基于网络药理学和分子对接技术探讨蒙药梅花草治疗肝损伤的潜在作用机制

Reseach on The Mechanism of Mongolian Medicine Parnassia Palustris in Treating Liver Injury Based on Network Pharmacology and Molecular Docking Technology

目的:应用网络药理学和分子对接技术探究蒙药梅花草治疗肝损伤的作用机制,为梅花草的进一步研究与应用提供参考依据。方法:基于TCMSP和Swiss Target Prediction数据库筛选蒙药梅花草的活性成分及靶点,通过GeneCards和OMIM数据库查找肝损伤的相关靶点,再将梅花草活性成分靶点与疾病靶点映射,采用Cytoscape 3.8.0绘制PPI网络构建图,并进行GO功能富集和KEGG通路富集分析,进一步构建活性成分-靶点-信号通路网路图,最后运用AutoDock软件将蒙药梅花草主要活性成分与肝损伤核心靶点进行分子对接。结果:通过筛选得到梅花草活性成分28个;药物与疾病共同作用靶点751个;蛋白互作用网络中核心靶点为TP53(肿瘤蛋白P53)、SRC(酪氨酸蛋白激酶)、HSP90AA1(蛋白质编码基因)、AKT1(丝氨酸/苏氨酸蛋白激酶)、MAPK3(丝裂原活化蛋白激酶3)、STAT3(信号转导子和转录激活子3)、CTNNB1(β-连环蛋白)、MAPK1(丝裂原激活的蛋白激酶1)、EGFR(人表皮生长因子受体)、EP300(E1A结合蛋白P300)等。分子对接结合能均<-7kcal/mol,表明药物活性成分与靶点蛋白对接效果良好,与网络药理预测结果相符。结论:蒙药梅花草以多成分、多靶点、多通路的复杂形式发挥治疗肝损伤的作用,TP53、AKT1、MAPK1、MAPK3等可能参与其中。

Objective:To study the mechanism of Mongolian medicine Parnassia palustris in relieving liver injury.Methods:The active compounds and corresponding targets were collected by consulting the relevant literature and TCMSP,and Swiss Target Prediction database.GeneCards and OMIM databases were used to collect disease targets for liver injury.Venny 2.1.0 was used to obtain the common targets,and the intersection was taken to obtain the intersecting targets,and the medicinal material-chemical composition-target-disease network was established.The protein-protein interaction(PPI)network diagram of the above potential targets was established through the STRING platform,and the gene ontology(GO)and kyoto encyclopedia of genes and genomes(KEGG)annotation analysis of the targets were performed through the David database.Cytoscape 3.8.2 software was used to construct the active ingredient-target-signaling pathway network diagram of Mongolian medicine Parnassia palustris,and the main active ingredients,core targets and signaling pathways were screened.The results of network pharmacology analysis were verified by Autodock.Results:28 active ingredients of Parnassia palustris were screened,and 751 targets of drug disease interaction were identified.The core targets are TP53,SRC,HSP90AA1,AKT1,MAPK3,STAT3,CTNNB1,MAPK1,EGFR,EP300,etc.The binding energies of molecular docking are all less than-7kcal/mol,indicating a good docking effect between the active ingredients of the drug and the target protein,which is consistent with the network pharmacological prediction results.Conclusion:Mongolian medicine Parnassia palustris plays a therapeutic role in liver injury through multiple components,targets,and pathways.