Objective:To study the therapeutic effect of Huoxue Tongluo Decoction(HXTLD)on erectile dysfunction caused by ischemic stroke and identify the mechanisms involved.Methods:Network pharmacology was used to predict the k...Objective:To study the therapeutic effect of Huoxue Tongluo Decoction(HXTLD)on erectile dysfunction caused by ischemic stroke and identify the mechanisms involved.Methods:Network pharmacology was used to predict the key active ingredients and targets of HXTLD.Surgical methods were used to create a rat model of ischemic stroke.The rats were then given a suspension of HXTLD by ig administration.Erectile function was evaluated by Apomorphine(APO)induction.Real-time fluorescence quantitative reverse transcription-polymerase chain reaction(Real-time PCR)and Western blotting were used to detect the expression of related m RNAs and proteins in rat penile corpus cavernous tissue and brain tissue.Hematoxylin&Eosin(HE)staining was used to investigate structural changes in the penile cavernous tissue.Results:Network pharmacology showed that tumor necrosis factor(TNF),nitric oxide synthase 3(eNOS),and vascular endothelial growth factor(VEGF)were the key targets of HXTLD in the treatment of erectile dysfunction caused by ischemic stroke.Experimental studies showed that HXTLD improved erectile dysfunction caused by ischemic stroke.HE results showed that HXTLD improved the structure of the corpus cavernosa.HXTLD also inhibited the expression of TNF and VEGF proteins in penile tissue(P<0.05)and enhanced the expression of e NOS protein in penile tissue(P<0.05).Conclusion:HXTLD improved the erectile function of rats with erectile dysfunction caused by ischemic stroke by regulating the m RNA and protein levels of TNF,e NOS and VEGF.展开更多
[目的]基于网络药理学和分子对接方法,挖掘姚乃礼教授健脾祛湿解毒通络方治疗幽门螺杆菌(Helicobacter pylori,Hp)感染的作用机制。[方法]应用中药系统药理学分析平台(Traditional Chinese Medicine Systems Pharmacology,TCMSP),检索...[目的]基于网络药理学和分子对接方法,挖掘姚乃礼教授健脾祛湿解毒通络方治疗幽门螺杆菌(Helicobacter pylori,Hp)感染的作用机制。[方法]应用中药系统药理学分析平台(Traditional Chinese Medicine Systems Pharmacology,TCMSP),检索并获取健脾祛湿解毒通络方药物的活性成分及靶点,通过人类孟德尔遗传在线(Online Mendelian Inheritance in Man,OMIM)、人类基因综合数据库(Human Gene Comprehensive Database,GeneCards)和DrugBank数据库获取Hp感染相关靶点,对药物靶点与疾病靶点取交集,作为健脾祛湿解毒通络方治疗Hp感染的潜在作用靶点。采用Cytoscape 3.7.0软件构建药物-成分-共有靶点网络,通过STRING网站构建蛋白互作(protein protein interaction,PPI)网络,通过Metascape平台进行基因本体(gene ontology,GO)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。利用AutoDock软件,对核心靶点和度值前5位的主要活性成分进行分子对接。[结果]健脾祛湿解毒通络方治疗Hp感染有126个靶点,涉及118个活性成分,Cytoscape 3.7.0软件筛选出槲皮素、β-谷甾醇、金合欢素、山柰酚、豆甾醇等主要活性成分,PPI网络分析后得到肿瘤蛋白P53(tumor protein p53,TP53)、信号转导和转录激活因子3(signal transducer and activator of transcription 3,STAT3)、转录因子p65(transcription factor p65,RELA)、丝裂原活化蛋白激酶3(mitogen-activated protein kinase 3,MAPK3)、酪氨酸蛋白激酶B1(threonine protein kinase B1,AKT1)、MAPK1、肿瘤坏死因子(tumor necrosis factor,TNF)、白细胞介素-6(interleukin-6,IL-6)等核心靶点,参与对脂多糖的反应、对外来刺激的反应等生物过程,涉及癌症相关通路、叉头框转录因子O(forkhead box protein O,FOXO)、缺氧诱导因子-1(hypoxia induced factor-1,HIF-1)、核因子-κB(nuclear factor-κB,NF-κB)信号通路等多条通路。分子对接结果表明,健脾祛湿解毒通络方主要活性成分与核心靶点结合能力较强,验证了上述预测结果。[结论]健脾祛湿解毒通络方中多种成分可作用于Hp感染相关靶点,通过多条通路发挥作用,为深入研究健脾祛湿解毒通络方治疗Hp感染提供了参考。展开更多
