;使用R×644.0.5软件和脚本对交集靶点进行基因本体(GO)功能和京都基因与基因组百科全书(KEGG)通路富集分析;运用AutoDock Tools对核心靶点及核心成分进行分子对接验证。结果共筛选出甘草泻心汤236个成分、3480个靶点,986个BD疾病靶点,63个药物与疾病交集靶点,筛选出槲皮素、β-谷甾醇、山奈酚、豆甾醇、黄芩甙元、富马碱、汉黄芩素7个核心成分,前列腺素内过氧化物合酶2(PTGS2)、白细胞介素18(IL-18)、CC趋化因子配体2(CCL2)、基质金属蛋白酶9(MMP-9)、信号转导与转录激活因子3(STAT3)、血管内皮生长因子A(VEGFA)、CXC趋化因子配体8(CXCL8)7个核心靶点。共得到1804个GO条目,106条KEGG通路,包含晚期糖基化终末产物/晚期糖基化终末产物受体(AGE-RAGE)信号通路、IL-17信号通路、缺氧诱导因子-1(HIF-1)信号通路等。分子对接结果显示,药物核心成分与疾病核心靶点之间有较强的结合能力。结论甘草泻心汤可通过多成分、多靶点、多通路治疗BD。Objective To study the molecular mechanism of Gancao Xiexin Decoction for treating Behcet's disease(BD)based on network pharmacology and molecular docking,thus providing reference for future research.Methods The effective components and functional targets of seven herbs in Gancao Xiexin Decoction were extracted from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP).The target genes were collected by using Uniprot database.The disease targets obtained in GeneCard,DrugBank,PharmGkb,TTD and OMIM database were intersected with drug action targets.A drug-component-disease-target network was performed using Cytoscape 3.8.0 software.Protein-protein interaction(PPI)networks were constructed and analyzed using the STRING database and Cytoscape 3.8.0 software,respectively.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analyses on the intersection genes were performed by the R×644.0.5 software.AutoDock Tools molecularly docked the main active ingredients to the drug core target.Results A total of 236 chemical components and 3480 action targets,including 986 disease targets and 63 drug-disease intersection targets of Gancao Xiexin Decoction for BD were screened out in this study.The seven core components including quercetin,beta-sitosterol,kaempferol,stigmasterol,baicalein,fumarine,wogonin,and the seven key targets including prostaglandin-endoperoxide synthase 2(PTGS2),interleukin 18(IL-18),CC-chemokine ligand 2(CCL2),matrix metalloproteinase 9(MMP-9),signal transducer and activator of transcription 3(STAT3),vascular endothelial growth factor A(VEGFA),C-X-C motif chemokine ligand 8(CXCL-8)were revealsed.A total of 1804 GO and 106 KEGG pathways were obtained,including advanced glycation end products(AGE)/receptor for advanced glycation end products(RAGE)pathway,IL-17 pathway,hypoxia-inducible factor-1(HIF-1)and other related signaling pathways.The Molecular docking analysis suggested a strong correlation between the core components and the key target

关 键 词：贝赫切特综合征 甘草泻心汤 药理作用分子作用机制(中药) 网络药理学 分子对接 

分 类 号：R751[医药卫生—皮肤病学与性病学] R289.5[医药卫生—临床医学] R285.5