Objective:The objective of this study is to screen the therapeutic targets of pain of traditional Chinese medicine Chonglou and explore the relevant mechanism by network pharmacology techniques and methods.Materials a...Objective:The objective of this study is to screen the therapeutic targets of pain of traditional Chinese medicine Chonglou and explore the relevant mechanism by network pharmacology techniques and methods.Materials and Methods:The chemical components of Chonglou were collected according to chemistry database and related literature.SwissADME was used to collect the potential active ingredients from all the chemical components of Chonglou and SwissTarget Prediction was utilized to predict their targets.The genes related to pain were collected from GeneCards and Online Mendelian Inheritance in Man databases.Joint genes were uploaded to the online string database for the analysis and the PPI network was constructed.The"Chonglou-active component-target-pain"network was constructed by Cytoscape 3.7.1 software,Gene Ontology(GO)functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis were performed for key target proteins.The top three active components with most targets in the network were docked with the target proteins by the molecular docking technique.Results:A total of nine potential active compounds of Chonglou,264 potential target genes,2385 targets of pain disorder,and 128 common targets for drug and disease were screened.One hundred and thirty-one GO items were identified by the GO enrichment analysis,and 23 related signaling pathways were identified by the KEGG pathway enrichment analysis.Molecular-docking results show that pennogenin is the optimal butt ligand of PIK3 CA,STAT3,mitogen-activated protein kinase 14,and ADORA1.Conclusion:It is preliminarily revealed that Chonglou might treat pain through multiple targets,multiple biology processes and multiple pain-related signaling pathways,providing reference for the subsequent experimental research.展开更多
目的:基于网络药理学探讨重楼-半枝莲药对治疗结肠癌的药效物质基础与潜在分子作用机制。方法:通过中药系统药理学数据库与分析平台(TCMSP)挖掘重楼-半枝莲的主要化学成分,结合SwissTargetPredicion平台筛选出药物活性成分并通过Unipro...目的:基于网络药理学探讨重楼-半枝莲药对治疗结肠癌的药效物质基础与潜在分子作用机制。方法:通过中药系统药理学数据库与分析平台(TCMSP)挖掘重楼-半枝莲的主要化学成分,结合SwissTargetPredicion平台筛选出药物活性成分并通过Uniprot数据库进行靶点预测。通过GeneCards、OMIM和DrugBank数据库检索结肠癌主要作用靶点,利用STRING平台进行蛋白质-蛋白质相互作用分析,制作蛋白质-蛋白质相互作用网络图。再根据David数据库进行基因本体论(GO)分析和京都基因与基因组百科全书(KEGG)通路富集分析,并将富集结果可视化。结果:重楼-半枝莲药对调治结肠癌的活性成分为β-谷甾醇、槲皮素、雄激素受体(Androgen Receptor,AR)等。重楼-半枝莲药对在治疗结肠癌的主要生物通路是癌症信号通路、磷脂酰肌醇3-激酶-蛋白激酶B(Phosphatidylinositol 3-Kinase-Akt,PI3K-Akt)信号通路、丝裂原活化蛋白激酶(Mitogen-Activated Protein Kinase,MAPK)信号通路等。结论:重楼-半枝莲药对治疗结肠癌具有多成分、多靶点、多通路的作用特点,本研究为进一步明确其机制提供了生物信息方面的依据。展开更多
基金financially supported by Natural Science Foundation of China(No.81861138042)Natural Science Foundation of China(No.81673634)+1 种基金Natural Science Foundation of Shandong,China(No.ZR2019MC004)the high-end talent team construction foundation(No.108-10000318)。
文摘Objective:The objective of this study is to screen the therapeutic targets of pain of traditional Chinese medicine Chonglou and explore the relevant mechanism by network pharmacology techniques and methods.Materials and Methods:The chemical components of Chonglou were collected according to chemistry database and related literature.SwissADME was used to collect the potential active ingredients from all the chemical components of Chonglou and SwissTarget Prediction was utilized to predict their targets.The genes related to pain were collected from GeneCards and Online Mendelian Inheritance in Man databases.Joint genes were uploaded to the online string database for the analysis and the PPI network was constructed.The"Chonglou-active component-target-pain"network was constructed by Cytoscape 3.7.1 software,Gene Ontology(GO)functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis were performed for key target proteins.The top three active components with most targets in the network were docked with the target proteins by the molecular docking technique.Results:A total of nine potential active compounds of Chonglou,264 potential target genes,2385 targets of pain disorder,and 128 common targets for drug and disease were screened.One hundred and thirty-one GO items were identified by the GO enrichment analysis,and 23 related signaling pathways were identified by the KEGG pathway enrichment analysis.Molecular-docking results show that pennogenin is the optimal butt ligand of PIK3 CA,STAT3,mitogen-activated protein kinase 14,and ADORA1.Conclusion:It is preliminarily revealed that Chonglou might treat pain through multiple targets,multiple biology processes and multiple pain-related signaling pathways,providing reference for the subsequent experimental research.
