基于网络药理学和分子对接探讨护肝宁片治疗乙型肝炎的作用机制

Exploration on the Mechanism of Huganning Tablets in the Treatment of Hepatitis B Based on Network Pharmacology and Molecular Docking

目的:通过网络药理学研究护肝宁片治疗乙型肝炎的作用机制。方法:利用TCMSP数据库收集护肝宁片活性成分,构建化合物—靶点图。通过GeneCards和OMIM数据库获取乙型肝炎相关靶点,将护肝宁片活性成分靶点与乙型肝炎疾病靶点取交集,得到关键靶点。通过对共有核心靶点进行蛋白质相互作用分析,分析蛋白相互作用(PPI)中度中心度(DC)、中间性中心性(BC)、紧密性中心性(CC)筛选核心靶基因。选取的护肝宁片主要活性成分与关键靶点进行分子对接。结果:筛选到护肝宁片中木樨草素、槲皮苷、隐丹参酮、丹参酮等81种主要化学成分和198个相关靶点,其中关键靶点有TP53、AKT1、VEGFA、STAT3等。护肝宁片中的活性成分可能通过线粒体、膜筏等细胞组分参与DNA生物合成、细胞凋亡、星形胶质细胞的激活等多种生物学过程,作用通路为乙型肝炎、PI3K-AKT等。分子对接结果显示主要化学成分与核心靶点的结合力均较强,蛋白结晶复合物构象稳定。结论:研究初步表明了护肝宁片通过多成分、多靶点、多通路发挥治疗乙型肝炎的作用机制。

Objective:To study the mechanism of Huganning tablets in the treatment of hepatitis B through network pharmacology.Methods:The active components of Huganing tablets were collected by TCMSP database,and the compound target map was constructed.Hepatitis B related targets were obtained from GeneCards and OMIM databases,and the key targets were obtained by intersection of the active component targets of Huganning tablets and the disease targets of hepatitis B.Protein interaction analysis was performed on shared core targets,and protein interaction(PPI)moderate centrality(DC),intercentrality(BC)and closeness centrality(CC)were analyzed to screen core target genes.The main active ingredients of Huganning tablets were selected for molecular docking with key targets.Results:81 main chemical components including luteolin,quercetin,cryptotanshinone and tanshinone in Huganning tablets and 198 related targets were screened,among which the key targets were TP53,AKT1,VEGFA,STAT3,etc.The active components in Huganning tablets may participate in DNA biosynthesis,cell apoptosis,astrocyte activation and other biological processes through mitochondria,membrane rafts and other cellular components,and the action pathways are hepatitis B and PI3K-AKT.The results of molecular docking showed that the binding force between the main active components and the core target was strong,and the conformation of the protein crystalline complex was stable.Conclusion:The study preliminarily showed that Huganning tablets play a role in the treatment of hepatitis B through multiple components,multiple targets and multiple pathways.