基于网络药理学和分子对接的马齿苋治疗肝癌作用机制研究

Study on Mechanism of Portulacae Herba in the Treatment of Hepatocellular Carcinoma based on Network Pharmacology and Molecular Docking

目的:基于网络药理学和分子对接技术探讨马齿苋治疗肝癌的物质基础及其潜在作用机制。方法:经TCMSP平台筛选和文献挖掘来收集马齿苋的主要活性成分,通过PharmMapper和GeneCards数据库筛选出马齿苋活性成分的肝癌靶点。运用String数据库结合Cytoscape软件进行肝癌靶点蛋白相互作用网络构建和分析。运用Cytoscape的ClueGO和CluePedia插件对马齿苋潜在作用的肝癌靶点进行基因功能(GO)分析。运用DS软件对马齿苋的活性成分与肝癌靶点进行分子对接验证。结果:筛选得到马齿苋15个主要活性成分,涉及42个靶点及相关信号通路10个。网络分析结果表明马齿苋通过作用于MAPK1、IGF1、AKT1、HRAS、ALB和GRB2等关键靶点发挥抗肝癌作用。分子对接结果表明至少有9个活性成分能与MAPK1发生相互作用,其中杨梅黄酮(Myricetin)和MAPK1能稳定地结合并通过氨基酸残基ILE29、LYS52和GLN103等发生作用。结论:马齿苋治疗肝癌具有多靶点和多通路的潜在作用机制;黄酮类成分可能是其抗肝癌的主要物质基础,与调控MAPK信号通路有关。

Objective:To explore the material basis and the potential mechanism of Portulacae Herba in the treatment of hepatocel⁃lular carcinoma based on network pharmacology and molecular docking.Methods:TCMSP platform screening and literature mining were used to screen the main active ingredients of Portulacae Herba.The PharmMapper and GeneCards databases were used to screen the hepatocellular carcinoma targets of active constituents in Portulacae Herba.String database combined with Cytoscape software was used to construct and analyze the hepatocellular carcinoma targets protein interaction network.ClueGO and CluePedia plug⁃ins in Cytoscape software were used to analyze gene function(GO)of potential hepatocellular carcinoma targets of Portulacae Herba.DS software was used to verify the molecular docking between the active components of Portulacae Herba and hepatocellular carcinoma targets.Results:15 main active components of Portulacae Herba were screened,involving 42 targets and 10 related signaling pathways.The results of network analysis showed that Portulacae Herba acted on key targets such as MAPK1,IGF1,AKT1,HRAS,ALB and GRB2 to play an anti⁃hepatoma role.Molecular rendezvous results showed that there were at least nine active components that could interact with mAPK1,among which Myricetin and MAPK1 could bind stably and act through amino acid residues ILE29,LYS52 and GLN103.Conclusion:Portulacae Herba has multi⁃targets and multi⁃pathways potential mechanism in the treatment of liver canc⁃er.Flavonoid may be the main substance basis of its anti⁃hepatoma,which is related to the regulation of MAPK signaling pathway.