三七主要活性成分作用机制的网络药理学研究
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摘要
目的通过网络药理学研究三七的主要活性成分、作用靶点、相关信号通路和疾病等几方面的关联性,揭示其发挥药效的作用机制。方法从中药系统药理学分析平台(TCMSP)数据库中获得三七的化学成分,并把口服生物利用度(OB)≥30%和类药性(DL)≥0.15作为筛选条件,获得三七的主要活性成分和相关作用靶点。通过UniProt数据库提取作用靶点的基因名称,并用CTD网络在线分析平台获得与靶点相关的疾病和信号通路。最后用Cytoscape 3.6.1构建"活性成分-靶点""靶点-信号通路"和"靶点-疾病"网络图,采用Cytoscape 3.6.1的Network Analyzer插件分析网络图,探讨三七的多重药理作用机制。结果共获得槲皮素、β-谷甾醇、豆甾醇、人参皂苷rh2等9个主要活性成分;这些成分可作用于176个靶点,其主要靶点有PTGS2、PTGS1、HSP90AB1、ER、PDE3A等,这些靶点与肿瘤、高血压、中枢神经系统障碍、自身免疫疾病等45种疾病相关,涵盖癌症、心血管系统、神经系统、免疫系统等几大类疾病。三七的主要活性成分通过作用于靶点而影响相关的信号通路发挥治疗疾病的作用,其影响的信号通路主要包括信号转导通路、免疫通路、Cytokine信号通路、癌症通路等,其中肿瘤、免疫相关的占绝大部分。结论三七是通过多成分、多靶点、多信号通路的协调作用发挥治疗疾病的作用,其中在治疗肿瘤疾病和增强人体免疫力方面具有潜在的优势。
Objective To investigate the main components,action targets,related pathways,diseases,and reveal the multidimensional action pharmacology mechanism of Panax notoginseng based on pharmacology network.Methods The components of Panax notoginseng action targets and were obtained from TCMSP database,and The components with OB≥30% and DL≥0.15 were the main active.The gene names of the targets and the pathways and corresponding diseases related with the targets were extracted from Uniprot database and CTD analysis platform online,respectively.At last,the components-target,target-pathway,and target-disease networks were constructed through Cytoscape 3.6.1,and the networks were analyzed through the Network Analyzer of Cytoscape3.6.1 to study the multidimensional action pharmacology mechanism of Panax notoginseng.Results The 9 active components were obtained,such as quercetin,beta-sitosterol,stigmasterol,ginsenoside rh2.There were 176 targets related with the 9 active components,and the main targets were PTGS2,PTGS1,HSP90 AB1,ER,PDE3 A and so on.Those targets were related with 45 diseases including Cancer,Cardiovascular disease,Nervous system disease,Immune system diseaseand so on.The main active components acted on the targets affecting the corresponding pathways in the treatment of diseases,the pathways influenced by the main components of Panax notoginseng containedPathways in cancer,Signal Transduction,Innate Immune System,and so on,indicating that Panax notoginseng has multiple components,targets,pathways providing synergistic effects in the treatment of diseases.Conclusion The study revealed the main active components of Pueraria lobata and related multidimensional action pharmacology mechanism by pharmacology network,providing the scientific basis for the development and application of Panax notoginseng.
Objective To investigate the main components,action targets,related pathways,diseases,and reveal the multidimensional action pharmacology mechanism of Panax notoginseng based on pharmacology network.Methods The components of Panax notoginseng action targets and were obtained from TCMSP database,and The components with OB≥30% and DL≥0.15 were the main active.The gene names of the targets and the pathways and corresponding diseases related with the targets were extracted from Uniprot database and CTD analysis platform online,respectively.At last,the components-target,target-pathway,and target-disease networks were constructed through Cytoscape 3.6.1,and the networks were analyzed through the Network Analyzer of Cytoscape3.6.1 to study the multidimensional action pharmacology mechanism of Panax notoginseng.Results The 9 active components were obtained,such as quercetin,beta-sitosterol,stigmasterol,ginsenoside rh2.There were 176 targets related with the 9 active components,and the main targets were PTGS2,PTGS1,HSP90 AB1,ER,PDE3 A and so on.Those targets were related with 45 diseases including Cancer,Cardiovascular disease,Nervous system disease,Immune system diseaseand so on.The main active components acted on the targets affecting the corresponding pathways in the treatment of diseases,the pathways influenced by the main components of Panax notoginseng containedPathways in cancer,Signal Transduction,Innate Immune System,and so on,indicating that Panax notoginseng has multiple components,targets,pathways providing synergistic effects in the treatment of diseases.Conclusion The study revealed the main active components of Pueraria lobata and related multidimensional action pharmacology mechanism by pharmacology network,providing the scientific basis for the development and application of Panax notoginseng.
