基于网络药理学和分子对接探讨扶正化纤方治疗特发性肺纤维化的机制

Mechanism of Fuzheng Huaxian Decoction in the treatment of idiopathic pulmonary fibrosis based on network pharmacology and molecular docking

目的通过网络药理学探讨扶正化纤方的活性成分及其作用于特发性肺纤维化(IPF)的主要生物过程及信号通路,探究扶正化纤方治疗特发性肺间质纤维化的核心靶点与机制。利用分子对接技术对结果进行验证。方法通过检索TCMSP、HERB、Uniport、Genecards、Swiss Target Prediction数据库,寻找药物的活性成分、潜在靶点及疾病的靶点基因,将筛选得到的药物-疾病共有靶点输入String数据库,构建靶点蛋白相互作用网络(PPI),利用R语言进行基因本体(GO)生物过程和京都基因与基因组百科全书(KEGG)通路富集分析。结果共筛选得到药物有效成分174个,药物靶点333个,疾病靶点3509个。拓扑分析发现丝氨酸/苏氨酸蛋白激酶1(AKT1)、肿瘤坏死因子(TNF)、肿瘤蛋白P53(TP53)、血管内皮生成因子A(VEGFA)等可能为扶正化纤方治疗特发性肺纤维化的核心靶点。GO和KEGG功能富集分析发现扶正化纤方主要通过晚期糖基化终产物受体(AGE-RAGE)信号通路、磷脂酰肌醇-3激酶/蛋白激酶B(PI3K/AKT)信号通路、白细胞介素(IL)-17信号通路发挥作用。结论通过网络药理学和分子对接研究发现,扶正化纤方可以通过多靶点、多信号通路,缓解特发性肺间质纤维化的进展,为进一步深入研究扶正化纤方治疗特发性肺间质纤维化提供了科学依据。

Objective To investigate the active ingredients of Fuzheng Huaxian Decoction and its main biological processes and signaling pathways acting on idiopathic pulmonary fibrosis(IPF)through network pharmacology,to explore the core targets and mechanisms of Fuzheng Huaxian Decoction for the treatment of IPF,and to validate the results with molecular docking techniques.Methods Active ingredients of drugs,potential targets and target genes of diseases were screened from TCMSP,HERB,Uniport,Genecards,and Swiss Target Prediction databases.Then the screened drug⁃disease common targets were input into String database to construct target protein⁃protein interaction(PPI)network,and R language was used to perform gene ontology(GO)biological process and Kyoto encyclopedia of genes and genomes(KEGG)pathway enrichment analyses.Results A total of 174 active ingredients,333drug targets and 3509 disease targets were screened.The topological analysis revealed that serine/threonine kinase 1(AKT1),tumor necrosis factor(TNF),tumor protein 53(TP53),and vascular endothelial growth factor A(VEGFA)might be the core targets of Fuzheng Huaxian Decoction for the treatment of IPF.GO and KEGG functional enrichment analyses revealed that Fuzheng Huaxian Decoction mainly interfered with IPF through advanced glycation end product⁃receptor for advanced glycation end⁃product(AGE⁃RAGE)signaling pathway,phosphatidylinositol 3⁃kinase(PI3K⁃AKT)signaling pathway,and interleukin 17(IL⁃17)signaling pathway.Conclusion The present study based on network pharmacology and molecular docking finds that Fuzheng Huaxian Decoction can alleviate the progression of IPF through multitargets and multi⁃signaling pathways,which provides a basis for further study of Fuzheng Huaxian Decoction for the treatment of IPF.