基于加权网络药理学的小柴胡汤抗肝癌作用机制研究

Study on anti-hepatoma mechanism of Xiaochaihu decoction based on weighted network pharmacology

目的通过加权网络药理学方法探索小柴胡汤抗肝癌的作用机制。方法利用TCMSP数据库和文献挖掘相结合的方法收集小柴胡汤的有效活性成分;利用PubChem数据库进行靶点预测并利用"肘点法"筛选优化得到药物靶点集,利用OMIM、Gene Cards、DisGeNET、TTD数据库获取肝癌的疾病靶点集,利用GEO数据库获取肝癌的差异表达基因集;利用STRING数据库构建靶点蛋白互作(PPI)网络并进行GO富集分析和KEGG通路分析;提出了构建化合物-靶点-通路加权网络的方法并进行加权分析,获取加权后的关键靶点和通路;利用Cytoscape构建活性成分-靶点-通路网络图。结果筛选得到182个有效成分,1241个药物靶点,896个疾病靶点,1569个差异表达基因,最终筛选出907个肝癌靶点。GO功能分析主要与蛋白质激酶活性、催化活性、药物结合等调控有关;KEGG通路主要涉及癌症信号通路、MAPK信号通路、PI3K-Akt信号通路等。结论小柴胡汤抗肝癌的关键靶点为GAPDH、TP53、ESR1、AKT1、MAPK1等,通过干预癌症信号通路、MAPK信号通路、PI3K-Akt信号通路等发挥抗肝癌作用,体现了中药多成分、多靶点、多通路协同作用机制的特点。

The mechanism of Xiaochaihu decoction in the treatment of liver cancer was explored by weighted network pharmacology in this study.First,182 active components of Xiaochaihu decoction were screened with TCMSP database and literature mining.Then PubChem database was used to predict the target and TCMKD software was used for optimization with inflection-point-method and 1241 drug targets were screened.OMIM,GeneCards,DisGeNET and TTD databases were used to obtain 896 disease targets of liver cancer.1569 Differentially expressed genes of liver cancer were obtained by GEO database,and 907 liver cancer targets were screened at last.Next,STRING database was used to construct the protein-protein interaction(PPI)network,and GO function enrichment analysis and KEGG pathway enrichment analysis were carried out.Finally,weighted analysis was carried out based on the weighted network of TCM ingredient-target-pathway to get the core targets and pathways.The results of weighted analysis showed that the key anti-liver cancer targets of Xiaochaihu decoction were GAPDH,TP53,ESR1 AKT1,MAPK1,etc.GO functions of TCM-disease targets included protein kinase activity,catalytic activity,drug binding etc.It showed that Xiaochaihu decoction could play an anti-hepatoma effect by interfering with cancer signaling pathway,MAPK signaling pathway and PI3 K-Akt signaling pathway,etc.,which embodies the characteristics of multi-component,multi-target and multi-pathway synergistic mechanism of traditional Chinese medicine.