引文
[1]中国药典[S].一部.2015.
[2]夏鹏国,张顺仓,梁宗锁,等.三七化学成分的研究历程和概况[J].中草药,2014,45(17):2564-2568.
[3]陈国铭,汤顺莉,许华,等.基于系统药理学的茵陈作用机制研究[J].中国药房,2018,29(10):1313.
[4]裴梦婕.系统药理学研究补气和补血中药作用机理:预测新药及新靶点[D].西安:西北大学,2014.
[5]李昕,潘俊娴,陈士国,等.葛根化学成分及药理作用研究进展[J].中国食品学报,2017,17(9):189-195.
[6]Russo M,Spagnuolo C,Tedesco I,et al.The flavonoid quercetin in disease prevention and therapy:Facts and fancies[J].Biochem Pharmacol,2012,83(1):6-15.
[7]Bischoff S C.Quercetin:Potentials in the prevention and therapy of disease[J].Curr Opin Clin Nutr Metab Care,2008,11(6):733-740.
[8]李庆勇,姜春菲,张黎,等.β-谷甾醇、豆甾醇有道人肝癌细胞SMMC-7721凋亡[J].时珍国医国药,2012,23(5):1175.
[9]许欣,姚东颖.结直肠癌中Girdin和Akt1蛋白的表达及临床意义[J].河北医药,2016,38(15):2259.
[10]赵清爽,王守森.TP53在髓母细胞瘤分子分型中的临床意义与相关研究进展[J].临床神经外科杂志,2017,14(4):315.
[11]徐明义,郑艳秋,孙娟,等.头颈部鳞癌中TP53基因的调控网络分析[J].局解手术学杂志,2016,25(12):863-867.
[2]夏鹏国,张顺仓,梁宗锁,等.三七化学成分的研究历程和概况[J].中草药,2014,45(17):2564-2568.
[3]陈国铭,汤顺莉,许华,等.基于系统药理学的茵陈作用机制研究[J].中国药房,2018,29(10):1313.
[4]裴梦婕.系统药理学研究补气和补血中药作用机理:预测新药及新靶点[D].西安:西北大学,2014.
[5]李昕,潘俊娴,陈士国,等.葛根化学成分及药理作用研究进展[J].中国食品学报,2017,17(9):189-195.
[6]Russo M,Spagnuolo C,Tedesco I,et al.The flavonoid quercetin in disease prevention and therapy:Facts and fancies[J].Biochem Pharmacol,2012,83(1):6-15.
[7]Bischoff S C.Quercetin:Potentials in the prevention and therapy of disease[J].Curr Opin Clin Nutr Metab Care,2008,11(6):733-740.
[8]李庆勇,姜春菲,张黎,等.β-谷甾醇、豆甾醇有道人肝癌细胞SMMC-7721凋亡[J].时珍国医国药,2012,23(5):1175.
[9]许欣,姚东颖.结直肠癌中Girdin和Akt1蛋白的表达及临床意义[J].河北医药,2016,38(15):2259.
[10]赵清爽,王守森.TP53在髓母细胞瘤分子分型中的临床意义与相关研究进展[J].临床神经外科杂志,2017,14(4):315.
[11]徐明义,郑艳秋,孙娟,等.头颈部鳞癌中TP53基因的调控网络分析[J].局解手术学杂志,2016,25(12):863-867.