基于网络药理学和分子对接技术挖掘半贝丸治疗支气管炎的作用机制

Mechanism of Banbei Pills in treatment of bronchitis based on network pharmacology and molecular docking technology

目的通过网络药理学及分子对接技术探讨半贝丸治疗支气管炎的分子作用机制。方法基于TCMSP数据库结合文献报道筛选半贝丸的有效活性成分并预测作用靶点,构建半贝丸“成分–靶点”网络;运用GeneCards数据库和OMIM数据库获取支气管炎疾病靶点,构建韦恩图,获得半贝丸治疗支气管炎的作用靶点;采用Cytoscape软件构建“疾病–活性成分”网络模型;运用String平台将共同靶点进行蛋白相互作用(PPI)网络分析,通过Metascape数据库对靶点进行基因本体(GO)功能富集及基因组百科全书(KEGG)通路富集;并采用SwissDock在线数据库进行分子对接。结果筛选得到半贝丸活性成分29个,共获得潜在靶点95个,支气管炎疾病靶点1964个,半贝丸与支气管炎共同靶点49个。网络分析结果表明,半贝丸治疗支气管炎的关键靶点包括蛋白激酶(Akt1)、血管内皮生长因子A(VEGFA)、肿瘤抑制因子P53(TP53)、半胱氨酸蛋白酶3(CASP3)、原癌基因c-Jun产物(JUN)、基质金属蛋白酶-9(MMP9)等,主要通过细胞对有机环状化合物的反应、凋亡信号通路、转录调节复合物、半胱氨酸型内肽酶活性参与凋亡信号通路等生物过程发挥作用,KEGG富集主要涉及磷脂酰肌醇-3-激酶(PI3K)/Akt、细胞凋亡、晚期糖基化终末产物–晚期糖基化终末产物受体(AGE-RAGE)等信号通路。分子对接结果显示半贝丸中β-谷固醇、黄芩素、豆甾醇等关键化合物与Akt1、VEGFA、TP53、CASP3等关键靶点有较好的结合能力。结论半贝丸治疗支气管炎具有多成分、多靶点和多通路等特征。

Objective To mining the mechanism of Banbei Pills in treatment of bronchitis by network pharmacology and molecular docking and molecular docking technology.Methods To search the chemical components and targets of Banbei Pills by literature mining and TCMSP platform,and construct the“ingredient–target”network of Banbei Pills.To obtain the disease targets of bronchitis by GeneCards and OMIM database,and construct Venn diagram to obtain the targets of Banbei Pills in treatment of bronchitis.The“disease–active ingredient”network model was constructed using Cytoscape software.The common target was analyzed by using String platform for protein interaction(PPI)network analysis,and the target was enriched by GO function and KEGG pathway through Metascape database.SwissDock online database was used for molecular docking.Result A total of 29 components,95 potential targets,1964 targets related to bronchitis,and 49 targets of Banbei Pills and bronchitis were obtained.The network analysis results showed that the key targets of Banbei Pills in treatment of bronchitis included Akt1,VEGFA,TP53,CASP3,JUN,and MMP9.Biological processes mainly involved cellular response to organic cyclic compound,apoptotic signaling pathway,transcription factor complex and cysteine-type endopeptidase activity involved in apoptotic signaling pathway.KEGG enrichment mainly involved PI3K/Akt,apoptosis,AGE-RAGE and other signaling pathways.The molecular docking results showed thatβ-sitosterol,baicalein,and sitosterol and other key compounds in Banbei Pills have better binding ability with key targets such as Akt1,VEGFA,TP53,and CASP3.Conclusion Banbei Pills in treatment of bronchitis have the characteristics of multi-component,target,and multi-pathway.