神经药理学报

神经药理学报 ›› 2023, Vol. 13 ›› Issue (2): 15-.DOI: 10.3969/j.issn.2095-1396.2023.02.003

• 研究论文 • 上一篇    下一篇

基于网络药理学与分子对接探讨三七治疗胃癌的作用机制及药效活性物质

辜雅萍，何燕彬，倪卓娜，黄彬，林久茂   

  1. 1. 福建中医药大学中西医结合研究院，福州，350122,中国  2. 福建省中西医结合老年性病重点疾病实验室，福州，350122，中国  3. 福建省高校中西医结合基础重点实验室，福州，350122，中国  4.福州经济技术开发区医院，福州，350015，中国
  • 出版日期:2023-04-26 发布日期:2023-11-30
  • 通讯作者: 林久茂，医学博士，研究员，博士生导师；E-mail：linjiumao@fjtcm.edu.cn
  • 作者简介:辜雅萍，硕士研究生，医师；研究方向：中西医结合肿瘤研究；E-mail：gugu99_66@163.com
  • 基金资助:
    福建省自然科学基金项目(No.2019J01355)

To Explore the Mechanism of Action and Active Substances of Panax Notoginseng in the Treatment of Gastric Cancer Based on Network Pharmacology and Molecular Docking

GU Ya-ping，HE Yan-bin，NI Zhuo-na，HUANG Bin，LIN Jiu-mo   

  1. 1. Institute of Integrated Traditional Chinese and Western Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, 350122, China

    2. Fujian Provincial Key Laboratory of Integrated Traditional Chinese and Western Medicine for Senile Sexually Transmitted Diseases, Fuzhou, 350122, China

    3. Fujian Provincial Key Laboratory of Integrated Traditional Chinese and Western Medicine, Fuzhou, 350122, China

    4. Fuzhou Economic and Technological Development Zone Hospital, Fuzhou, 350015, China

  • Online:2023-04-26 Published:2023-11-30

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摘要：

目的：通过网络药理学和分子对接技术探讨中药八宝丹中唯一已知植物成分三七治疗胃癌的潜在药效活性成分及其作用机制。方法：通过TCMSP 等数据库筛选三七的有效活性成分及相关靶点蛋白，将GeneCards和DisGeNET等数据库挖掘的胃癌相关靶点和药物靶点蛋白交集；采用 Cytoscape3.7.0对药效成分进行分析，建立有效的成分-靶点-疾病的关系模型。运用STRING数据库构建交集靶点的PPI蛋白互作图。运用 David 数据库进行KEGG通路和GO分类的富集分析；利用AutoDock Tools 1.5.6软件对三七关键活性成分和核心靶点进行分子对接验证，运用PyMol 2.5软件绘制对接模式图。结果：筛选出三七的有效活性成分99个，映射273个药靶基因。经GeneCards数据库搜集得到胃癌疾病基因15118个，三七与胃癌的交集靶点234个，分析得到165条KEGG富集通路，195条GO功能富集条目，主要包括癌症的途径、PI3K-Akt通路、MAPK通路、Ras通路，以及RNA聚合酶启动子转录的正向调节、信号转导、基因表达的正调控、正调节细胞增殖、负调节细胞凋亡等生物过程；其中高Hub值的化合物成分豆甾醇、人参皂苷rh2与胃癌基因白细胞介素6（interleukin-6，IL-6）、TP53、肿瘤坏死因子（tumor necrosis factor, TNF）存在较强的分子对接关系。结论：三七治疗胃癌的机制涉及多成分、多靶点和多途径，三七可能是通过调节癌症的途径、PI3K/Akt通路、MAPK通路、Ras信号通路等在胃癌治疗中发挥作用，其中豆甾醇、人参皂苷rh2可能是三七药效的关键活性成分之一。

关键词: 三七, 胃癌, 网络药理学, 分子对接

Abstract:

Objective: Through network pharmacology and molecular docking technology, the only known plant component of Babaodan in the treatment of gastric cancer potential active ingredients and its mechanism of action. Methods: The active ingredients and related target proteins of Panax Notoginseng were screened by TCMSP and other databases, and the gastric cancer related targets and drug target proteins mined by GeneCards and DisGeNET databases were intersected. Cytoscape3.7.0 was used to analyze pharmacodynamic components to establish an effective component-target-disease relationship model. The PPI protein interaction map of intersecting targets was constructed by using String database. The enrichment analysis of KEGG pathway and GO classification was carried out using David database. AutoDock Tools 1.5.6 software was used to verify the molecular docking of key active ingredients and core targets of Panax Notoginseng, and PyMol 2.5 software was used to draw the docking model diagram. Results: 99 active ingredients of Panax Notoginseng were selected and 273 target genes were mapped. Through GeneCards database, 15118 gastric cancer disease genes and 234 intersection targets of Notochi and gastric cancer were collected, and 165 KEGG enrichment pathways and 195 GO functional enrichment items were obtained, mainly including cancer pathway, PI3K-Akt pathway, MAPK pathway and Ras pathway. And RNA polymerase promoter transcription positive regulation, signal transduction, gene expression positive regulation, positive regulation of cell proliferation, negative regulation of cell apoptosis and other biological processes; Among them, stigasterol and ginsenoside rh2 with high Hub value had strong molecular docking relationship with gastric cancer genes IL6, TP53 and TNF. Conclusion: Panax Notoginseng may play a role in the treatment of gastric cancer through regulating cancer pathways, PI3K/Akt pathway, MAPK pathway and Ras signaling pathway, among which stigmosterol and ginsenoside rh2 may be one of the key active ingredients of Panax notoginseng.

Key words:

notoginseng, gastric cancer, network pharmacology, molecular docking