基金supported by“3+3”Project for the Inheritance of Beijing Traditional Chinese Medicine(No.2016-SZ-C-60)。
文摘Objective:To study the therapeutic effect of Huoxue Tongluo Decoction(HXTLD)on erectile dysfunction caused by ischemic stroke and identify the mechanisms involved.Methods:Network pharmacology was used to predict the key active ingredients and targets of HXTLD.Surgical methods were used to create a rat model of ischemic stroke.The rats were then given a suspension of HXTLD by ig administration.Erectile function was evaluated by Apomorphine(APO)induction.Real-time fluorescence quantitative reverse transcription-polymerase chain reaction(Real-time PCR)and Western blotting were used to detect the expression of related m RNAs and proteins in rat penile corpus cavernous tissue and brain tissue.Hematoxylin&Eosin(HE)staining was used to investigate structural changes in the penile cavernous tissue.Results:Network pharmacology showed that tumor necrosis factor(TNF),nitric oxide synthase 3(eNOS),and vascular endothelial growth factor(VEGF)were the key targets of HXTLD in the treatment of erectile dysfunction caused by ischemic stroke.Experimental studies showed that HXTLD improved erectile dysfunction caused by ischemic stroke.HE results showed that HXTLD improved the structure of the corpus cavernosa.HXTLD also inhibited the expression of TNF and VEGF proteins in penile tissue(P<0.05)and enhanced the expression of e NOS protein in penile tissue(P<0.05).Conclusion:HXTLD improved the erectile function of rats with erectile dysfunction caused by ischemic stroke by regulating the m RNA and protein levels of TNF,e NOS and VEGF.
文摘[目的]基于网络药理学和分子对接方法,挖掘姚乃礼教授健脾祛湿解毒通络方治疗幽门螺杆菌(Helicobacter pylori,Hp)感染的作用机制。[方法]应用中药系统药理学分析平台(Traditional Chinese Medicine Systems Pharmacology,TCMSP),检索并获取健脾祛湿解毒通络方药物的活性成分及靶点,通过人类孟德尔遗传在线(Online Mendelian Inheritance in Man,OMIM)、人类基因综合数据库(Human Gene Comprehensive Database,GeneCards)和DrugBank数据库获取Hp感染相关靶点,对药物靶点与疾病靶点取交集,作为健脾祛湿解毒通络方治疗Hp感染的潜在作用靶点。采用Cytoscape 3.7.0软件构建药物-成分-共有靶点网络,通过STRING网站构建蛋白互作(protein protein interaction,PPI)网络,通过Metascape平台进行基因本体(gene ontology,GO)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。利用AutoDock软件,对核心靶点和度值前5位的主要活性成分进行分子对接。[结果]健脾祛湿解毒通络方治疗Hp感染有126个靶点,涉及118个活性成分,Cytoscape 3.7.0软件筛选出槲皮素、β-谷甾醇、金合欢素、山柰酚、豆甾醇等主要活性成分,PPI网络分析后得到肿瘤蛋白P53(tumor protein p53,TP53)、信号转导和转录激活因子3(signal transducer and activator of transcription 3,STAT3)、转录因子p65(transcription factor p65,RELA)、丝裂原活化蛋白激酶3(mitogen-activated protein kinase 3,MAPK3)、酪氨酸蛋白激酶B1(threonine protein kinase B1,AKT1)、MAPK1、肿瘤坏死因子(tumor necrosis factor,TNF)、白细胞介素-6(interleukin-6,IL-6)等核心靶点,参与对脂多糖的反应、对外来刺激的反应等生物过程,涉及癌症相关通路、叉头框转录因子O(forkhead box protein O,FOXO)、缺氧诱导因子-1(hypoxia induced factor-1,HIF-1)、核因子-κB(nuclear factor-κB,NF-κB)信号通路等多条通路。分子对接结果表明,健脾祛湿解毒通络方主要活性成分与核心靶点结合能力较强,验证了上述预测结果。[结论]健脾祛湿解毒通络方中多种成分可作用于Hp感染相关靶点,通过多条通路发挥作用,为深入研究健脾祛湿解毒通络方治疗Hp感染提供了参考。
