基于网络药理学和分子对接探讨慈丹胶囊治疗肝癌的作用机制  

Mechanisms of Cidan capsules in the treatment of liver cancer based on network pharmacology and molecular docking

作　　者：李坤 马壮士 董玲芳 高山 马培志 张伟 LI Kun;MA Zhuang-shi;DONG Ling-fang;GAO Shan;MA Pei-zhi;ZHANG Wei(Department of Pharmacy,Henan Provincial People’s Hospital,People’s Hospital of Zhengzhou University,People’s Hospital of Henan University,Zhengzhou 450003,Henan Province,China;Key Laboratory of Structure-Based Drugs Design&Discovery,Ministry of Education,Shenyang Pharmaceutical University,Shenyang 110016,Liaoning Province,China)

机构地区：[1]河南省人民医院、郑州大学人民医院、河南大学人民医院药学部,河南郑州450003 [2]沈阳药科大学基于靶点的药物设计与研究教育部重点实验室,辽宁沈阳110016

出　　处：《中国临床药理学杂志》2022年第22期2766-2770,共5页The Chinese Journal of Clinical Pharmacology

基　　金：国家自然科学基金资助项目(81803357);河南省重点研发与推广专项基金资助项目(科技攻关182102310273)。

摘　　要：目的用网络药理学和分子对接方法探索慈丹胶囊治疗肝癌的潜在作用机制。方法通过检索中药系统药理学数据库与分析平台及相关文献收集慈丹胶囊的活性成分和作用靶标,并用Cytoscape-3.8.0软件构建中药组分-活性成分-关键靶点网络图。用基因名片数据库筛选肝癌的潜在靶点信息。基于蛋白质相互作用数据库构建慈丹胶囊和肝癌交集靶点蛋白的互作网络图。用注释、可视化和集成发现数据库将交集靶点进行基因本体生物过程富集分析和京都基因与基因百科全书信号通路富集分析。通过分子对接考察关键活性成分与潜在靶点蛋白的作用方式。结果慈丹胶囊可能通过槲皮素、山柰酚、木犀草素等59个主要活性成分作用于肿瘤抑制蛋白p53、肌动蛋白、丝/苏氨酸蛋白激酶1等127个关键靶点,进而调控癌症相关通路、磷脂酰肌醇3激酶-丝/苏氨酸激酶通路等肿瘤相关信号通路,诱导细胞周期阻滞和凋亡,从而达到治疗肝癌的目的。分子对接结果显示,慈丹胶囊中主要活性成分能够与多个度值较高的关键核心靶点很好地结合,进而可能对靶点蛋白产生激活或抑制作用。结论慈丹胶囊治疗肝癌的潜在作用机制具有多成分、多靶点、多通路的作用特点。Objective To explore the potential mechanism of Cidan capsules in the treatment of liver cancer based on network pharmacology and molecular docking.Methods The active ingredients and targets of Cidan capsules were collected by searching traditional Chinese medicine systems pharmacology database and analysis platform as well as related literatures.Cytoscape-3.8.0 software was used to construct the network diagram of Chinese herb-active ingredient-key target.The GeneCards database was applied to obtain potential targets for liver cancer.Based on functional protein association networks database,the protein-protein interaction network map of intersection targets between Cidan capsules and liver cancer was constructed.The gene ontology bioprocess and Kyoto encyclopedia of genes and genomes signaling pathway enrichment analysis of intersection targets were performed using database for annotation,visualization and integrated discovery.The interactions between key active ingredients and potential target proteins were investigated by molecular docking.Results The Cidan capsules could act on 127 key target proteins such as tumor protein 53,actin and serine/threonine-protein kinase 1 through 59 main active ingredients such as Quercetin,Kaempferol and Luteolin.Then pathways in cancer,phosphatidylinositol 3 kinase-serine/threonine kinase signaling pathway and other tumor-related signaling pathways are regulated to induce cell cycle arrest and apoptosis,thus achieving the purpose of liver cancer treatment.Molecular docking results showed that the main active ingredients in Cidan capsules could well bind to several key core targets with high degree value,which might activate or inhibit the target proteins.Conclusion The potential mechanism of Cidan capsules in the treatment of liver cancer featured multi-components,multi-targets and multi-pathways action.

关 键 词：慈丹胶囊 肝癌 信号通路 网络药理学 作用机制 

分 类 号：R28[医药卫生—中药学]