神经药理学报 ›› 2025, Vol. 15 ›› Issue (6): 6-.DOI: 10.3969/j.issn.2095-1396.2025.06.002

• 研究论文 • 上一篇    下一篇

基于网络药理学研究赤芍防治肺癌的作用机制

魏子欣,夏蕾,刘家萌,邢浩宽,任金钊,温佳瑶,于聆汐,刘小雅,郭春燕   

  1. 河北北方学院药学院,河北省神经药理学重点实验室,张家口,075000,中国
  • 出版日期:2025-12-26 发布日期:2026-03-30
  • 通讯作者: 郭春燕,教授,硕士生导师;研究方向:体内药物分析和靶向药物分析
  • 作者简介:魏子欣,研究方向:网络药理学
  • 基金资助:
    河北省创新创业教育改革研究与实践项目(No.2023cxcy159)

Investigation of the Mechanism of Radix Paeoniae Rubra Preventing Lung Cancer Based on Network Pharmacology

WEI Zi-xin, XIA Lei, LIU Jia-meng, XING Hao-kuan, REN Jin-zhao, WEN Jia-yao, YU Ling-xi, LIU Xiao-ya, GUO Chun-yan   

  1. Department of Pharmacy, Hebei North University, Hebei Key Laboratory of Neuropharmacology, Zhangjiakou, 075000, China
  • Online:2025-12-26 Published:2026-03-30

摘要:

目的:通过网络药理学预测赤芍防治肺癌的作用机制。方法:通过TCMSP 数据库检索赤芍的化学成 分,通过SwissTarget Prediction 数据库预测赤芍的作用靶点。通过OMIM 数据库、GeneCards 数据库搜集肺癌 疾病相关靶点,筛选获得赤芍成分作用靶点与肺癌疾病相关靶点交集,利用String 平台搜集相关靶点蛋白,借 助DAVID 数据库进行GeneOntology 注释分析,并通过Cytoscape 3.9.1 软件进行可视化分析,通过Centiscape 2.2 插件软件构建蛋白- 蛋白相互作用网络(protein-protein interaction networks,PPI),得到核心靶点,通过蛋 白互作用网络、基因本体(gene ontology,GO) 和京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG) 分析得到了赤芍与肺癌关联度高的8 个靶点,在PubChem 数据库获取芍药苷、鞣花酸、黄芩素 的3D 结构,保存为Sdf 文件。选取部分靶点分别与芍药苷、鞣花酸、黄芩素进行分子对接,在Uniport 数据库和 PDB 数据库找到靶点信息,在AutodockVina 和Openbabel 进行分子对接得到对接能,通过PyMol 软件进行分子 对接可视化,最后再进一步分析赤芍防治肺癌作用机制。基于初始筛选的8 个关键基因,利用KEGG 筛选显著 关联的拓展通路,对这些通路上的所有靶点开展分子对接,以结合能≤ -5.0 kcal·mol-1 为标准评判对接效果。结 果:从中药赤芍中筛选得到13 个化合物成分以及563 个作用靶点,与2 376 个肺癌相关靶点取交集得到223 个 共同靶点,蛋白- 蛋白相互作用网络有222 个节点,4 678 条边,经筛选得到39 个节点,625 条边,核心靶点有39 个。GO 注释得到887 条生物过程,110 条细胞组分以及197 条分子功能的信息。赤芍与肺癌关联度高的8 个 靶点分别为ESR1、EGFR、KRAS2、KRAS、ERBB1、HRAS、MEK1、MAP2K1,其中与赤芍核心活性成分均显示良 好对接活性。基于初始筛选的8 个目标位点,经KEGG 筛选出显著关联的RAS-ERBB-MAPK 信号轴相关通路 为主要信号通路。筛选确定RAS-ERK、ERBB、MAPK、Ras 信号通路后,经过分子对接证实赤芍核心活性成分 均结合良好。结论:网络药理学直观地显示了赤芍可能通过RAS-ERBB-MAPK 信号轴上的RAS-ERK、ERBB、 MAPK 和Ras 信号通路的多靶点多通路协同抑制对肺癌的细胞增殖起到治疗作用, 为后续开发治疗肺癌的药物 提供了理论基础。

关键词: 肺癌, 网络药理学, 赤芍, 芍药苷

Abstract:

Objective: To predict the mechanism of radix paeoniae rubra in the prevention and treatment of lung cancer through network pharmacology. Methods: The chemical components of radix paeoniae rubra were retrieved from the TCMSP database, and its action targets were predicted using the SwissTarget Prediction database. The targets related to lung cancer were collected from the OMIM database and GeneCards database. The intersection of the targets of radix paeoniae rubra components and the targets related to lung cancer was screened.The related target proteins were collected using the String platform, and Gene Ontology annotation analysis was conducted with the DAVID database. Visualization analysis was performed using Cytoscape 3.9.1 software. The protein-protein interaction network was constructed using the Centiscape 2.2 plugin software to obtain the core targets. Through PPI, GO and KEGG analysis, 8 targets with high correlation between radix paeoniae rubra and lung cancer were obtained. The 3D structures of paeoniflorin, ellagic acid and baicalein were obtained from the PubChem database and saved as Sdf files. Molecular docking was performed between some of the targets and paeoniflorin, ellagic acid and baicalein. Target information was found in the Uniport database and PDB database. Molecular docking was conducted in AutodockVina and Openbabel to obtain the docking energy. Molecular docking visualization was performed using PyMol software. Finally, the mechanism of radix paeoniae rubra in the prevention and treatment of lung cancer was further analyzed. Based on the initial screening of 8 key genes, the significantly associated extended pathways were selected using KEGG, and molecular docking was conducted on all targets in these pathways. The docking effect was judged by the standard of binding energy ≤ -5.0 kcal·mol-1. Results: Thirteen compounds and 563 action targets were screened from the traditional Chinese medicine radix paeoniae rubra. The intersection with 2 376 lung cancer-related targets yielded 223 common targets. The protein-protein interaction network had 222 nodes and 4 678 edges. After screening, 39 nodes and 625 edges were obtained, and there were 39 core targets. GO annotation yielded 887 biological processes, 110 cellular components, and 197 molecular functions. The eight targets with high correlation between radix paeoniae rubra and lung cancer were ESR1, EGFR, KRAS2, KRAS, ERBB1, HRAS, MEK1, and MAP2K1, all of which showed good docking activity with the core active components of radix paeoniae rubra. Based on the initial screening of 8 target sites, the RAS-ERBB- MAPK signaling axis-related pathways were identified as the main signaling pathways through KEGG screening. After screening and determining the RAS-ERK, ERBB, MAPK, and Ras signaling pathways, molecular docking confirmed that the core active components of radix paeoniae rubra had good binding. Conclusion: Network pharmacology intuitively demonstrates that radix paeoniae rubra may exert therapeutic effects on the proliferation of lung cancer cells through the multi-target and multi-pathway synergistic inhibition of the RAS-ERBB-MAPK signaling axis, including the RAS-ERK, ERBB, MAPK, and Ras signaling pathways, providing a theoretical basis for the subsequent development of drugs for the treatment of lung cancer.

Key words: lung cancer, network pharmacology, radix paeoniae rubra, paeoniflorin

中图分类号: