基于网络药理学和分子对接技术探索灯盏细辛治疗恶性高血压的分子机制  

The molecular mechanisms of Dengzhanxixin on malignant hypertension:a network pharmacology and molecular docking-based study

作　　者：刘莉 郑武洪 Liu Li;Zheng Wuhong(Editorial Department of Chinese Hypertension Journal,Journal Center,The First Affiliated Hospital of Fujian Medical University,Fujian Fuzhou 350005,China;Fuzhou University Affiliated Provincial Hospital,Fujian Fuzhou 350001,China)

机构地区：[1]福建医科大学附属第一医院期刊中心中华高血压杂志编辑部,福建福州350005 [2]福州大学附属省立医院急诊内科,福建福州350001

出　　处：《创伤与急诊电子杂志》2024年第3期183-191,共9页Journal of Trauma and Emergency(Electronic Version)

基　　金：福建省自然科学基金面上项目(2023J011205)。

摘　　要：目的运用网络药理学和分子对接技术预测灯盏细辛治疗恶性高血压的物质基础和分子机制。方法通过中药系统药理学分析平台筛选灯盏细辛的活性化合物及其作用靶点,GeneCards数据库筛选恶性高血压的疾病靶点,以Venny 2.1.0绘制韦恩图获取两者的交集靶点后,运用STRING数据库构建蛋白质-蛋白质相互作用(protein-protein interaction,PPI)网络并进行基因本体论(gene ontology,GO)、京都基因与基因组百科全书(Kyoto encyclopedia of genes and genomes,KEGG)通路富集分析,再将PPI网络结果导入Cytoscape 3.10.0筛选出核心靶点。通过Cytoscape 3.10.0构建“活性化合物-交集靶点-通路”网络并筛选出核心化合物,最后对核心靶点和核心化合物进行分子对接并计算最小结合能。结果分别筛选出12种活性化合物、182个活性化合物靶点、249个疾病靶点和28个交集靶点。交集靶点的KEGG分析主要富集在疟疾、非洲锥虫病、肿瘤坏死因子(tumor necrosis factor,TNF)信号传导等91种疾病或通路;GO分析主要富集在钙二醇1-单加氧酶活性的正向调节、平滑肌适应等628个生物学过程,丝氨酸蛋白酶抑制剂复合物、小凹等15个细胞成分,α-肾上腺素能受体活性、肾上腺素能受体活性等13个分子功能。分子对接显示核心靶点[白细胞介素(interleukin,IL)-1β、IL-6、TNF]和核心化合物(槲皮素、山奈酚和木犀草素)的最小结合能均小于﹣5kcal/mol。结论灯盏细辛可能通过调节IL-1β、IL-6和TNF水平影响TNF信号传导通路而发挥抗恶性高血压作用。Objective To predict the material bases and molecular mechanisms of Dengzhanxixin on malignant hypertension(MHT)by using network pharmacology and molecular docking.Method The active compounds of Dengzhanxixin and their targets were selected from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform;the disease-related targets of MHT were predicted through GeneCards database.Then,the common targets of active compound and disease-related targets were identified by using Venny 2.1.0.The protein-protein interaction(PPI)network of common targets was constructed through STRING database;the results of PPI network were import into Cytoscape 3.10.0 to screen the hub targets.In addition,gene ontology(GO)and Kyoto encyclopedia of genes and genomes(KEGG)enrichment analyses of common targets were also performed through STRING database.Moreover,the network of active compounds,common targets,and cell signaling pathways was constructed and hub compounds were screened by using Cytoscape 3.10.0.Finally,the molecular docking between hub targets and hub compounds was performed to calculate minimum binding energies.Result The number of active compounds,targets of active compounds,disease-related targets,and common targets were 12,182,249,and 28,respectively.91 kinds of diseases or cell signaling pathways such as malaria,African trypanosomiasis,and tumor necrosis factor(TNF)signaling pathway were enriched by KEGG enrichment analyses.628 biological processes,15 cellular components,and 13 molecular functions were enriched though GO analyses,respectively.Molecular docking studies showed that all the binding energies between the three hub targets including interleukin(IL)-1β,IL-6,and TNF and the three hub compounds including quercetin,kaempferol,and luteolin were less than﹣5 kcal/mol.Conclusion Dengzhanxixin may exert anti-MHT effects by regulating IL-1β,IL-6,and TNF to affect the TNF signaling pathway.

关 键 词：网络药理学 分子对接 灯盏细辛 恶性高血压 分子机制 

分 类 号：R285[医药卫生—中药学]