基于网络药理学探讨乌金胶囊抗肝细胞癌作用机制

Mechanism Exploration of Wujin Capsules against Hepatocellular Carcinoma based on Network Pharmacology

目的构建乌金胶囊活性成分-作用靶点网络和蛋白相互作用网络,对靶点涉及的功能以及通路进行分析,探讨乌金胶囊抗肝细胞癌作用机制。方法通过TCMSP数据库(http://lsp.nwu.edu.cn/tcmsp.php)获取乌金胶囊中延胡索、郁金、黄芪、山楂和通关藤的主要活性成分及其靶点,通过GenCards、OMIM、TTD、DRUGBANK数据库获取肝细胞癌疾病相关靶点。采用Cyto-scape构建活性成分-肝细胞癌靶点网络,并分析核心成分和靶点;利用String(http://string-bd.org)平台进行蛋白质相互作用分析;采用Metascape平台对靶点进行GO及KEGG通路分析。结果筛选得到乌金胶囊活性成分66个,作用于139个肝细胞癌靶点;核心活性成分有槲皮素、山柰酚、柚皮素和刺芒柄花素等,核心靶点包括TGS2、HSP90AA1和RXRA等;GO分析结果表明,乌金胶囊抗肝细胞癌的靶点主要涉及细胞对氮化合物的反应、蛋白质磷酸化的正向调节、细胞对有机环状化合物的反应、细胞对生长因子刺激的反应和细胞对化学应激的反应等生物过程。KEGG分析结果显示,乌金胶囊抗肝细胞癌作用的靶点主要涉及磷脂酰肌醇3激酶/蛋白激酶B信号通路、丝裂原活化蛋白激酶信号通路和肿瘤坏死因子等信号通路。结论乌金胶囊抗肝细胞癌作用具有多成分、多靶点与多通路的特点,其可能通过调节磷脂酰肌醇3激酶/蛋白激酶B、丝裂原活化蛋白激酶和肿瘤坏死因子等相关通路发挥作用。

Objective To explore the mechanism and effects of Wujin capsules against hepatocellular carcinoma by establishing an active components-targets network and protein interaction network in order to analyze the related functions and pathways of targets.Methods Data on the main active components and targets of Wujin capsules was retrieved from the TCMSP database.The disease targets of the main active components were predicted and screened via GeneCards,OMIM,TTD and DRUGBANK.The components-targets network was constructed by means of Cytoscape 6.1 before the core nodes were screened.The interactions between the protein targets were analyzed with the String database.GO and KEGG pathways related to the targets were analyzed using the Metascape database.Results The results showed that 66 active components of Wujin capsules were screened and 139 targets were obtained.The active components included quercetin,kaempferol,naringenin and formononetin while the core targets included TGS2,HSP90AA1,and RXRA.The results of gene ontology(GO)analysis suggested that these targets mainly involved cellular response to nitrogen compounds,positive regulation of protein phosphorylation,cellular response to organic cyclic compound,cellular response to growth factor stimulus,and cellular response to chemical stress.The results of Kyoto Encyclopedia of Genes and Genomes(KEGG)indicated that these targets chiefly involved PI3K/AKT,MAPK and TNF signaling pathways.Conclusion The protective effect of Wujin capsules against hepatocellular carcinoma is characterized by multiple components,multiple targets and multiple pathways.Such capsules may work by regulating PI3K/AKT,MAPK and TNF pathways.