Objective:To predict the effective components,potential targets and pathways of Simiao Yong’an Decoction in the treatment of lower extremity arteriosclerosis obliterans(ASO)based on the method of network pharmacology...Objective:To predict the effective components,potential targets and pathways of Simiao Yong’an Decoction in the treatment of lower extremity arteriosclerosis obliterans(ASO)based on the method of network pharmacology,and to explore the mechanism of Simiao Yong’an Decoction in treating ASO combined with cell experiment.Methods:TCMSP database was used to screen the active components and targets of Simiao Yong’an decoction,and Genecards and OMIM databases were used to obtain ASO related proteins;PPI network of drug disease target proteins was constructed by string platform;go function and KEGG pathway enrichment of Simiao Yong’an Decoction ASO target were analyzed by David database.The drug target pathway with high correlation with ASO was selected.The model of vascular smooth muscle cell injury(VSMCs)induced by ox LDL was used,and Simiao Yong’an decoction containing pharmaceutical Qing was given to verify the therapeutic effect of Simiao Yong’an Decoction on ox LDL induced VSMCs and its regulation on highly correlated target pathway.Results:A total of 126 active components of Simiao Yong'an Decoction were screened,40 targets of Simiao Yong’an Decoction ASO were selected,99 go biological processes and 48 related signal pathways were related to ASO;the experimental results showed that with the passage of time,Simiao Yongan decoction could significantly inhibit the proliferation of VSMCs(P<0.05);compared with the model group,the percentage of BrdU positive cells in each dose group of Simiao Yong’an decoction was significantly higher than that in the model group In addition,Simiao Yong’an decoction could significantly inhibit the proliferation of VSMCs(P<0.05);in addition,Simiao Yongan decoction could inhibit the levels of IL-6 and IL-1β(P<0.05);significantly inhibit the expression of PCNA,JAK2 and STAT3 mRNA(P<0.05);Conclusions:Simiao Yong’an decoction has the effect of"multi-component,multi-target and multi-channel"in the treatment of ASO.It can inhibit the activation of JAK/STAT signaling pathway,play an anti-inflammatory role and inhibit the proliferation of vascular smooth muscle cells.展开更多
目的:运用网络药理学联合分子对接技术研究四妙勇安汤干预痛风性关节炎的相关靶点与信号通路,探讨四妙勇安汤治疗痛风性关节炎的分子作用机制。方法:在中药系统药理学数据库与分析平台(traditional Chinese medicine systems pharmacolo...目的:运用网络药理学联合分子对接技术研究四妙勇安汤干预痛风性关节炎的相关靶点与信号通路,探讨四妙勇安汤治疗痛风性关节炎的分子作用机制。方法:在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)中筛查出四妙勇安汤组方中的4味中药的活性成分与作用靶点,然后在人类孟德尔遗传综合数据库(online mendelian inheritance in man,OMIM)、GeneCards、PharmGkb、DrugBank和治疗靶点数据库(therapeutic target database,TTD)等数据库中筛选出痛风性关节炎的相关基因靶点,整合后获取药物靶点与疾病靶点的共同交集,并借助Cytoscape 3.7.2软件拓扑出“活性成分-核心靶点”网络图,通过STRING在线数据库平台获取蛋白质-蛋白质相互作用(protein-protein interaction,PPI)网络图,并对所获得的关键靶点采用基因本体(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。通过Autodock 1.5.6软件对药物的主要活性成分及核心作用靶点进行分子对接匹配验证。结果:筛选得到四妙勇安汤干预痛风性关节炎的活性成分96个,靶点38个,其中主要活性成分有槲皮素、山柰酚、柚皮苷和木犀草素等,主要靶点为PTGS2、NOS2、PPARG、MAPK14和PTGS1等,PPI网络分析出CXCL8、PTGS2、MAPK3、TNF、IL-1β、CCL2、MAPK1和HMOX1等8个核心靶点。分子对接结果显示,四妙勇安汤的主要活性成分能够与核心靶点结合且展现出较好的亲和力。结论:四妙勇安汤治疗痛风性关节炎具有多途径、多组分和多靶点的机制特征,四妙勇安汤干预痛风性关节炎的潜在作用机制可能与其发挥降解尿酸、下调炎症因子的表达和调节免疫功能等作用相关。展开更多
