基于网络药理学与分子对接探讨犀角地黄汤治疗脓毒症的分子作用机制

Exploring the Molecular Mechanism of Treatment for Sepsis with Xijiao Dihuang Detection Based on Network Pharmacology and Molecular Docking

目的基于网络药理学和分子对接探究犀角地黄汤治疗脓毒症的主要功效。方法通过文献检索并利用TCSMP和BATMAN-TCM数据库,筛选并预测犀角地黄汤的活性成分及潜在靶点。利用GeneCard和DisGeNET数据库筛选脓毒症的相关基因。通过STRING数据库绘制潜在靶点的蛋白-蛋白相互作用(PPI)网络,利用MCODE分析得到关键基因簇后用CytoHubba分析基因簇,得到核心的基因靶点,采用MOE软件进行分子对接验证,采用clusterProfiler包进行基因本体(GO)和京都基因与基因组百科全书数据库(KEGG)富集分析。采用Cytoscape 3.8软件构建犀角地黄汤-活性成分-疾病-靶基因网络。结果最终筛选出犀角地黄汤的活性成分38个,主要靶点138个,主要参与调节白细胞介素17(IL-17)信号通路和肿瘤坏死因子(TNF)信号通路等多种人体信号通路。JUN、RELA和IL-6为核心靶点,其中己醛、芍药苷、槲皮素、鞣花酸、黄芩素、山萘酚和石竹烯等是犀角地黄汤发挥功效的主要活性成分,且分子对接结果显示其与JUN、RELA和IL-6可以通过氢键、碳氢键和疏水性相互作用的共同作用达到稳定结合的效果。结论通过系统地探讨犀角地黄汤的主要活性成分和其作用靶点与脓毒症的联系,为犀角地黄汤的用药提供理论依据,也为深入研究其活性成分提供参考价值。

Objective To explore the main efficacy of Xijiao Dihuang Decoction based on network pharmacology and molecular docking.Method Through literature search and utilizing the TCSMP and BATMAN-TCM databases,the active ingredients and potential targets of Xijiao Dihuang Decoction were screened and predicted.Collect sepsis related genes using GeneCard and DisGeNET databases.Draw a protein-protein interaction(PPI)network of potential targets through a STRING database,use MCODE analysis to obtain key gene clusters,then use CytoHubba to analyze gene clusters to obtain core gene targets,and use MOE software for molecular docking verification.Cluster Profiler package is used for gene ontology(GO)and Kyoto encyclopedia database of genes and genomes(KEGG)enrichment analysis.Construct a network of Xijiao Dihuang Decoction-active ingredients-disease-target genes using Cytoscape 3.8 software.Result 38 active ingredients and 138 main targets were selected from Xijiao Dihuang Decoction,which mainly participate in regulating various human signaling pathways such as interleukin 17(IL-17)signaling pathway and tumor necrosis factor(TNF)signaling pathway.JUN,RELA,and IL-6 are the core targets,among which hexanal,paeoniflorin,quercetin,tannic acid,baicalin,kaempferol,and caryophyllene are the main active ingredients that exert their effects in Xijiao Dihuang Decoction.Molecular docking results show that they can achieve stable binding with JUN,RELA,and IL-6 through the combined effect of hydrogen bonding,carbon hydrogen bonding,and hydrophobic interactions.Conclusion By systematically exploring the main active ingredients of Xijiao Dihuang Decoction and their relationship with its target and sepsis,scientific theoretical basis is provided for the medication of Xijiao Dihuang Decoction,and reference value is also provided for in-depth research on its active ingredients.