基于网络药理学分析白头翁汤治疗猪腹泻的作用机制
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摘要
试验利用网络药理学研究方法尝试揭示白头翁汤治疗猪腹泻的活性成分、作用靶点及其基因功能、信号通路的机制。首先在中药系统药理学分析数据库中检索白头翁汤的所有化学成分、作用靶点,进而利用STRING、DAVID、NCBI数据库,Cytoscape软件构建化合物—靶点网络、蛋白质—蛋白质相互作用(PPI)网络、靶点—通路网络,研究白头翁汤治疗猪腹泻的作用机制。通过化合物的口服利用度和类药性筛选得出白头翁汤11个活性化合物,化合物—靶点网络结果显示,11个活性化合物含有63个相应靶点;白头翁汤作用于猪腹泻的PPI网络图包含45个靶点,主要靶点是雌激素受体1(estrogen receptor,ESR1)、CREB结合蛋白(CREB binding protein,CREBBP)、丝裂原活化蛋白激酶1(mitogen-activated protein kinase 1,MAPK1)、雄激素受体(androgen receptor,AR)等,与猪腹泻靶点基因直接相关的靶点是拓扑异构酶Ⅱβ(DNA topoisomeraseⅡ,TOP2B)、ESR1、ESR2、糖皮质激素受体(glucocorticoid receptor,NR3C1)、AR和细胞核受体共激活剂2(nuclear receptor coactivator 2,NCOA2);白头翁汤—猪腹泻PPI网络图关键靶点GO富集条目为5个,其中生物过程、分子功能、细胞组成相关的条目分别有3、1、1个;白头翁汤作用于猪腹泻PPI网络图KEGG信号通路有1条。白头翁汤可能主要通过金鱼草素、掌叶防己碱、8-异戊烯基二氢茆酚-7-葡糖苷、延胡索乙素、足叶草脂素、黄麻苷和8-羟基松脂醇等调控TOP2B、ESR1、ESR2、NR3C1、AR和NCOA2等靶点,基因功能富集于磷脂酶C激活G蛋白偶联受体信号通路、腺苷酸环化酶激活肾上腺素能受体信号通路、DNA模板转录、类固醇结合、细胞膜的组成部分,以及通过KEGG信号通路中神经活性的配体—受体相互作用信号通路来治疗猪腹泻。
In the study,the network pharmacology method was used to reveal the mechanism of Baitouweng decoction in treating swine diarrhea with the active ingredient and target,gene function and signal pathway.All the chemical compounds and targets of Baitouweng decoction were searched in the pharmacological analysis database of traditional Chinese medicine(TCM).Then the compound-target network,protein-protein interaction(PPI)network and target-pathway net-work were constructed by STRING,DAVID,NCBI databases and Cytoscape software to study the mechanism of Baitouweng decoction in treating swine diarrhea.The results showed that 11 active compounds of Baitouweng decoction were screened through the oral availability and drug-likeness,and the results of compound-target network showed that there were 63 corresponding targets corresponding to 11 compounds.The Baitouweng decoction-swine diarrhea PPI network diagram contained 45 targets,in which the key targets were ESR1,CREBBP,MAPK1,AR and so on,TOP2 B,ESR1,ESR2,NR3 C1,AR and NCOA2 were directly related to the targets of swine diarrhea.There were 2 KEGG pathways and 5 gene ontology(GO)entries of which the number of biological process,molecular function and cellular component was 3,1 and 1,respectively.Baitouweng decoction could regulate the expression of TOP2 B,ESR1,ESR2,NR3 C1,AR and NCOA2 and other regulated genes by aureusidin,palmatine,corylifol C,fumarine,peltatin,capsularin and8-hydroxypinoresinol.The phospholipase C activation G protein-coupled receptor signaling pathway,adenylate cyclase-activating adrenergic receptor signaling pathway,DNA template transcription,steroid binding,and cell membrane components were used to treat swine diarrhea through neuroactive ligand-receptor interaction signaling pathways.
In the study,the network pharmacology method was used to reveal the mechanism of Baitouweng decoction in treating swine diarrhea with the active ingredient and target,gene function and signal pathway.All the chemical compounds and targets of Baitouweng decoction were searched in the pharmacological analysis database of traditional Chinese medicine(TCM).Then the compound-target network,protein-protein interaction(PPI)network and target-pathway net-work were constructed by STRING,DAVID,NCBI databases and Cytoscape software to study the mechanism of Baitouweng decoction in treating swine diarrhea.The results showed that 11 active compounds of Baitouweng decoction were screened through the oral availability and drug-likeness,and the results of compound-target network showed that there were 63 corresponding targets corresponding to 11 compounds.The Baitouweng decoction-swine diarrhea PPI network diagram contained 45 targets,in which the key targets were ESR1,CREBBP,MAPK1,AR and so on,TOP2 B,ESR1,ESR2,NR3 C1,AR and NCOA2 were directly related to the targets of swine diarrhea.There were 2 KEGG pathways and 5 gene ontology(GO)entries of which the number of biological process,molecular function and cellular component was 3,1 and 1,respectively.Baitouweng decoction could regulate the expression of TOP2 B,ESR1,ESR2,NR3 C1,AR and NCOA2 and other regulated genes by aureusidin,palmatine,corylifol C,fumarine,peltatin,capsularin and8-hydroxypinoresinol.The phospholipase C activation G protein-coupled receptor signaling pathway,adenylate cyclase-activating adrenergic receptor signaling pathway,DNA template transcription,steroid binding,and cell membrane components were used to treat swine diarrhea through neuroactive ligand-receptor interaction signaling pathways.
引文
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