维血宁颗粒治疗免疫性血小板减少症的网络药理作用机制研究

doi:10.19803/j.1672-8629.2021.11.11

中国药物警戒 ›› 2021, Vol. 18 ›› Issue (11): 1048-1054.
DOI: 10.19803/j.1672-8629.2021.11.11

维血宁颗粒治疗免疫性血小板减少症的网络药理作用机制研究

黄伟^1,2, 罗雅琴, 王晓^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:2020-09-18 发布日期:2021-11-18
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研究。E-mail：wxjn1998@126.com
作者简介:黄伟,男,博士后,副研究员,中药药效物质基础研究。^#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）

Network Pharmacological Mechanisms of Weixuening Granules in the Treatment of Immune Thrombocytopenia

HUANG Wei^1,2, LUO Yaqin, WANG Xiao^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:2020-09-18 Published:2021-11-18

摘要/Abstract

摘要： 目的利用网络药理学探讨维血宁颗粒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）进行维血宁颗粒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,即维血宁颗粒作用于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）,采用Cyt-oscape 3.7.1软件中的CytoHubba和MCODE插件筛选出关键靶点基因。利用DAVID 6. 8和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维血宁颗粒中64种化学成分及229个潜在靶点,ITP疾病1 746个相关靶点,得到维血宁颗粒-ITP疾病共同靶点120个。槲皮素（quercetin）、山柰酚（kaempferol）和木犀草素（luteolin）调节与ITP有关的大多数靶标,分别为147、60和56个靶标。GO生物功能分析显示,主要涉及RNA聚合酶II启动子转录、凋亡、炎症、衰老、细胞增殖、信号转导等生物过程。 KEGG通路富集结果显示118条信号通路,主要涉及癌症途径（pathways in cancer）、乙型肝炎（Hepatitis B）、PI3K-Akt信号通路（PI3K-Akt signaling pathway）等。结论维血宁颗粒治疗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TP53、AKT1、VEGFA、CASP3、IL6、JUN、TNF、MAPK1、MYC、STAT3等基因,调控机制主要涉及炎症、免疫调节及相关信号转导通路调节等。该研究初步揭示了维血宁颗粒通过多成分-多靶点-多通路治疗免疫性血小板减少症的作用机制,为维血宁颗粒的机制研究提供理论依据。

关键词: 维血宁颗粒, 免疫性血小板减少症, 网络药理学, 作用机制

Abstract: Objectiv e To explore the mechanism of Weixuening granules in the treatment of immune thrombocytopenia (ITP) using network pharmacology. Methods The main active ingredients of Weixuening granules were screened using the pharmacological database and analysis platform (TCMSP) of the Chinese Medicine System. Drugbank database was used for target prediction, while Cytoscape 3.7.1 software was used to build a chemical composition-target network. Online Mendelian Inheritance in Man (OMIM), the Human Gene Database (Gene Cards), and Drugbank were searched for the related target genes of ITP. The targets of active ingredients of drugs were mapped to the ITP targets to obtain the intersection targets, which were the predicted targets for ITP of Weixuening granules. The STRING database was used to construct an intersection target protein interaction network (PPI) online before the CytoHubba and MCODE plug-ins in the Cytoscape 3.7.1 software were used 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 64 chemical components and 229 potential targets in Weixuening granules, 1 746 related targets in ITP disease, and 120 common targets in Weixuening granules- ITP disease were found. Quercetin, kaempferol, and luteolin regulated most of the targets associated with ITP, involving 47, 60 and 56 targets respectively. GO biological function analysis showed that such biological processes were involved as RNA polymerase II promoter, apoptosis, inflammation, aging, cell proliferation and signal transduction. KEGG pathway enrichment results showed 118 signaling pathways, mainly related to pathways in cancer, hepatitis B, and PI3K-Akt signaling pathway. Conclusion Weixuening granules combat ITP by the complex mechanism of multiple components, multiple targets and multiple pathways. The core targets are TP53, AKT1, VEGFA, CASP3, IL6, JUN, TNF, MAPK1, MYC and STAT3. The regulation mechanism involves regulation of inflammation, immunity and related signal transduction pathways.

Key words: Weixuening granules, immune thrombocytopenia (ITP), network pharmacology, mechanism

中图分类号:

R965

黄伟, 罗雅琴, 王晓. 维血宁颗粒治疗免疫性血小板减少症的网络药理作用机制研究[J]. 中国药物警戒, 2021, 18(11): 1048-1054.

HUANG Wei, LUO Yaqin, WANG Xiao. Network Pharmacological Mechanisms of Weixuening Granules in the Treatment of Immune Thrombocytopenia[J]. Chinese Journal of Pharmacovigilance, 2021, 18(11): 1048-1054.

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维血宁颗粒治疗免疫性血小板减少症的网络药理作用机制研究

Network Pharmacological Mechanisms of Weixuening Granules in the Treatment of Immune Thrombocytopenia

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