吉林大学学报(医学版) ›› 2023, Vol. 49 ›› Issue (4): 913-922.doi: 10.13481/j.1671-587X.20230412

• 基础研究 • 上一篇    下一篇

西洋参茎叶三醇组皂苷抗缺血性脑卒中作用机制的网络药理学和分子对接分析

赖思含,刘俊彤,谭璐瑩,刘金平(),李平亚()   

  1. 吉林大学药学院天然药物研究中心,吉林 长春 130021
  • 收稿日期:2022-10-22 出版日期:2023-07-28 发布日期:2023-07-26
  • 通讯作者: 刘金平,李平亚 E-mail:liujp@jlu.edu.cn;lipy@jlu.edu.cn
  • 作者简介:赖思含(1997-),女,湖北省随州市人,在读硕士研究生,主要从事天然药物化学及其生物活性方面的研究。
  • 基金资助:
    吉林省科技厅重大科技专项项目(20200504006YY)

Network pharmacology and molecular docking analysis on anti-ischemic stroke mechanism of Panax quinquefolium triolsaponins

Sihan LAI,Juntong LIU,Luying TAN,Jinping LIU(),Pingya LI()   

  1. Research Center of Natural Drug,School of Pharmaceutical Sciences,Jilin University,Changchun 130021,China
  • Received:2022-10-22 Online:2023-07-28 Published:2023-07-26
  • Contact: Jinping LIU,Pingya LI E-mail:liujp@jlu.edu.cn;lipy@jlu.edu.cn

摘要:

目的 利用网络药理学和分子对接技术探讨西洋参茎叶三醇组皂苷(PQTS)在缺血性脑卒中(IS)发生发展过程中潜在的作用机制。 方法 整合Swiss Target Prediction、中医药百科全书(ETCM)、SEA Search Server和DisGeNET等数据库获取PQTS作用于IS的潜在靶点。利用STRING数据库和Cytoscape 3.9.1软件构建潜在作用靶点的蛋白-蛋白互作(PPI)网络,并通过拓扑网络分析得到PQTS作用于IS的核心靶点。通过DAVID在线分析网站进行潜在作用靶点的基因本体(GO)功能和京都基因与基因组百科全书(KEGG)信号通路富集分析,获取相关信号通路。应用Cytoscape 3.9.1软件构建PQTS-靶点-信号通路网络,进行拓扑网络分析,筛选PQTS潜在主要活性成分。通过AutoDock Vina软件对活性成分和核心靶点进行分子对接验证。 结果 得到PQTS作用IS的潜在作用靶点122个,GO功能富集分析主要涉及细胞凋亡调控、细胞内信号传导过程和细胞对外源性物质的调控等生物学过程,KEGG富集分析涉及白细胞介素信号通路、磷脂酰肌醇3-激酶/蛋白激酶B(PI3K/Akt)信号通路和PI3K/Akt/哺乳动物雷帕霉素靶蛋白(mTOR)信号通路。分子对接分析,拟人参皂苷F11、20(S)-原人参三醇、人参皂苷Rg1、人参皂苷Rh1、拟人参皂苷RT5和人参皂苷Re与信号转导和转录激活因子3(STAT3)、磷脂酰肌醇3-激酶催化亚基α(PIK3CA)、表皮生长因子受体(EGFR)和丝裂原活化蛋白激酶14(MAPK14)均能形成结合能较低的稳定构象。 结论 PQTS对IS的保护作用可能与STAT3、PIK3CA、EGFR和MAPK14及PI3K/Akt信号通路有关。

关键词: 西洋参茎叶三醇组皂苷, 缺血性脑卒中, 网络药理学, 分子对接, 磷脂酰肌醇3-激酶, 蛋白激酶B, 信号通路

Abstract:

Objective To discuss the potential mechanism of Panax quinquefolium triolsaponins (PQTS) in the occurrence and development of ischemic stroke by using network pharmacology and molecular docking technique. Methods The potential targets of PQTS acing on IS were obtained through Swiss Target Prediction Database, Encyclopedia of Traditional Chinese Medicine(ETCM) Database, SEA Search Server Database, DisGeNET Database, and so on; the protein-protein interaction (PPI) network diagram of the key potential targets was established by STRING Database and Cytoscape 3.9.1 software;the core tagets of PQTS acting on IS were got by topology network analysis; Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathway enrichment analysis were used to analyze the potential targets through DAVID online analysis website; the PQTS-target-signaling pathway network was constructed by Cytoscape 3.9.1 software and the topology network analysis was used to obtain the potential main active compositions; AutoDock Vina software was used to verify the molecular docking between the active ingredients and core targets. Results There were 122 potential targets of PQTS acting on IS; the GO function enrichment analysis was mainly included the regulation of apoptosis, intracellular signal transduction process, and regulations of extracellular substances by cells; the KEGG function analysis included the interleukins signaling pathways, phosphatidylinositol 3 kinase/protein kinase B (PI3K/Akt) signaling pathway and phosphatidylinositol 3 kinase-protein kinase B-mammalian target of rapamycin (PI3K-Akt-mTOR) signaling pathway. The molecular docking analysis results showed that pseudo-ginsenoside F11, 20(S)-protopanaxatriol, ginsenoside Rg1, ginsenoside Rh1, pseudo-ginsenoside RT5, and ginsenoside Re could form the stable conformations with signal transducer and activator of transcription 3(STAT3),phosphatidylinositol 3-kinases catalytic suburit α(PIK3CA),epidermal growth factor receptor (EGFR), and mitogen-activated protein kinase 14(MAPK14) with lower binding energy. Conclusion The protective effect of PQTS on IS may be related to the STAT3, PIK3CA, EGFR, MAPK14, and PI3K/Akt signaling pathways.

Key words: Panax quinquefolium triolsaponins, Ischemic stroke, Network pharmacology, Molecular docking, Phosphatidylinositol 3-kinase, Protein kinase B, Signaling pathway

中图分类号: 

  • R285.5