基金Harbin Science and Technology Bureau Youth reserve talent project(No.2016RAQXJj209,2016RAQXJ157)"Double-First-Class"discipline development support fund of integrated traditional Chinese and Western Medicine(No.HIJSYL004)。
文摘Objective:To predict the effective components,potential targets and pathways of Simiao Yong’an Decoction in the treatment of lower extremity arteriosclerosis obliterans(ASO)based on the method of network pharmacology,and to explore the mechanism of Simiao Yong’an Decoction in treating ASO combined with cell experiment.Methods:TCMSP database was used to screen the active components and targets of Simiao Yong’an decoction,and Genecards and OMIM databases were used to obtain ASO related proteins;PPI network of drug disease target proteins was constructed by string platform;go function and KEGG pathway enrichment of Simiao Yong’an Decoction ASO target were analyzed by David database.The drug target pathway with high correlation with ASO was selected.The model of vascular smooth muscle cell injury(VSMCs)induced by ox LDL was used,and Simiao Yong’an decoction containing pharmaceutical Qing was given to verify the therapeutic effect of Simiao Yong’an Decoction on ox LDL induced VSMCs and its regulation on highly correlated target pathway.Results:A total of 126 active components of Simiao Yong'an Decoction were screened,40 targets of Simiao Yong’an Decoction ASO were selected,99 go biological processes and 48 related signal pathways were related to ASO;the experimental results showed that with the passage of time,Simiao Yongan decoction could significantly inhibit the proliferation of VSMCs(P<0.05);compared with the model group,the percentage of BrdU positive cells in each dose group of Simiao Yong’an decoction was significantly higher than that in the model group In addition,Simiao Yong’an decoction could significantly inhibit the proliferation of VSMCs(P<0.05);in addition,Simiao Yongan decoction could inhibit the levels of IL-6 and IL-1β(P<0.05);significantly inhibit the expression of PCNA,JAK2 and STAT3 mRNA(P<0.05);Conclusions:Simiao Yong’an decoction has the effect of"multi-component,multi-target and multi-channel"in the treatment of ASO.It can inhibit the activation of JAK/STAT signaling pathway,play an anti-inflammatory role and inhibit the proliferation of vascular smooth muscle cells.
文摘目的:运用网络药理学联合分子对接技术研究四妙勇安汤干预痛风性关节炎的相关靶点与信号通路,探讨四妙勇安汤治疗痛风性关节炎的分子作用机制。方法:在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)中筛查出四妙勇安汤组方中的4味中药的活性成分与作用靶点,然后在人类孟德尔遗传综合数据库(online mendelian inheritance in man,OMIM)、GeneCards、PharmGkb、DrugBank和治疗靶点数据库(therapeutic target database,TTD)等数据库中筛选出痛风性关节炎的相关基因靶点,整合后获取药物靶点与疾病靶点的共同交集,并借助Cytoscape 3.7.2软件拓扑出“活性成分-核心靶点”网络图,通过STRING在线数据库平台获取蛋白质-蛋白质相互作用(protein-protein interaction,PPI)网络图,并对所获得的关键靶点采用基因本体(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。通过Autodock 1.5.6软件对药物的主要活性成分及核心作用靶点进行分子对接匹配验证。结果:筛选得到四妙勇安汤干预痛风性关节炎的活性成分96个,靶点38个,其中主要活性成分有槲皮素、山柰酚、柚皮苷和木犀草素等,主要靶点为PTGS2、NOS2、PPARG、MAPK14和PTGS1等,PPI网络分析出CXCL8、PTGS2、MAPK3、TNF、IL-1β、CCL2、MAPK1和HMOX1等8个核心靶点。分子对接结果显示,四妙勇安汤的主要活性成分能够与核心靶点结合且展现出较好的亲和力。结论:四妙勇安汤治疗痛风性关节炎具有多途径、多组分和多靶点的机制特征,四妙勇安汤干预痛风性关节炎的潜在作用机制可能与其发挥降解尿酸、下调炎症因子的表达和调节免疫功能等作用相关。
