摘要
目的 通过网络药理学方法探寻大黄牡丹汤治疗脓毒症胃肠功能障碍的潜在分子作用机制.方法 从TCMSP、TCMID和TCM Database@Taiwan中药数据库获取并筛选大黄牡丹汤化学成分,并利用Swiss Tar-get Prediction数据库检索药物作用靶点;使用GeneCards筛选脓毒症和胃肠功能障碍的疾病相关作用位点;利用Venny2.1.0在线工具获取药物作用靶点和疾病相关作用位点的交集基因,并结合STRING12.0数据库和Cytoscape3.9.1软件绘制多层次相互作用的"中药-化合物-潜在治疗靶点"网络图;运用DAVID数据库完成对潜在治疗靶点的GO和KEGG通路富集分析.结果 共得到大黄牡丹汤的53个化学成分及其479个作用靶点,与2 121个脓毒症相关作用位点、6785个胃肠功能障碍相关作用位点取交集后得到124个潜在治疗靶点.大黄牡丹汤治疗脓毒症胃肠功能障碍的关键靶点为白细胞介素-6(IL-6)、白细胞介素-1β(IL-1β)及Akt1等.通过富集分析发现,大黄牡丹汤治疗脓毒症胃肠功能障碍是通过调控HIF-1信号通路、PI3K-Akt信号通路及白细胞介素-17(IL-17)信号通路等发挥抗炎、调节免疫系统的作用.结论 通过网络药理学方法发现大黄牡丹汤治疗脓毒症胃肠功能障碍的作用机制复杂,涉及多成分、多靶点和多通路,可能与抗炎、免疫系统等相关.
Abstract
Objective:To explore the potential molecular mechanism of Dahuang Mudan Decoction in treating gastrointestinal dysfunction in sepsis through network pharmacology.Methods:The chemical components of Da-huang Mudan Decoction were obtained and screened from TCMSP,TCMID and TCM Database@Taiwan database,and the drug targets were retrieved using Swiss Target Prediction database;Genecards was used to screen the dis-ease-related action sites of sepsis and gastrointestinal dysfunction;the intersection genes of drug action targets and disease-related action sites were obtained by Venny 2.1.0 online tool,and the network diagram of"traditional Chi-nese medicine-compounds-potential therapeutic targets"with multi-level interaction was drawn by combining string 12.0 database and Cytoscape 3.9.1 software;David database was used to complete the GO and KEGG path-way enrichment analysis of potential therapeutic targets.Results:A total of 53 chemical components and 479 ac-tion targets of Dahuang Mudan Decoction were obtained,and 124 potential therapeutic targets were obtained after intersection with 2 121 sepsis-related action sites and 6 785 gastrointestinal dysfunction-related action sites.The key targets of Dahuang Mudan Decoction in treating gastrointestinal dysfunction in sepsis were IL-6,IL-1β,Aktl,etc.Through enrichment analysis,it was found that Dahuang Mudan Decoction in treating gastrointestinal dysfunc-tion in sepsis played an anti-inflammatory and immune system regulating role by regulating HIF-1 signaling path-way,PI3K-Akt signaling pathway,IL-17 signaling pathway,etc.Conclusions:Through the network pharmacology method,we found that the mechanism of Dahuang Mudan Decoction in treating gastrointestinal dysfunction in sep-sis is complex,involving multiple components,multiple targets and multiple pathways,which may be related to an-ti-inflammatory,immune system,etc.
基金项目
国家中医药局高水平中医药重点学科建设项目(zyyzdxk-2023001)
NETL
NSTL
万方数据