鳖龙软肝汤抗肝纤维化-肝癌“多成分-多靶点”的网络药理学研究

“Multi-component-multi-target” network pharmacology study of Bielong Ruangan decoction against liver fibrosis-hepatocellular carcinoma

目的:基于网络药理学从“多成分-多靶点-多通路”的角度探讨鳖龙软肝汤(BLRGD)抗肝纤维化-肝硬化-肝癌(HF-LC-PLC)的物质基础与作用机制。方法:通过TCMSP数据库及PubChem数据库筛选BLRGD中药的化学成分及其对应的作用靶点,通过UniProt数据库将得到的所有靶点进行校正。利用GeneCards数据库以“Hepatic Fibrosis、Cirrhosis、Liver Cancer”为检索词查询疾病靶点,通过Cytoscape3.7.1软件对Drug-Disease进行可视化网络分析的展示,利用KOBAS在线数据库对上述靶点进行基因本体(GO)分析与KEGG通路分析,利用STRING平台和Cytoscape3.7.1软件绘制蛋白互作(PPI)网络图,分别通过OmicShare平台和Cytoscape 3.7.1软件对GO和KEGG富集分析结果进行可视化。结果:通过筛选共得到BLRGD的36个有效活性成分,116个靶点基因,HF-LC-PLC的靶点基因共3 063个,两者共同的靶点基因64个。通过化合物-靶点网络和PPI网络互作筛选出与HF-LC-PLC相关度较大的核心成分是paeoniflorgenone(芍药苷),albiflorin(芍药内酯苷),hederagenin(常春藤皂苷元),bisdemethoxycurcumin(双去甲氧基姜黄素)等,核心靶点是IL6、MAPK8、CCND1、RELA、ICAM1等,核心通路包括Metabolic pathways、TNF、Pathways in cancer等。结论:BLRGD治疗HF-LC-PLC是一个“多成分-多靶点-多通路”的复杂过程,为进一步研究BLRGD抗HF-LC-PLC的物质基础及作用机制提供了理论依据。

Objective:Based on the network pharmacology, the material basis and mechanism of Biolong Ruangan decoction(BLRGD) in the treatment of the progress of hepatic fibrosis-liver cirrhosis-primary liver cancer(HF-LC-PLC) was discussed from the perspective of “multi-component-multi-target-multi-channel”.Methods:The chemical constituents and corresponding targets of traditional Chinese medicine BLRGD were screened by TCMSP database and PubChem database, and all the targets obtained were corrected by UniProt database. The GeneCards database was used to investigate the targets of "Hepatic Fibrosis, liver cirrhosis, primary liver cancer. Cytoscape 3.7.1 software was used to display Drug-Disease visual network analysis. And gene-ontology(GO) analysis and kyoto encyclopedia of genes and genomes(KEGG) pathway analysis of BLRGD targets were conducted using KOBAS online database. Protein-protein interaction(PPI) network was drawn by using STRING database and Cytoscape 3.7.1 software, and the results of GO and KEGG enrichment analysis were visualized by OmicShare platform and Cytoscape 3.7.1 software respectively. Results:A total of 36 active components of BLRGD, 116 target genes of BL-RGD and 3 063 target genes of HF-LC-PLC were obtained. 64 common genes were obtained by matching the two. The core components that are highly correlated with HF-LC-PLC by compound-target network and PPI network interaction are paeoniflorgenon, albiflorin, hederagenin,bisdemethoxycurcumin, etc. The core targets are IL6, MAPK8, CCND1, RELA, ICAM1 and so on, and the core pathways: Metabolic pathways, TNF, Pathways in cancer and so on.Conclusion:Treatment of BLRGD against HF-LC-PLC is a complex process of “multi-component multi-target multi-channel”, providing a theoretical basis for further study of the anti-HF-LC-PLC material basis and mechanism of BLRGD.