文摘目的:基于网络药理学探讨重楼-半枝莲药对治疗结肠癌的药效物质基础与潜在分子作用机制。方法:通过中药系统药理学数据库与分析平台(TCMSP)挖掘重楼-半枝莲的主要化学成分,结合SwissTargetPredicion平台筛选出药物活性成分并通过Uniprot数据库进行靶点预测。通过GeneCards、OMIM和DrugBank数据库检索结肠癌主要作用靶点,利用STRING平台进行蛋白质-蛋白质相互作用分析,制作蛋白质-蛋白质相互作用网络图。再根据David数据库进行基因本体论(GO)分析和京都基因与基因组百科全书(KEGG)通路富集分析,并将富集结果可视化。结果:重楼-半枝莲药对调治结肠癌的活性成分为β-谷甾醇、槲皮素、雄激素受体(Androgen Receptor,AR)等。重楼-半枝莲药对在治疗结肠癌的主要生物通路是癌症信号通路、磷脂酰肌醇3-激酶-蛋白激酶B(Phosphatidylinositol 3-Kinase-Akt,PI3K-Akt)信号通路、丝裂原活化蛋白激酶(Mitogen-Activated Protein Kinase,MAPK)信号通路等。结论:重楼-半枝莲药对治疗结肠癌具有多成分、多靶点、多通路的作用特点,本研究为进一步明确其机制提供了生物信息方面的依据。
文摘目的:观察重楼复方(Chonglou Fufang,CLFF)对小鼠H22肝癌的抑制作用及其免疫调节作用。方法:建立小鼠肝癌H22实体瘤模型,将小鼠随机分为6组:空白对照组、CLFF高、中、低剂量组、环磷酰胺(Cyclo-phosphamide,CTX)组、复方斑蝥(Fufang Banmao,FFBM)组。各组连续灌胃给药10d。于末次给药后24h,断颈处死小鼠,剥离瘤体,无菌条件下取脾脏,分别计算抑瘤率、脾指数,并采用MTT显色法检测药物对细胞毒性T淋巴细胞(Cytotoxic T Lymphocyte,CTL)的细胞不良反应。结果:CLFF显著抑制肿瘤生长,高、中、低剂量组抑瘤率分别为54.84%、54.38%、37.27%,与空白对照组比较具有显著性差异(P<0.01);CLFF高、中、低剂量组脾指数分别为(7.20±3.07)mg/g、(7.23±2.34)mg/g、(10.89±3.91)mg/g,各剂量组与环磷酰胺组比较具有显著性差异(P<0.01),中低剂量组与空白对照组比较具有统计学意义(P<0.05);CLFF高中低剂量组对小鼠的CTL细胞的杀伤率分别为51.76%、44.18%、22.74%,高剂量组与空白对照组及CTX组比较,P<0.05,具有统计学意义。结论:CLFF具有显著抑制肿瘤作用,其抑瘤机制可能与其调节机体的免疫功能有关。
