中国中药杂志

2019, v.44(24) 5465-5472

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荆芥、防风治疗溃疡性结肠炎的网络药理学研究
Network pharmacological study of Schizonepetae Herba and Saposhnikoviae Radix in treatment of ulcerative colitis

屈映;张书信;周璐;傅丽元;刘子号;李诗莹;戴亭亭;杨向阳;姬慧茹;曹敏然;
QU Ying;ZHANG Shu-xin;ZHOU Lu;FU Li-yuan;LIU Zi-hao;LI Shi-ying;DAI Ting-ting;YANG Xiang-yang;JI Hui-ru;CAO Min-ran;Beijing University of Traditional Chinese Medicine;

摘要(Abstract):

对荆芥、防风采用网络药理学方法筛选其治疗溃疡性结肠炎的作用靶点,探讨治疗溃疡性结肠炎作用机制。利用TCMSP数据平台,以口服利用度(OB)≥30%,类药性(DL)≥0. 18为阈值,筛选得到荆芥、防风的主要化学成分,并根据相应的作用靶点,构建靶点PPI网络。利用Uniprot数据库检索中药靶点对应的人类基因182个,从Genecard数据库中检索溃疡性结肠炎对应的基因3 874个,将疾病基因与中药基因取交集共115个,使用String工具对疾病与中药的基因交集进行PPI互作分析。采用Cytoscape软件绘制疾病靶点PPI网络,建立药物成分-靶点基因-疾病关系网络,发现共有108个节点,1 882个连接,并进行网络合并,筛选核心网络,进行基因GO功能和KFGG通路富集分析。采用动物实验进行机制验证。基因GO功能分析提示涉及生物过程、分子功能、细胞组成3个方面,发现溃疡性结肠炎可能与转录因子活性、细胞因子受体结合等有关。基因KEGG通路富集分析发现溃疡性结肠炎发病机制可能与TNF及Toll样受体信号通路介导细胞炎性因子IL-1及IL-6有关。荆芥、防风治疗溃疡性结肠炎机制可能与其有效成分干预TNF信号通路及TLRs信号通路中细胞因子受体结合、降低核转录因子-κB(NF-κB)转录、抑制肠道炎症因子IL-1及IL-6的分泌等具有相关性。
The aim of this paper was to screen the active targets of Schizonepetae Herba and Saposhnikoviae Radix in the treatment of ulcerative colitis by means of network pharmacology,and to investigate their mechanism of action. The effective components of Schizonepetae Herba and Saposhnikoviae Radix were screened out by traditional Chinese medicine systematic pharmacological( TCMSP)database,with oral bioavilability( OB) ≥30% and drug-like( DL) ≥18% selected as the thresholds. Target PPI network was built between the main components and their corresponding targets. One hundred and eighty-two human genes corresponding to the medicine target sites were obtained from Uniprot database; 3 874 genes corresponding to ulcerative colitis were obtained from Genecard database.A total of 115 intersection genes were screened from disease genes and medicine genes,and the PPI interaction analysis was conducted by using String tool. Disease-target PPI network was drawn by using Cytoscape software,and component-target-disease network was constructed. One hundred and eight nodes and 1 882 connections were found,and then Cytoscape software was used to merge the networks and filter the core network for gene GO function analysis and KEGG pathway enrichment analysis. The mechanism of Schizonepetae Herba and Saposhnikoviae Radix was then verified by animal experiment. Gene GO functional analysis suggested that biological process,molecular functions and cell components were involved,and it was found that ulcerative colitis might be related to transcription factor activity,and cytokine receptor binding,etc. Gene KEGG pathway enrichment analysis showed that the mechanism of ulcerative colitis might be associated with TNF and Toll-like receptors( TLRs) signaling pathway-mediated cytoinflammatory factors interleukin-1( IL-1) and interleukin-6( IL6). The possible mechanism of the effective components of Schizonepetae Herba and Saposhnikoviae Radix in treating ulcerative colitis might be related to intervening the cytokine receptor binding of TNF and TLRs signaling pathways,reducing the transcription of nuclear factor-kappaB( NF-κB),and inhibiting the secretion of intestinal inflammatory factors IL-1 and IL-6.

关键词(KeyWords): 荆芥-防风;网络药理学;溃疡性结肠炎;核转录因子-κB(NF-κB)
Schizonepetae Herba-Saposhnikoviae Radix;network pharmacology;ulcerative colitis;nuclear factor-kappa B(NF-kappa B)

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基金项目(Foundation): 国家自然科学基金面上项目(81473689)

作者(Author): 屈映;张书信;周璐;傅丽元;刘子号;李诗莹;戴亭亭;杨向阳;姬慧茹;曹敏然;
QU Ying;ZHANG Shu-xin;ZHOU Lu;FU Li-yuan;LIU Zi-hao;LI Shi-ying;DAI Ting-ting;YANG Xiang-yang;JI Hui-ru;CAO Min-ran;Beijing University of Traditional Chinese Medicine;

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