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 Beijing 100029,China.
Zhongguo Zhong Yao Za Zhi. 2019 Dec;44(24):5465-5472. doi: 10.19540/j.cnki.cjcmm.20190929.402.
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.
本文旨在通过网络药理学方法筛选荆芥和防风治疗溃疡性结肠炎的活性靶点，并探讨其作用机制。通过中药系统药理学（TCMSP）数据库筛选荆芥和防风的有效成分，选取口服生物利用度（OB）≥30%和类药性（DL）≥18%作为阈值。构建主要成分与其对应靶点之间的靶点蛋白相互作用（PPI）网络。从Uniprot数据库获得与药物靶点位点对应的182个人类基因；从Genecard数据库获得与溃疡性结肠炎对应的3874个基因。从疾病基因和药物基因中筛选出115个交集基因，并使用String工具进行PPI相互作用分析。利用Cytoscape软件绘制疾病-靶点PPI网络，并构建成分-靶点-疾病网络。发现108个节点和1882条连接，然后使用Cytoscape软件合并网络并筛选核心网络进行基因GO功能分析和KEGG通路富集分析。随后通过动物实验验证荆芥和防风的作用机制。基因GO功能分析表明涉及生物过程、分子功能和细胞成分，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通路富集分析表明，溃疡性结肠炎的机制可能与肿瘤坏死因子（TNF）和Toll样受体（TLRs）信号通路介导的细胞炎性因子白细胞介素-1（IL-1）和白细胞介素-6（IL-6）有关。荆芥和防风有效成分治疗溃疡性结肠炎的可能机制可能与干预TNF和TLRs信号通路的细胞因子受体结合、减少核因子-κB（NF-κB）的转录以及抑制肠道炎性因子IL-1和IL-6的分泌有关。
