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天津中医药大学第一附属医院消化科国家中医针灸临床医学研究中心
纸质出版日期:2021,
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赵帅, 周正华. 青赤散保留灌肠治疗左半结肠型溃疡性结肠炎的网络药理学研究[J]. 中国医院用药评价与分析, 2021,21(12):1425-1433.
ZHAO Shuai, ZHOU Zhenghua. Network Pharmacology of Retention Enema with Green and Red Powder in the Treatment of Ulcerative Colitis of Left Colon Type[J]. 2021,21(12):1425-1433.
赵帅, 周正华. 青赤散保留灌肠治疗左半结肠型溃疡性结肠炎的网络药理学研究[J]. 中国医院用药评价与分析, 2021,21(12):1425-1433. DOI: 10.14009/j.issn.1672-2124.2021.12.002.
ZHAO Shuai, ZHOU Zhenghua. Network Pharmacology of Retention Enema with Green and Red Powder in the Treatment of Ulcerative Colitis of Left Colon Type[J]. 2021,21(12):1425-1433. DOI: 10.14009/j.issn.1672-2124.2021.12.002.
目的:运用网络药理学方法及分子对接技术
探讨青赤散保留灌肠治疗左半结肠型溃疡性结肠炎(ulcerative colitis
UC)的作用机制。方法:利用中药系统药理学数据库与分析平台(traditional Chinese medicine systems pharmacology database and analysis platform
TCMSP)、Pub Chem、STITCH数据库及文献
检索、筛选青赤散的活性成分并预测作用靶点
与Gene Cards、Drugbank和人类孟德尔遗传综合数据库(online mendelian inheritance in man
OMIM)等数据库获取的UC靶点取交集。借助Cytoscape 3.7.2软件进行"药物-成分-靶点"网络构建并筛选主要活性成分。采用String 11.0平台输出蛋白质-蛋白质相互作用(protein-protein Interaction
PPI)网络并筛选核心靶点。利用Metascape数据库对核心靶点进行基因本体(gene ontology
GO)功能富集分析和京都基因与基因组百科全书(Kyoto encyclopedia of genes and genomes
KEGG)通路富集分析。将活性成分、核心靶点、关键通路相互关联
运用Cytoscape 3.7. 2软件绘制网络图。利用Schr9dinger软件完成分子对接。结果:筛选得到青赤散活性成分69种
主要活性成分10种
包含槲皮素、山柰酚、木犀草素、β-谷甾醇、刺芒柄花素、豆甾醇、靛玉红和卡文定碱等
作用靶点206个
与UC相关靶点142个
筛选核心靶点27个
包括AKT1、TP53、IL-6、MAPK3和TNF等
主要作用于MAPK、IL-17、PI3K/Akt、TNF、TOLL样受体、细胞凋亡和EBV感染等信号通路
发挥截断炎症反应、维护黏膜屏障、改善肠道血供、平衡自身免疫、调整肠道菌群和抗病毒感染等功能
且分子对接结果表明主要活性成分与核心靶点蛋白的结合性良好。结论:青赤散通过多成分、多靶点、多通路参与UC的治疗过程
可为进一步的基础研究和临床研究提供客观依据
为UC外用药的研发探索新思路。
OBJECTIVE: To explore the mechanism of retention enema with green and red powder in the treatment of ulcerative colitis( UC) of left colon type by network pharmacology and molecular docking techniques. METHODS:Traditional Chinese medicine systems pharmacology database and analysis platform( TCMSP)
Pub Chem
STITCH database and literature search were used to screen the active components of retention enema with green and red powder and predict the action target. And the intersection was obtained with UC targets obtained from Gene Cards
Drugbank and online mendelian inheritance in man( OMIM) database. Cytoscape 3. 7. 2 software was used to construct the “drugcomponent-target”network and screen the main active components. String 11. 0 platform was used to output the proteinprotein interaction( PPI) network and screen the core targets. Gene ontology( GO) functional enrichment analysis and Kyoto encyclopedia of genes and genomes( KEGG) pathway enrichment analysis were performed on the core targets by using Metascape genomes database. The active components
core targets and key pathways were correlated with each other
and the network diagram was drawn by using Cytoscape 3. 7. 2 software. Schr9 dinger software was used to complete the molecular docking. RESULTS: Sixty-nine kinds of active components were obtained
including 10 main active components
including quercetin
kaempferol
luteolin
β-sitosterol
formononetin
stigmasterol
indiyured and carbendine. There were 206 targets
including 142 targets related to UC and 27 core targets with AKT1
TP53
IL-6
MAPK3 and TNF
mainly acting on MAPK
IL-17
PI3K/Akt
TNF
Toll-like receptor
apoptosis and EBV infection and other signaling pathways
which could play the functions of intercepting the inflammatory response
maintaining the mucosal barrier
improving the intestinal blood supply
balancing the autoimmunity
adjusting the intestinal flora and antiviral infection. And the molecular docking results showed that the main active components bound well to the core target proteins. CONCLUSIONS: Retention enema with green and red powder in the treatment of UC through multiple components
multiple targets and multiple pathways
which provides an objective basis for further basic and clinical research and explores new ideas for the development of external medication of UC.
网络药理学青赤散溃疡性结肠炎
Network pharmacologyRetention enema with green and red powderUlcerative colitis
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