中国药物警戒 ›› 2024, Vol. 21 ›› Issue (4): 366-370.
DOI: 10.19803/j.1672-8629.20240051

• 养血安胎方对复发性自然流产的作用机制研究专栏 • 上一篇    下一篇

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

李心蕾1, 贡磊磊1△, 王晓霞2, 张雪艳1, 赵涵1, 姚伟洁1, 袁偲偲1#, 冯欣1,*   

  1. 1首都医科大学附属北京妇产医院,北京妇幼保健院药事部,北京 100026;
    2北京市肛肠医院药剂科,北京 100120
  • 收稿日期:2024-01-25 出版日期:2024-04-15 发布日期:2024-04-18
  • 通讯作者: *冯欣,女,硕士,主任药师,药理学与医院药学。E-mail: fengxin1115@ccmu.edu.cn,,#为共同通信作者。
  • 作者简介:李心蕾,女,本科,主管药师,妇产科临床药学。△为并列第一作者。
  • 基金资助:
    国家自然科学基金资助项目（82204783）; 北京市属医院科研培育计划项目（PZ2023029）; 首都医科大学附属北京妇产医院北京妇幼保健院2021年“中青年学科骨干培养专项”（FCYY202110）

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

LI Xinlei1, GONG Leilei1△, WANG Xiaoxia2, ZHANG Xueyan1, ZHAO Han1, YAO Weijie1, YUAN Sisi1#, FENG Xin1,*   

  1. 1Department of Pharmacy, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing Maternal and Child Health Care Hospital, Beijing 100026, China;
    2Beijing Anorectal Hospital, Beijing 100120, China
  • Received:2024-01-25 Online:2024-04-15 Published:2024-04-18

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摘要： 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。

关键词: 养血安胎颗粒, 复发性流产, 网络药理学, 分子对接, 作用机制, 多维网络分析

Abstract: 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 drug-disease 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 de-weighting. 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.

Key words: Yangxue Antai granules, recurrent spontaneous abortion, network pharmacology, molecular docking, mechanism, mutidimensional network

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