基于网络药理学和分子对接探讨培元补肾安胎方治疗复发性流产的作用机制

Mechanism of treating recurrent abortion with“Peiyuan BushenAntaiformula”based on network pharmacology and molecular docking

目的:培元补肾安胎方临床治疗复发性流产取得了良好的疗效,但由于其成分复杂,其治疗复发性流产的机制尚未阐明。本项研究应用网络药理学研究培元补肾安胎方治疗复发性流产的有效化合物、作用靶点、信号通路等,从而揭示其治疗复发性流产的作用机制。方法:应用TCMSP、TCM获取培元补肾安胎方的主要化合物和药物作用靶点,并检索Genecards、OMIM数据库收集已知的关于复发性流产的基因,从而构建药物-化合物-靶点网络图,筛选出共同靶点蛋白和主要化合物。使用String构建可视化蛋白-蛋白互作网络图(PPI)。应用clusterProfiler和R语言软件对药物与疾病的共同靶点进行GO功能分析和KEGG通路富集分析。最后,根据化合物和蛋白的相关节点参数进行排序,对核心蛋白和核心化合物进行分子对接。结果:筛选出培元补肾安胎方186个潜在活性成分和136个作用预测靶点。RSA相关基因1658个,其中有65个与培元补肾安胎方的靶点相重叠,被认为与治疗有关。PPI网络显示VEGFA、IL-6、EGFR、MAPK8、ESR1等是培元补肾安胎方治疗复发性流产的核心靶点。GO和KEGG富集分析得到50个细胞生物学过程(P<0.05)和62条信号通路(P<0.05),培元补肾安胎方通过抗炎、抗凋亡、促增殖、血管生成等途径来发挥治疗复发性流产的药理作用。分子对接表明,培元补肾安胎方的大多数活性成分和关键靶点具有较强的结合效率。结论:通过网络药理学研究揭示了培元补肾安胎方可通过多个靶点、多个信号通路来治疗复发性流产,为进一步研究其作用机制提供了理论基础。

Objective:To study the effective compound action target signalpathway of Peiyuan Bushen Antaiformula(PYBSATF)in the treatment of recurrent abortionby applyingnetwork pharmacology and molecular docking,so as to reveal its action mechanism in the treatment of recurrent abortion.Methods:TCMSP and TCM were usedto obtain the main compounds and drug targets of PYBSATF,and to retrieve the known genes about recurrent abortion collected from Genecards OMIM database,so as to construct the drug-compound-target network map and screen outthe common target proteins and main compounds.A visual protein-protein interaction(PPI)network graph was constructed with Stringdatabase.ClusterProfiler and R language software were used to analyze the GO function and the KEGG pathway enrichment of the common targets of drugs and diseases.Finally,the molecular docking of the core protein and the core compound was carried out by sorting the relevant node parameters of the compound and the protein.Results:A total of 186 potential active ingredients and 136 potential action prediction targets of PYBSATF were screened.There were 1658 RSA related genes,among which 65 overlapped with the target of PYBSATF,which was considered to be related to treatment.PPI network showed that VEGFA,IL6,EGFR,MAPK8,ESR1 and so on were the core targets of PYBSATF in the treatment of recurrent abortion.And50 cell biological processes and 62 signaling pathways were obtained by GO and KEGG enrichment analysis(P<0.05).PYBSATF played a pharmacological role in the treatment of recurrent abortionthrough anti-inflammatory,anti-apoptotic,proliferative and angiogenic approaches.Molecular docking showed that most of the active components and key targets of PYBSATF had strong binding efficiency.Conclusion:Through the research of network pharmacology,it is revealed that PYBSATF can treat recurrent abortion through multiple targets and multiple signaling pathways,which provides a theoretical basis for further research on its mechanism of action.