基于中药化学生物学理论探讨小青龙汤在肺系疾病中的靶点群及作用机制

Discussion About the Target Groups and Mechanism of Minor Green Dragon Decoction in Lung Diseases Based on the Theory of Chemical Biology of TCM

目的:基于中药化学生物学理论,运用生物信息学分析方法对小青龙汤治疗肺系疾病的靶点群及机制进行探讨。方法:通过中药系统药理学数据库与分析平台(traditional chinese medicine systems pharmacology database and analysis platform, TCMSP)对小青龙汤中活性成分进行筛选,基于所筛选成分,从Swiss Target Prediction、PharmMapper预测成分相关靶点。同时用DisGeNET、GeneCards和CTD数据库收集肺系疾病相关靶点,通过成分靶点和疾病靶点映射分析,运用STRING数据库对交集靶点群进行蛋白质互作网络(protein-protein interaction, PPI)分析,应用Metascape和DAVID在线分析平台对交集靶点群进行基因本体论(gene ontology, GO)生物过程和KEGG通路富集分析,使用SYBYL-X2.0软件对分析结果进行分子对接验证。结果:获得2个靶点群,分别涉及63个和160个靶点。PPI网络分析显示,丝氨酸/苏氨酸蛋白激酶(serine/threonine-protein kinase 1,AKT1)、血管内皮生长因子(vascular endothelial growth factor A,VEGFA)、白细胞介素-6 (Interleukin-6,IL-6)、TP53和肿瘤坏死因子(tumor necrosis factor, TNF)等靶点具有较高的度值;GO生物学过程主要涉及促分裂原活化蛋白激酶(mitogenactivated protein kinase, MAPK1)级联的调控、一氧化氮(nitric oxide, NO)生物合成和炎症反应等;KEGG通路富集分析显示,PI3K-AKT信号通路具有较高的度值;分子对接结果显示,槲皮素和MAPK、VEGFA、CDK2、PTK2靶点的对接得分较高。结论:小青龙汤可能通过调控PI3K-AKT信号通路及其相关靶点发挥治疗肺系疾病的作用。

Objective:To explore the target groups and mechanism of Minor Green Dragon Decoction in the treatment of lung diseases by using bioinformatics analysis method based on the chemical biology theory of TCM.Methods:The active components in Mi-nor Green Dragon Decoction were screened by traditional Chinese medicine systems pharmacology database and analysis platform(TCMSP).Based on the screened components,the component-related targets were predicted from Swiss Target Prediction and PharmMapper.At the same time,lung disease-related targets were collected with DisGeNET,GeneCards and CTD databases,and analyzed by component targets and disease target mapping,The protein-protein interaction(PPI)was analyzed by using STRING database.The gene ontology(GO)biological process and KEGG pathway enrichment were analyzed by using Metascape and DA-VID online analysis platform.The analysis results were verified by molecular docking with SYBYL-XZ2.0 software.Results:A total of 2 target groups were obtained,involving 63 and 160 targets respectively.PPI network analysis showed that serine/threonine protein kinase 1(AKT1),vascular endothelial growth factor A(VEGFA),interleukin-6(IL-6),TP53 and tumor necrosis factor(TNF)and other tagets had high degree values.The biological process of GO mainly involved the regulation of mitogen-activated protein kinase(MAPK1)cascade and nitric oxide(NO)biosynthesis and inflammatory response.KEGG pathway enrichment analysis showed that PI3K-AKT signal pathway had high degree value.Molecular docking results showed that quercetin had higher docking scores with MAPK,VEGFA,CDK2 and PTK2 targets.Conclusion:Minor Green Dragon Decoction may play a role in the treatment of lung diseases by regulating PI3K-AKT signal pathway and its related targets.