基于网络药理学结合分子动力学模拟探究七气消聚散治疗肝硬化的作用机制

Exploring the mechanism of action of Qiqixiaoju powder in the treatment of liver cirrhosis based on network pharmacology combined with molecular dynamics simulation

目的采用网络药理学方法结合分子对接探究七气消聚散(QQXJ)治疗肝硬化的潜在机制,为其治疗肝硬化提供理论依据。方法使用TCMSP数据库获取QQXJ的药物作用基因,并从DisGeNET、DrugBank、GeneCards、OMIM、TTD数据库获得肝硬化疾病基因。将药物与疾病的交集基因导入至String平台构建蛋白互作(PPI)网络,并进行GO和KEGG通路富集分析、生物信息学分析、分子对接和分子动力学模拟。结果获得QQXJ与肝硬化共55个交集基因,其中MYC、RELA、CCND1、TP53为肝硬化治疗的关键靶点。分子对接实验及分子动力学模拟分析提示,木犀草素-CCND1复合物有较好的稳定性。富集分析结果显示QQXJ可调节P53、PI3K/AKT、丙型肝炎等多种通路。结论QQXJ可通过多成分、多靶点、多通路影响肝硬化进展,其可能通过抗炎和影响细胞凋亡来治疗肝硬化。

Objective To investigate the potential mechanism of Qiqixiaoju powder(QQXJ) in the treatment of liver cirrhosis based on a network pharmacological approach combined with molecular docking to provide a theoretical basis for the treatment of liver cirrhosis with QQXJ.Methods Drug acting genes of QQXJ were obtained from TCMSP database,and liver cirrhosis genes were obtained from DisGeNET,DrugBank,GeneCards,OMIM and TTD databases.The intersection genes of drugs and diseases were imported into String platform to construct the protein-protein interaction network(PPI),and GO and KEGG pathway enrichment analysis,bioinformatics analysis,molecular docking,and molecular dynamics simulation were performed.Results A total of 55 intersection genes of QQXJ and liver cirrhosis were obtained,among which MYC,RELA,CCND1 and TP53 were the key targets for the treatment of liver cirrhosis.Molecular docking and molecular dynamics simulation showed that the luteolin-CCND1 complex had good stability.Enrichment analysis showed that QQXJ could regulate P53,PI3K/AKT,hepatitis C and other pathways.Conclusion QQXJ can affect the progression of liver cirrhosis through multiple components,multiple targets and multiple pathways,and treats liver cirrhosis possibly through anti-inflammatory and affecting cell apoptosis.