目的:运用网络药理学和分子对接技术分析运脾泻肺化痰汤治疗支气管哮喘(简称哮喘)的作用机制。方法:通过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)、S...目的:运用网络药理学和分子对接技术分析运脾泻肺化痰汤治疗支气管哮喘(简称哮喘)的作用机制。方法:通过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)、Swiss Target Prediction数据库,检索运脾泻肺化痰汤各中药的有效活性成分及潜在靶点。通过人类基因数据库(the human gene database,GeneCards)、在线人类孟德尔遗传数据库(online mendelian inheritance in man,OMIM)、Drugbank、药物靶标数据库(therapeutic targetdatabase,TTD)、PharmGKB数据库检索“Bronchial asthma”和“Bronchial asthma in children”关键词,获得哮喘的相关靶基因,并与药物有效成分的靶点相映射得到共同靶点。利用Cytoscape 3.8.2构建运脾泻肺化痰汤-活性有效成分-作用靶点-生物学功能网络图,借助STRING数据库构建蛋白互作网络(protein-protein interactions,PPI)。通过Metascape数据库对靶点进行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。结果:运脾泻肺化痰汤与哮喘相关基因取交集后得到288个共同靶点。通过STRING数据库分析得出288个靶点可以发生相互作用,产生了1803条代表蛋白之间相互作用的边,平均自由度为12.5,平均介数为<1.0e-16。推测出运脾泻肺化痰汤治疗哮喘的核心靶点是STAT3、MAPK1、MAPK3、SRC。KEGG通路富集分析结果表明显著富集的通路有176条,其中PI3K/Akt、MAPK、Th17/IL17、TNF、JAK/STAT信号通路等11条可能是运脾泻肺化痰汤治疗哮喘的核心信号通路。分子对接结果表明,运脾泻肺化痰汤中的活性成分与关键靶点具有较高的结合能力。结论:运脾泻肺化痰汤最有可能通过调控PI3K/Akt信号通路治疗哮喘。展开更多
Proliferation and differentiation of intestinal stem cell(ISC)to replace damaged gut mucosal epithelial cells in inflammatory states is a critical step in ameliorating gut inflammation.However,when this disordered pro...Proliferation and differentiation of intestinal stem cell(ISC)to replace damaged gut mucosal epithelial cells in inflammatory states is a critical step in ameliorating gut inflammation.However,when this disordered proliferation continues,it induces the ISC to enter a cancerous state.The gut microbiota on the free surface of the gut mucosal barrier is able to interact with ISC on a sustained basis.Micro-biota metabolites are able to regulate the proliferation of gut stem and progenitor cells through transcription factors,while in steady state,differentiated colono-cytes are able to break down such metabolites,thereby protecting stem cells at the gut crypt.In the future,the gut flora and its metabolites mediating the regulation of ISC differentiation will be a potential treatment for enteropathies.展开更多
文摘目的:运用网络药理学和分子对接技术分析运脾泻肺化痰汤治疗支气管哮喘(简称哮喘)的作用机制。方法:通过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)、Swiss Target Prediction数据库,检索运脾泻肺化痰汤各中药的有效活性成分及潜在靶点。通过人类基因数据库(the human gene database,GeneCards)、在线人类孟德尔遗传数据库(online mendelian inheritance in man,OMIM)、Drugbank、药物靶标数据库(therapeutic targetdatabase,TTD)、PharmGKB数据库检索“Bronchial asthma”和“Bronchial asthma in children”关键词,获得哮喘的相关靶基因,并与药物有效成分的靶点相映射得到共同靶点。利用Cytoscape 3.8.2构建运脾泻肺化痰汤-活性有效成分-作用靶点-生物学功能网络图,借助STRING数据库构建蛋白互作网络(protein-protein interactions,PPI)。通过Metascape数据库对靶点进行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。结果:运脾泻肺化痰汤与哮喘相关基因取交集后得到288个共同靶点。通过STRING数据库分析得出288个靶点可以发生相互作用,产生了1803条代表蛋白之间相互作用的边,平均自由度为12.5,平均介数为<1.0e-16。推测出运脾泻肺化痰汤治疗哮喘的核心靶点是STAT3、MAPK1、MAPK3、SRC。KEGG通路富集分析结果表明显著富集的通路有176条,其中PI3K/Akt、MAPK、Th17/IL17、TNF、JAK/STAT信号通路等11条可能是运脾泻肺化痰汤治疗哮喘的核心信号通路。分子对接结果表明,运脾泻肺化痰汤中的活性成分与关键靶点具有较高的结合能力。结论:运脾泻肺化痰汤最有可能通过调控PI3K/Akt信号通路治疗哮喘。
基金Supported by Scientific Research Fund Project of Education Department of Yunnan Province,No.2023J0346the Kunming Health Commission Kunming Health Science and Technology Personnel Training Project,No.2021-SW-75the Medical and Health Science and Technology Project of Kunming Health Committee,No.2022-03-09-008.
文摘Proliferation and differentiation of intestinal stem cell(ISC)to replace damaged gut mucosal epithelial cells in inflammatory states is a critical step in ameliorating gut inflammation.However,when this disordered proliferation continues,it induces the ISC to enter a cancerous state.The gut microbiota on the free surface of the gut mucosal barrier is able to interact with ISC on a sustained basis.Micro-biota metabolites are able to regulate the proliferation of gut stem and progenitor cells through transcription factors,while in steady state,differentiated colono-cytes are able to break down such metabolites,thereby protecting stem cells at the gut crypt.In the future,the gut flora and its metabolites mediating the regulation of ISC differentiation will be a potential treatment for enteropathies.
