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基于网络药理学与分子对接研究四逆散治疗肝癌的作用机制
Mechanism of action of Sini powder in treatment of liver cancer based on network pharmacology and molecular docking
文章发布日期:2020年08月22日  来源:  作者:李菁,莫嘉浩,许洪彬,等  点击次数:607次  下载次数:35次

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【摘要】:目的 联合网络药理学-分子对接研究四逆散治疗肝癌的作用机制。方法 运用中药系统药理学数据库和分析平台(TCMSP)获取四逆散的化合物及靶标,通过Uniprot获取对应的基因Symbol;从人类基因数据库获取肝癌的疾病基因,并筛选出与四逆散靶标基因的交集基因;运用Cytoscape3.7.1软件绘制“中药-化合物-治疗靶标”网络图;运用STRING构建蛋白质相互作用(PPI)网络、R studio软件对治疗靶标进行GO和KEGG富集分析,并对结果进行可视化;选择靶点数目最多的活性成分作为配体,PPI网络中度值(Degree)最大的靶点作为受体,预测受体-配体复合物结构与相互结合的氨基酸残基。结果 研究筛选得到四逆散治疗肝癌核心靶标91个,相关活性成分141种,其中槲皮素、山柰酚等为四逆散治疗肝癌的主要活性成分;TP53、HSP90AA1等是治疗主要作用靶标;GO富集分析后共获得符合筛选标准的条目1007条,主要涉及抗氧化反应、蛋白丝氨酸-苏氨酸激酶活性调控、细胞应激反应等多个生物过程,KEGG富集分析共获得102条,主要调控乙型肝炎通路、PI3K-Akt信号通路以防治肝癌,分子对接结果验证槲皮素-TP53的VAL147、CYS220、GLU221、PRO222等晶体结构域的协同抗癌效应。结论 本研究揭示了四逆散作用于多靶点、多信号通路治疗肝癌的作用机制,为生物实验提供理论基础。
【Abstract】:Objective To investigate the mechanism of action of Sini powder in the treatment of liver cancer based on network pharmacology and molecular docking. Methods Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform was used to obtain the compound and target of Sini powder, and the corresponding gene Symbol was obtained through Uniprot. The disease genes of liver cancer were obtained from Human Genome Database, and the genes with intersection with the target genes of Sini powder were screened out. Cytoscape3.7.1 software was used to draw the map of “traditional Chinese medicine (TCM)-compound-target” network. STRING was used to construct a protein-protein interaction (PPI) network, R studio software was used to conduct gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses on therapeutic targets, and then the results were visualized. The active component with the highest number of targets was selected as the ligand, and the target with the highest degree in the PPI network was selected as the receptor, so as to predict the structure of receptor-ligand complex and the amino acid residues that bind to each other. Results In this study, 91 core targets and 141 relevant active components of Sini powder were screened out, among which quercetin and kaempferol were the main active components in the treatment of liver cancer. TP53 and HSP90AA1 were the main therapeutic targets. The GO enrichment analysis obtained 1007 items which met the screening criteria, which were mainly involved in the biological processes of antioxidation reaction, activity regulation of protein serine and threonine kinase, and cellular stress response. The KEGG enrichment analysis obtained 102 pathways, which mainly regulated the hepatitis B pathway and the PI3K-Akt signaling pathway in the prevention and treatment of liver cancer. The results of molecular docking showed a synergistic antitumor effect between the crystal structure domains VAL147, CYS220, GLU221, and PRO222 of quercetin-TP53. Conclusion This study reveals the mechanism of action of Sini powder in the treatment of liver cancer by acting on multiple targets and signaling pathways, which provides a theoretical basis for biological experiments.
【关键字】:四逆散; 肝肿瘤; 分子对接模拟; 网络药理学
【Key words】:Sini powders; liver neoplasms; molecular docking simulation; network pharmacology
【引证本文】:LI J, MO JH, XU HB, et al. Mechanism of action of Sini powder in treatment of liver cancer based on network pharmacology and molecular docking[J]. J Clin Hepatol, 2020, 36(9): 1998-2004. (in Chinese)
李菁, 莫嘉浩, 许洪彬, 等. 基于网络药理学与分子对接研究四逆散治疗肝癌的作用机制[J]. 临床肝胆病杂志, 2020, 36(9): 1998-2004.

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