基于网络药理学探讨“莪术-三棱”抗肝纤维化作用机制

Mechanism of“Zedoary Turmeric-Rhizoma Sparganii”against liver fibrosis based on network pharmacology

目的采用网络药理学的技术,初步明确“莪术-三棱”抗肝纤维化的分子生物学机制。方法通过中药系统药理学分析平台(TCMSP)获取与莪术、三棱有关的活性成分及其潜在关键靶点,应用TCMSP、Pubchem和Swiss Target Prediction数据库对药物的活性成分进行筛选、靶点的收集和处理,再通过GeneCards数据库筛选肝纤维化的靶点基因,将化合物靶点与肝纤维化靶点进行交互处理,得到的重叠靶点输入到String数据库,利用cytoscape3.8.2获得关键靶点蛋白在整体网络上的作用,之后将重叠靶点蛋白导入Metascape数据库进行GO及KEGG作用通路分析。结果从TCMSP检索和文献搜集得到莪术和三棱对应的有效成分共11个,通过Genecards数据库中获取肝纤维化相关基因共5820个,交互得到关键靶点基因19个,利用String和Metascape数据库进行靶标功能富集分析,得到15个重要靶标,富集在4条抗肝纤维化相关通路上,涉及细胞的凋亡和自噬、炎症反应、癌症中的蛋白多糖等多种作用,不同相关基因和蛋白通路对调控肝纤维化发挥不同作用,也说明药物的配伍可发挥多成分、多靶标的整体调控作用。结论利用网络药理学,通过活性成分筛选、靶点预测、网络拓扑分析、富集分析和通路分析,提示“莪术-三棱”可通过多种途径预防和治疗肝纤维化,体现了中药多成分、多靶点、多途径的作用特点,为临床研究及进一步开发提供了思路。

Objective To preliminarily clarify the molecular biological mechanism of“Zedoary Turmeric-Rhizoma Sparganii”against liver fibrosis by the technology of network pharmacology.Methods The active components and potential key targets related to“Zedoary Turmeric-Rhizoma Sparganii”were obtained by systematic pharmacology analysis platform of Chinese Medicine(TCMSP).TCMSP,Pubchem and Swiss Target Prediction database were used to screen the active ingredients of the drugs,collect and process the targets.Then the target genes of liver fibrosis were screened through GeneCard database,and the compound target was interacted with the liver fibrosis target.The overlapping targets obtained were input into String database,cytoscape 3.8.2 was used to obtain the role of key target proteins in the overall network,and then the overlapping target proteins were imported into Metascape database for GO and KEGG pathway analysis.Results A total of 11 active components corresponding to“Zedoary Turmeric-Rhizoma Sparganii”were obtained from TCMSP retrieval and literature collection.A total of 5820 genes related to liver fibrosis were obtained from the Genecard database,and 19 key target genes were obtained by interaction.Target function enrichment analysis was performed using the String and Metascape databases and 15 important targets were enriched on 4 anti-hepatic fibrosis pathways,which were related to multiple effects of cell apoptosis and autophagy,inflammatory reaction,proteoglycan in cancer.Different related genes and protein pathways played different roles in regulating liver fibrosis,which also showed that the compatibility of drugs could play a multi-component and multi-target overall regulatory role.Conclusions Through network pharmacology,active ingredient screening,target prediction,network topology analysis,enrichment analysis and pathway analysis showed that“Zedoary Turmeric-Rhizoma Sparganii”drugs could prevent and treat liver fibrosis through many ways,which reflected the characteristics of multi-component,multi-target and multi-pathway of traditional Chinese medicine and could provide ideas for clinical research and further development.