基于网络药理学与分子对接探讨大陷胸汤治疗急性胰腺炎的作用机制

曾程; 刘同亭

文章摘要

曾程,刘同亭.基于网络药理学与分子对接探讨大陷胸汤治疗急性胰腺炎的作用机制[J].浙江中医药大学学报,2023,47(6):678-690.

基于网络药理学与分子对接探讨大陷胸汤治疗急性胰腺炎的作用机制

Study on the Mechanism of Daxianxiong Decoction in the Treatment of Acute Pancreatitis Based on Network Pharmacology and Molecular Docking

DOI：10.16466/j.issn1005-5509.2023.06.018

中文关键词: 大陷胸汤急性胰腺炎网络药理学分子对接靶点预测信号通路作用机制

英文关键词: Daxianxiong Decoction acute pancreatitis network pharmacology molecular docking target prediction signaling pathway mechanism of action

基金项目:国际特许药械引进与临床应用标准化路径研究项目(HNXJJS220002)

作者	单位
曾程	山东中医药大学第一临床医学院济南 250000
刘同亭	博鳌超级医院

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中文摘要:

[目的] 基于网络药理学与分子对接方法探讨大陷胸汤治疗急性胰腺炎(acute pancreatitis，AP)的药理作用机制。[方法] 为获取大陷胸汤的主要化学成分，在中药系统药理学数据库与分析平台(Traditional Chinese Medicine Database and Analysis Platform，TCMSP)数据库、中医药百科全书(Encyclopedia of Traditional Chinese Medicine，ETCM)数据库、化学专业数据库进行检索并筛选潜在有效化合物，通过Swiss Target Prediction数据库对潜在有效成分进行靶点预测；使用人类基因数据库(Human Gene Database，GeneCards)、在线人类孟德尔遗传数据库(Online Mendelian Inheritance in Man，OMIM)、DisGeNet数据库、DrugBank数据库获取疾病目标靶点；结合STRING平台获取蛋白互作网络，并对关键靶点蛋白进行网络拓扑学指标分析；运用Metascape数据平台对成分与靶点参与的生物过程及通路进行分析，获取富集分析结果。使用Cytoscape 3.7.1软件构建成分、靶点与通路三者间的关联网络，最后通过AutoDock进行分子对接验证。[结果] 大陷胸汤中筛选获得70个活性成分，160个作用靶点，1 486个疾病靶点。基因本体(gene ontology，GO)富集分析中生物过程包含细胞对氮化合物的反应、肽反应、激酶活性调节、丝裂原活化蛋白激酶(mitogen-activated protein kinase，MAPK)级联调节等；京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes，KEGG)富集分析显示关键通路为磷脂酰肌醇3激酶-蛋白激酶B(phosphatidylinositol 3 kinase-protein kinase B，PI3K-AKT)信号通路、表皮生长因子受体酪氨酸激酶抑制剂耐药(epidermal growth factor receptor tyrosine kinase inhibitor resistance，EGFR tyrosine kinase inhibitor resistance)信号通路、糖尿病并发症中的晚期糖基化终产物及其受体(advanced glycation end products-receptor of advanced glycation end products，AGE-RAGE)信号通路等，其功能主要为参与炎症反应与激酶活性调节，细胞稳态调节及细胞的增殖调控。分子对接结果显示，大部分核心靶点与主要成分之间结合活性良好。[结论] 大陷胸汤干预AP的作用机制呈现成分、靶点、通路的多层级协同，其作用机制可能与大陷胸汤的活性成分对PI3K-AKT信号通路、EGFR酪氨酸激酶抑制剂耐药信号通路及AGE-RAGE信号通路等产生协同调控作用有关。

英文摘要:

[Objective] To explore the pharmacological mechanism of action of Daxianxiong Decoction in the treatment of acute pancreatitis (AP) based on network pharmacology and molecular docking methods. [Methods] In order to obtain the main chemical components of Daxianxiong Decoction， the potentially active compounds were searched and screened in the Traditional Chinese Medicine Database and Analysis Platform(TCMSP) database， the Encyclopedia of Traditional Chinese Medicine(ETCM) database， and specialized chemical databases， and target prediction was performed on the Swiss Target Prediction database. The targets of diseases were obtained using Human Gene Database(GeneCards)， Online Mendelian Inheritance in Man(OMIM)， DisGeNet database and DrugBank database; the protein interaction network was obtained by combining with STRING platform， and the network topology indexes were analyzed for key target proteins; the Metascape data platform was used to analyze the biological processes and pathways involved in the components and targets to obtain enrichment analysis results. The network was constructed using Cytoscape 3.7.1 software， and finally validated by molecular docking with AutoDock. [Results] Seventy active ingredients，160 targets of action and 1 486 disease targets were obtained from the screening of Daxianxiong Decoction. The biological processes in the gene ontology (GO) enrichment analysis included cellular responses to nitrogen compounds， peptide responses， regulation of kinase activity， and regulation of mitogen-activated protein kinase (MAPK) cascade; the Kyoto Encyclopedia of Genes and Genomes(KEGG) showed that the key pathways were phosphatidylinositol 3 kinase-protein kinase B(PI3K-AKT) signaling pathway， epidermal growth factor receptor tyrosine kinase inhibitor resistance(EGFR tyrosine kinase inhibitor resistance) signaling pathway， advanced glycation end products-receptor of advanced glycation end products(AGE-RAGE) signaling pathway in diabetic complications， whose functions were mainly involved in the regulation of inflammatory response and kinase activity， regulation of cellular homeostasis and cell proliferation. The molecular docking results showed that most of the core targets had good binding activity to the main components. [Conclusion] The mechanism of action of Daxianxiong Decoction in intervening AP shows a multi-level synergy of components， targets and pathways， and its mechanism of action may be related to the synergistic modulation of PI3K-AKT signaling pathway， EGFR tyrosine kinase inhibitor resistance signaling pathway and AGE-RAGE signaling pathway by the active components in Daxianxiong Decoction.

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