基于网络药理学和分子对接方法研究羚珠散抗小儿易感病毒的作用机制

Mechanism of Lingzhu Powder in treatment of children susceptible viruses based on network pharmacology and molecular docking

目的运用网络药理学和分子对接技术研究羚珠散抗小儿易感病毒的有效成分和作用机制。方法利用TCMID数据库查找羚珠散的化学成分,利用TCMSP、Pubchem、Swiss Target Prediction、SEA和STITCH数据获得羚珠散活性化合物的作用靶点;通过GeneCards数据库获得相关病毒性疾病靶点,取交集后得到共有靶点,即为羚珠散抗小儿易感病毒的潜在作用靶点。通过STRING数据库构建交集靶点的蛋白质相互作用(PPI)网络,基于degree值筛选重要靶点。利用DAVID平台对重要靶点进行基因本体论(GO)功能和京都基因与基因组百科全书(KEGG)通路富集分析。使用Cytoscape软件进行化合物–靶点网络拓扑分析,获得羚珠散抗小儿易感病毒的关键化合物和核心靶点。采用AutoDock Vina软件对筛选出的关键靶点和核心化合物进行分子对接验证。结果共获得91个活性化合物以及184个药物–疾病交集靶点,经筛选获得羚珠散抗小儿易感病毒15个核心化合物(桉油烯醇、桉脂素、丁香烯、乙酸龙脑酯等)以及3个核心靶点[C反应蛋白(CRP)、趋化因子2(CCL2)、血红素加氧酶1(HMOX1)]。KEGG通路富集分析结果显示,羚珠散抗小儿易感病毒可能主要通过调控肿瘤坏死因子(TNF)、Toll样受体、丝裂原活化蛋白激酶(MAPK)、叉头框蛋白O(FoxO)及T细胞受体等多种信号通路发挥治疗作用。分子对接结果表明,羚珠散抗易感病毒中10个核心化合物和核心靶点均有良好的结合能力,证明了网络药理学筛选结果的可靠性。结论羚珠散可通过桉油烯醇、桉脂素、丁香烯、乙酸龙脑酯等主要活性成分,结合CRP、CCL2、HMOX1等核心靶点来调控机体多种炎症反应、免疫反应相关信号通路,从而发挥抗小儿易感病毒作用。

Objective To explore the active components and action mechanism of Lingzhu Powder against infantile susceptible virus through network pharmacology and molecular docking technology.Methods To screen the active compounds of Lingzhu Powder from TCMID databases.Target of the active compound was obtained by TCMSP,Pubchem,Swiss Target Prediction,SEA,and STITCH data.The target of related viral diseases was obtained from GeneCards database,and the common target was obtained after intersection,which was the potential target of Lingzhu Powder against children susceptible virus.The protein interaction(PPI)network of intersecting targets was constructed by STRING database,and important targets were screened based on degree value.DAVID platform was used for gene ontology(GO)function and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis for important targets.Cytoscape software was used to conduct compound-target network topology analysis to obtain the key compounds and core targets of Linzu Powder against infantile susceptible virus.AutoDock Vina software was used to verify the molecular docking of key targets and core compounds.Results A total of 92 active compounds and 184 drug-disease intersection targets were obtained.15 Key compounds(cineolenol,cineolene,eugenene,bornyl acetate,etc.)and three core targets(CRP,CCL2,HMOX1)were obtained from Lingzhu Powder for anti-infantile virus.The results of KEGG pathway enrichment analysis showed that Linzu Powder may exert therapeutic effects on infantile susceptible virus mainly through regulating tumor necrosis factor(TNF),Toll-like receptor,mitogen activated protein kinase(MAPK),FoxO,and T cell receptor.The molecular docking results showed that 10 core compounds and core targets of Linzhu Powder had good binding ability against susceptible viruses,which verified the reliability of the network pharmacological screening results.Conclusion Linzu Powder can regulate a variety of signaling pathways related to inflammation and immune response through the main active ingredients such as cinetol,eudalin,eugenene,bornyl acetate,and combined with core targets such as CRP,CCL2,HMOX1,so as to play the role of anti-infantile virus.