天然产物研究与开发 ›› 2023, Vol. 35 ›› Issue (增刊2): 116-124.

• 数据研究 • 上一篇    下一篇

基于网络药理和分子对接探究和枢消积丸干预肝癌的机制

陈相霖1,彭昭宣2,张玉蓉2,彭一宸1,汪   静2*   

  1. 1西南医科大学;2西南医科大学附属中医医院,泸州 646000
  • 出版日期:2023-12-28 发布日期:2023-12-11
  • 基金资助:
    四川省中医药管理局中医药科研专项(川科计〔2018〕4号,2020IC0142);泸州市"酒城英才·科技创新团队"(泸组通\[2021\]162号);泸州市政府-西南医科大学科技战略合作项目(2021LZXNYD-Z08);四川省中医药管理局中医药科研专项(川中医药办发\[2021\]13号)

Intervention mechanism of Heshu Xiaoji pills on liver cancer based on network pharmacology and molecular docking

CHEN Xiang-lin1,PENG Zhao-xuan2,ZHANG Yu-rong2,PENG Yi-chen1,WANG Jing2*   

  1. 1Southwest Medical University; 2Affiliated Traditional Chinese Medicine Hospital,Southwest Medical University,Luzhou 646000, China
  • Online:2023-12-28 Published:2023-12-11

摘要:

基于网络药理-分子对接探析和枢消积丸干预肝癌的机制。从TCMSP、SymMap、GeneCards、OMIM、DurgBank、TTD和PharmGKB数据库内筛选出15味中药主要活性成分及治疗肝癌的作用靶点,应用STRING平台构建蛋白-蛋白相互作用(PPI)网络模型。采用Cytoscape软件绘制药物-成分-共有靶点网络和Metascape工具对共有靶点进行GO功能富集分析和KEGG通路富集分析,最后采用AutoTools软件进行分子对接验证。最终获取数据库中活性成分-疾病共同靶点251个;共同靶点的拓扑分析筛选出21个核心关键基因,度值靠前的4位关键基因是JUN、MAPK3、MAPK1和TP53;并通过分子对接证明,药物有效成分与4个核心基因对接良好,其中柚皮素和MAPK3结合能最高;GO富集分析显示,和枢消积丸调节药物的反应、氧化应激反应、核受体活性和转录因子活性等生物过程参与肝癌发生发展;KGEE富集通路分析,主要核心靶点与肝癌相关的信号通路主要涉及钙离子信号通路、PI3K-Akt信号通路、P53信号通路、TGF-β信号通路、Wnt信号通路和MAPK信号通路。通过分子对接与网络药理的探析,发现和枢消积丸治疗肝癌疾病的作用机制涉及多成分、多靶点和多通路,为临床应用和基础研究提供了科学依据。

Abstract:

To explore the mechanism of Heshu Xiaoji pills (HXP) intervention in liver cancer based on network pharmacology-molecular docking.fifteen major active ingredients of TCM and their targets for the treatment of liver cancer were first screened from TCMSP,SymMap,GeneCards,OMIM,DurgBank,TTD and PharmGKB databases,and then protein-protein interaction (PPI) network models were constructed by applying the STRING platform.Cytoscape software was used to map the drug-component-shared target network and Metascape tool to perform GO functional enrichment analysis and KEGG pathway enrichment analysis on the shared targets,and then AutoTools software was used for molecular docking validation.Finally,251 active ingredient-disease common targets were obtained from the database.Target intersection analysis screened 21 core key genes,and the top 4 key genes were JUN,MAPK3,MAPK1 and TP53.Molecular docking demonstrated that the active ingredients of the drug dovetailed well with four core genes,among which naringenin and MAPK3 had the highest binding energy.GO enrichment analysis showed that the biological processes such as the response to drug,oxidative stress,nuclear receptor activity and transcription factor activity were involved in the development of hepatocellular carcinoma.KGEE enrichment pathway analysis showed that the main core targets and hepatocellular carcinoma-related signaling pathways mainly involved the calcium signaling pathway,PI3K-Akt signaling pathway,P53 signaling pathway,TGF-β signaling pathway,Wnt signaling pathway and MAPK signaling pathway.Through the analysis of molecular docking and network pharmacology,it was found that the mechanism of action of HXP in treating liver cancer disease involves multiple components,multiple targets and multiple pathways,which provides a scientific basis for clinical application and basic research.

Key words: Heshu Xiaoji pills, network pharmacology, molecular docking, liver cancer, mechanism of action

中图分类号:  R285