中国药物警戒 ›› 2021, Vol. 18 ›› Issue (10): 930-935.
DOI: 10.19803/j.1672-8629.2021.10.07

• 基础与临床研究 • 上一篇    下一篇

基于网络药理学的八珍汤治疗免疫性血小板减少症的作用机制

黄伟1,2, 罗雅琴, 王晓1,*   

  1. 1齐鲁工业大学(山东省科学院)山东省分析测试中心,山东 济南 250014;
    2山东省中医药研究院,山东 济南 250014;
    3山东中医药大学附属医院,山东 济南 250014
  • 收稿日期:2020-06-28 出版日期:2021-10-15 发布日期:2021-10-27
  • 通讯作者: *王晓,男,博士,研究员·博导,中药资源与药效物质基础。E-mail:wxjn1998@126.com
  • 作者简介:黄伟,男,博士,副研究员,中药药效物质基础及作用机理。为并列第一作者。
  • 基金资助:
    国家自然科学基金资助项目(81704029); 齐鲁卫生与健康杰出青年人才资助项目(鲁卫人才字[2020] 3号); 中央本级重大增减支项目“名贵中药资源可持续利用能力建设项目”(2060302); 全国名老中医药专家刘持年传承工作室建设项目(国中医药人教发[2014] 20号); 山东省中医药科技面上项目(2020M027)

The Mechanism of Bazhen Decoction in Treating Immune Thrombocytopenia Based on Network Pharmacology

HUANG Wei1,2, LUO Yaqin, WANG Xiao1*   

  1. 1Qilu University of Technology, (Shandong Academy of Sciences) Shandong Analysis and Test Center, Jinan Shandong 250014, China;
    2Shandong Academy of Chinese Medicine, Jinan Shandong 250014, China;
    3The Affiliated Hospital of Shandong University of Chinese Medicine, Jinan Shandong 250014, China
  • Received:2020-06-28 Online:2021-10-15 Published:2021-10-27

摘要: 目的 利用网络药理学探讨八珍汤治疗免疫性血小板减少症(ITP)的作用机制。方法 利用中药系统药理学数据库与分析平台(TCMSP)进行八珍汤主要活性成分的筛选,Drugbank数据库进行靶点预测, 应用Cytoscape 3.7.1软件构建化学成分-靶点网络;人类孟德尔遗传数据库(OMIM)、人类基因数据库(Gene Cards)、Drugbank获得ITP的相关靶基因,将药物活性成分靶点与ITP靶点相映射,获得交集靶点,即八珍汤作用于ITP的预测靶点。利用STRING数据库在线构建交集靶点蛋白相互作用网络(PPI),筛选出关键靶点基因。利用DAVID 6. 8和微生信在线工具对交集靶点进行基因本体(GO)分析和基于京都基因与基因组百科全书(KEGG)通路富集分析。结果 研究显示共挖掘到八珍汤中160种化学成分及247个潜在靶点,ITP疾病304个相关靶点,得到八珍汤-疾病共同靶点20个。槲皮素(quercetin)、山奈酚(kaempferol)和7-甲氧基-2-甲基异黄酮(7-methoxy-2-methyl isoflavone)调节与ITP有关的大多数靶标。GO生物功能分析显示,主要涉及蛋白质磷酸化、细胞凋亡过程、信号转导、增殖等生物过程。KEGG通路富集结果显示,八珍汤治疗ITP潜在基因的通路主要涉及PI3K-Akt信号通路、Ras信号通路、胰岛素信号通路、FoxO 信号通路、MAPK信号通路、小G蛋白Rap1信号通路、T细胞受体信号通路等。结论 八珍汤治疗ITP是通过多成分、多靶点、多通路的复杂机制来发挥作用的,其核心靶点是RAF1、PIK3CG、IKBKB、MAPK10、EGFR、GSK3B、MAPK14等基因,调控机制主要涉及免疫调节、信号转导及相关信号通路中的蛋白聚糖调节等。

关键词: 八珍汤, 免疫性血小板减少症, 网络药理学, 作用机制

Abstract: Objective To explore the mechanism by which Bazhen Decoction combats immune thrombocytopenia (ITP) using network pharmacology. Methods The main active ingredients of Bazhen Decoction were screened using the pharmacological database and analysis platform (TCMSP) of the Chinese Medicine System. Drugbank database was searched for target prediction. Cytoscape 3.7.1 software was used to build a chemical composition-target network. Online Mendelian Inheritance In Man (OMIM), human gene database (Gene Cards), and Drugbank were searched for the related target genes of ITP.The target of active ingredients of the drug was mapped to the ITP target to obtain the intersection target, which was the predicted target for ITP of Bazhen Decoration. The STRING database was used to construct an online intersection target protein interaction network (PPI) to screen out key target genes. Gene ontology (GO) analysis and enrichment analysis based on the Kyoto Encyclopedia of Genes and Genomes (KEGG) were used to analyze intersection targets using DAVID 6.8 and online tools. Results A total of 160 chemical components, 247 potential targets, 304 ITP-related targets, and 20 common targets were found in Bazhen Decoration. Quercetin, kaempferol, and 7-Methoxy-2-methyl isoflavone regulated most of the targets associated with ITP. GO biological function analysis showed that this decoration was involved in such biological processes as protein phosphorylation, apoptosis, signal transduction, and proliferation. The enrichment results of KEGG pathway showed that the potential pathways through which Bazhen Decoration could treat ITP included PI3K-Akt signaling pathway, Ras signaling pathway, insulin signaling pathway, FoxO signaling pathway, MAPK signaling pathway, Rap1 signaling pathway, and T cell receptor signaling pathway. Conclusion Bazhen Decoction can combat ITP through the complex mechanism of multiple components, multiple targets and multiple pathways. The core targets are RAF1, PIK3CG, IKBKB, MAPK10, EGFR, GSK3B, and MAPK14. The regulatory mechanism mainly involves immune regulation, signal transduction and proteoglycan regulation in related signaling pathways.

Key words: Bazhen Decoction, immune thrombocytopenia (ITP), network pharmacology, mechanism

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