基于网络药理学和分子对接探讨养血安胎颗粒治疗复发性流产分子作用机制

Molecular mechanism of Yangxue Antai granules for the treatment of recurrent spontaneous abortion based on network pharmacology and molecular docking

目的基于网络药理学和分子对接技术研究养血安胎颗粒治疗复发性流产(RSA)作用机制。方法通过中药系统药理学数据库与分析平台(TCMSP)和中医药整合药理学研究平台(TCMIP)数据库收集养血安胎颗粒主要化学成分及其映射靶标,通过OMIM、GeneCards、Drugbank、PharmGkb、TTD数据库收集RSA疾病靶标,并通过在线工具draw venn diagram分析药物与疾病靶标交集,导入STRING数据库,分析共有靶标相互作用关系(PPI),并对其进行生物信息学分析。此外,根据Degree值分析养血安胎颗粒治疗RSA的核心靶标,采用分子对接技术,研究靶标与化学成分之间结合度,验证网络药理学分析结果。结果共收集养血安胎颗粒化学成分70个和靶标236个,疾病靶标去重后获得453个。通过交集分析共获得66分共有靶标。PPI互作分析发现IL6、MMP9、TNF、IL1B、IL10等靶标是养血安胎颗粒治疗RSA核心靶标。生物信息学富集分析发现,这些共有靶标主要作用于TNF信号通路、HIF-1信号通路、FoxO信号通路、雌激素信号通路等信号通路。进一步的分子对接结果表明,度值(degree)靠前的靶标MMP9与芍药苷、芝麻素、槲皮素和山柰酚对接良好。尤其是芍药苷对接结果优于阳性对照。结论通过网络药理学和分子对接分析,发现养血安胎颗粒中主要活性成分通过作用于MMP9影响多条信号通路发挥治疗RSA作用。

Objective To reveal the mechanism of Yangxue Antai granules(YXATG)in the treatment of Recurrent spontaneous abortion(RSA)based on network pharmacology and molecular docking.Method The main chemical components and their targets of YXATG were collected from TCM Systematic Pharmacology Database and Analysis Platform(TCMSP)and TCM Integrated Pharmacology Research Platform(TCMIP)databases.The targets for RSA were identified from OMIM,GeneCards,Drugbank,PharmGkb and TTD databases.The intersection of drugs and disease targets was analyzed by drawing venn diagram,an online tool,and imported into the database,and analyzed the drugdisease target intersection through the online tool draw venn diagram,imported into STRING database,analysed the shared target interaction relationship(PPI),and performed bioinformatics analysis on it.In addition,the core targets of YXATG for RSA were analyzed according to Degree value,and molecular docking technology was used to study the binding degree between the targets and chemical components to validate the results of network pharmacological analysis.Results A total of 70 chemical components and 236 targets of YXATG were collected,and 453 disease targets were obtained after deweighting.A total of 66 common targets were obtained by intersection analysis,and PPI interaction analysis revealed that IL6,MMP9,TNF,IL1B and IL10 were the core targets of YXATG for the treatment of RSA.Bioinformatics enrichment analysis revealed that these common targets mainly acted in TNF signaling pathway,HIF-1 signaling pathway,FoxO signaling pathway,estrogen signaling pathway and other signaling pathways.Further molecular docking results showed that the target MMP9 with the highest degree value docked well with paeoniflorin,sesamin,quercetin and kaempferol.Especially,paeoniflorin docked better than the positive control.Conclusion Through network pharmacology and molecular docking analysis,it was found that the main active ingredients in YXATG exerted their therapeutic effects on RSA by affecting multiple signaling pathways through their action on MMP9.