基于网络药理学探讨黄芪治疗肝纤维化的作用机制

Mechanism of action of Astragalus membranaceus in treatment of liver fibrosis:A study based on network pharmacology

目的:基于网络药理学方法探讨黄芪治疗肝纤维化的作用机制。方法:使用TCMSP、PubChem和Swiss Target Prediction数据库预测黄芪有效成分的靶点;通过GenCards数据库收集肝纤维化靶点,取交集得到黄芪对肝纤维化的作用靶点。运用Cytoscape 3.8.2构建黄芪-有效成分-靶点-肝纤维化网络,预测核心靶点,构建基于STRING平台的PPI网络。利用Metascape平台进行基因本体(GO)功能和京都基因与基因组百科全书(KEGG)通路富集分析。结果:筛选得到黄芪有效成分20种,治疗肝纤维化的相关靶点90个,疗效明显的有效成分是山柰酚、华良姜素、异鼠李素、槲皮素等,核心靶点是白细胞介素-6(IL-6)、丝氨酸/苏氨酸激酶1(AKT1)、转录因子(JUN)、表皮生长因子受体(EGFR)、半胱氨酰天冬氨酸特异性蛋白酶3(CASP3)等。黄芪治疗肝纤维化途径主要包括癌症通路、EGFR酪氨酸激酶抑制剂抗通路、PI3K-Akt信号通路、乙型肝炎、丙型肝炎等信号通路。结论:通过网络药理学方法初步探讨黄芪治疗肝纤维化的作用机制,表明黄芪具有多成分、多靶点、多通路等作用特点,可为基础和临床研究提供参考依据。

Objective:To investigate the mechanism of action of Astragalus membranaceus in the treatment of liver fibrosis based on network pharmacology.Methods:TCMSP,PubChem,and Swiss Target Prediction databases were used to predict the targets of the effective constituents of Astragalus membranaceus,and GenCards database was used to obtain the targets of liver fibrosis;intersection of the two groups of targets was performed to obtain the action targets of Astragalus membranaceus on liver fibrosis.Cytoscape 3.8.2 was used to construct an Astragalus membranaceus-effective constituent-target-liver fibrosis network to predict core targets,and a protein-protein interaction network was constructed based on STRING platform.Metascape platform was used to perform gene ontology and Kyoto Encyclopedia of Genes and Genome pathway enrichment analyses.Results:A total of 20 effective constituents of Astragalus membranaceus was obtained,as well as 90 targets associated with the treatment of liver fibrosis;the effective constituents with a marked effect included kaempferol,kumatakenin,isorhamnetin,and quercetin,and the core targets included interleukin-6,AKT1,JUN,epithelial growth factor receptor(EGFR),and CASP3.The main pathways involved in the treatment of liver fibrosis by Astragalus membranaceus mainly included cancer pathway,EGFR tyrosine kinase inhibitor pathway,the PI3 K-Akt signaling pathway,the hepatitis B signaling pathway,and the hepatitis C signaling pathway.Conclusion:The mechanism of action of Astragalus membranaceus in the treatment of liver fibrosis preliminarily explored by network pharmacology shows that Astragalus membranaceus has the characteristics of multiple constituents,targets,and pathways,which provides a reference for basic and clinical research.