文献类型：期刊文献

中文题名：基于网络药理学探讨小儿开胃增食合剂治疗小儿厌食症的潜在作用机制

英文题名：Based on Network Pharmacology to Explore the Potential Mechanism of Xiaoer Kaiwei Zengshi Mixture(小儿开胃增食合剂)in the Treatment of Infantile Anorexia

作者：杨楠[1];田文霞[1];李玉霞[1]

第一作者：杨楠

机构：[1]甘肃中医药大学附属医院,甘肃兰州730020

第一机构：甘肃中医药大学第二附属医院

年份：2022

卷号：36

期号：3

起止页码：1

中文期刊名：实用中医内科杂志

外文期刊名：Journal of Practical Traditional Chinese Internal Medicine

基金：国家自然科学基金青年科学基金项目(81603660);甘肃中医药大学附属医院科研及技术创新(gzfy-2020-21)。

语种：中文

中文关键词：小儿厌食症;小儿开胃增食合剂;网络药理学

外文关键词：pediatric anorexia;Xiaoer Kaiwei Zengshi Mixture Mixture(小儿开胃增食合剂);network pharmacology

摘要：目的基于网络药理学探讨小儿开胃增食合剂治疗小儿厌食症(IA)的潜在作用机制,并对其多成分、多靶点、多通路的机制进行分析。方法以口服生物利用度(OB)≥30%、类药性(DL)≥0.18为筛选条件在TCMSP数据库检索小儿开胃增食合剂的化学成分及预测其作用靶点,并用UniProt数据库对靶点进行校正与转化;在GeneCards、TTD、Drug-Bank数据库检索IA疾病靶点,并用R语言软件进行整合;利用R语言软件筛选药物与IA的共同靶点以作为小儿开胃增食合剂治疗IA的潜在靶点,后采用Cytoscape3.8.3软件构建药物成分-共同靶点互作网络,将共同靶点导入SRTING11.0数据库构建蛋白互作网络(PPI),并运用R语言软件对PPI进行可视化分析;应用R语言软件对共同靶点进行基因本体(GO)分析和京都基因与基因组百科全书(KEGG)通路富集分析。结果检索获得药物活性成分105种,药物成分作用靶点3141个,经UniProt注释后获得药物作用靶点213个;检索疾病靶点共1643个,筛选药物与疾病共同靶点114个,PPI可视化分析发现互作频次较高的靶点主要有信号转导和转录激活因子3(STAT3)、蛋白激酶B(AKT1)、白细胞介素-6(IL-6)、丝裂原活化蛋白激酶1(MAPK1)、丝裂原活化蛋白激酶3(MAPK3)、V-Rel网状内皮增生病毒癌基因同源物A(RELA)、丝裂原活化蛋白激酶14(MAPK14)、雌激素受体1(ESR1)等;GO分析发现共同靶点主要生物学过程有对脂多糖的反应、对细菌起源分子的反应、活性氧代谢过程、对氧化应激的反应、对类固醇激素的反应、对营养水平的反应等;KEGG富集分析发现共同靶点参与的主要信号通路有糖尿病并发症中的AGE-RAGE信号通路、脂质和动脉粥样硬化、白细胞介素-17(IL-17)信号通路、流体剪切应力与动脉粥样硬化、卡波西氏肉瘤相关疱疹病毒感染、TNF信号通路、人巨细胞病毒感染、弓形虫病、C型凝集素受体信号通路等信号通路。结论小儿开胃增食合剂可能具有通过作用于STAT3、JUN、AKT1、IL-6、MAPK1、MAPK3、RELA、MAPK14、ESR1、FOS等关键靶点发挥多成分、多靶点、多通路作用,而抑制炎症反应、调节肠道菌群而改善肠道功能的潜在机制。
Objective Based on the network pharmacology method to predict the potential mechanism of Xiaoer Kaiwei Zengshi Mixture(小儿开胃增食合剂)in the treatment of infantile anorexia(IA),and to explore its multi-component,multi-target,and multi-path mechanism.Methods Using oral bioavailability(OB)≥30%and drug-like properties(DL)≥0.18 as the screening conditions,the TCMSP database was used to retrieve the chemical components of the Xiaoer Kaiwei Zengshi mixture and the targets for predicting its effects,and the Uniprot database was used to check Target correction and transformation;search for IA disease targets in GeneCards,TTD,and DrugBank databases,and integrate them with R language software;use R language software to screen the common target of drugs and IA to be used as the potential of children's appetizer and food mixture to treat IA Then use Cytoscape 3.8.3 software to construct a drug component-common target interaction network,import the common target into the SRTING11.0 database to construct a protein interaction network(PPI),and use R language software to visually analyze the PPI;application R language software performs Gene Ontology(GO)analysis on common targets and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis.Results 105 kinds of drug active ingredients were re-trieved,3141 drug component targets,213 drug targets were obtained after Uniprot annotation;1643 disease targets were retrieved,114 drug and disease common targets were screened,PPI visualization Analysis found that the targets with higher interaction frequency are signal transducer and activator of transcription3(STAT3),protein kinase B(AKT1),interleukin-6(IL-6),mitogen-activated protein kinase 1(MAPK1),Mitogen-activated protein kinase 3(MAPK3),V-Rel reticuloendothelial hyperplasia virus oncogene homolog A(RELA),Mitogen-activated protein kinase 14(MAPK14),estrogen receptor 1(ESR1),etc.;GO analysis found that the main biological processes of the common target include the reaction to lipopolysaccharide,the reaction to the molecules of bacterial origin,the process of reactive oxygen metabolism,the reaction to oxidative stress,the reaction to steroid hormones,the reaction to nutritional levels,etc.;KEGG enrichment analysis found that the main signaling pathways involved in common targets are the AGE-RAGE signaling pathway,lipids and atherosclerosis,IL-17 signaling pathways,fluid shear stress and atherosclerosis,cardinality in diabetic complications.Posey’s sarcoma-related herpes virus infection,TNF signaling pathway,human cytomegalovirus infection,toxoplasmosis,C-type lectin receptor signaling pathway and other signaling pathways.Conclusion Xiaoer Kaiwei Zengshi Mixture may inhibit inflammation by acting on key targets such as STAT3,JUN,AKT1,IL-6,MAPK1,MAPK3,RELA,MAPK14,ESR1,FOS and so on.The potential mechanism of regulating intestinal flora and improving intestinal function.