基于网络药理学、分子对接探讨青蒿治疗脓毒症的作用机制

Based on Network Pharmacology and Molecular Docking, the Mechanism of Action of Artemisia annua in the Treatment of Sepsis Was Discussed

摘要: 目的：应用网络药理学方法预测青蒿抗脓毒症的活性成分和作用机制。方法：首先利用TCMSP数据库获取青蒿的活性成分；基于PubChem数据库及SwissTargetPrediction数据库预测活性成分靶点；利用GeneCards数据库获取脓毒症基因，将基因映射到活性成分靶点，得到青蒿抗脓毒症的靶点；使用String数据库构建蛋白互作关系网络(PPI)；使用Cytoscape软件构建“青蒿–活性成分–交集靶点”网络图；DAVID数据库进行基因本体(GO)富集分析和京都基因和基因组百科全书(KEGG)通路富集分析；通过分子对接检验核心成分与核心靶点的结合活性。结果：青蒿治疗脓毒症的主要活性成分主要有双氢青蒿素、槲皮素、木樨草素等，获得88个交集靶点，包括SRC、MAPK3、AKT1、MAPK1、EGFR、HSP90AA1、RHOA、MMP9、MAPK14、APP、F2、ADRBK1，这12个靶向基因可能在疾病治疗中起关键作用。获得GO富集条目共544个和KEGG富集通路146条，主要与脂质与动脉粥样硬化、内分泌阻力、肺结核、弓形体病、癌症的途径、EGFR酪氨酸激酶抑制剂耐药性等通路有关。分子对接结果表明青蒿的主要活性成分对核心靶点具备良好的亲和力，在治疗脓毒症中发挥核心作用。结论：初步研究了青蒿治疗脓毒症的作用机制，青蒿具有多成分、多靶点的特点，可以通过多个靶点、多条通路来发挥治疗脓毒症的作用。

Abstract: Objective: To apply network pharmacology to predict the active ingredients and mechanism of action of Artemisia annua anti-sepsis. Methods: First, the active ingredients of Artemisia annua were obtained by TCMSP database. Prediction of active ingredient targets based on PubChem database and SwissTargetPrediction database; the GeneCards database was used to obtain sepsis genes, and the genes were mapped to active ingredient targets to obtain the anti-sepsis target of Artemisia annua. Use the String database to build a protein interaction network (PPI); the Cytoscape software was used to construct the network diagram of “Artemisia annua-active ingredient-intersec- tion target”; DAVID database for gene ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis; the binding activity of core components and core targets was tested by molecular docking. Results: The main active ingredients of Artemisia annua in the treatment of sepsis were mainly dihydroartemisinin, quercetin, luteolin, and 88 intersection targets were obtained, including SRC, MAPK3, AKT1, MAPK1, EGFR, HSP90AA1, RHOA, MMP9, MAPK14, APP, F2, ADRBK1, these 12 targeted genes may play a key role in disease treatment. A total of 544 GO enrichment entries and 146 KEGG enrichment pathways were obtained, mainly related to lipid and atherosclerosis, endocrine resistance, tuberculosis, toxoplasmosis, cancer pathways, EGFR tyrosine kinase inhibitor resistance and other pathways. The molecular docking results showed that the main active components of Artemisia annua had good affinity for the core target and played a central role in the treatment of sepsis. Conclusion: The mechanism of action of Artemisia annua in the treatment of sepsis has been preliminarily studied, and Artemisia annua has the characteristics of multi-component and multi-target, which can play a role in the treatment of sepsis through multiple targets and multiple pathways.