基于网络药理学黄芩-黄连药对治疗2型糖尿病作用机制探讨
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摘要
目的探讨黄芩-黄连药对治疗2型糖尿病(T2DM)的作用机制。方法借助中药系统药理学分析平台(TCMSP)检索黄芩、黄连的化学成分和作用靶点,通过OMIM、TTD、Drugbank、Digsee等多个数据库查询与T2DM相关的基因。通过Uni Prot数据库查询靶点对应的基因,进而运用Cytoscape3.2.1构建化合物-靶点(基因)网络、蛋白相互作用(PPI)网络筛选出核心靶点,最后通过DAVID进行基因本体(GO)功能富集分析和基于京都基因与基因组百科全书(KEGG)通路富集分析,研究其作用机制。结果化合物-靶点网络包含42个化合物和相应靶点213个,关键靶点涉及PTGS2、PTGS1、HSP90AA1、HSP90AB1、NOS2等。PPI核心网络包含15个蛋白,关键蛋白涉及TNF、IL6、INSR等。GO功能富集分析得到GO条目108个(P<0.05),其中生物过程(BP)条目87个,分子功能(CC)条目9个,细胞组成(MF)条目12个。KEGG通路富集筛选得到24条信号通路(P<0.05),涉及胰岛素抵抗通路、T2DM通路、胰岛素信号传递通路等。结论黄芩-黄连中的活性成分主要通过DPP4、PPARG、IL6、PPARD、TNF等靶点调节炎症细胞因子、作用于胰岛素受体协同治疗T2DM。
Objective To investigate the mechanism of type 2 diabetes mellitus(T2 DM) treatment by drug pair containing Scutellariae Radix and Coptidis Rhizoma. Methods The chemical composition and targets of Scutellariae Radix and Coptidis Rhizoma were searched by the analysis of traditional Chinese medicine system pharmacology platform(TCMSP), and T2 DM related genes were searched by OMIM, TDD, Drugbank, and Digsee databases. UniProt database was used to query the target-related genes. Cytoscape3.2.1 was used to construct compound-targets(genes) networks and protein-protein interaction(PPI) network to screen out the key targets. Finally, the mechanism of its action was studied by DAVID analyzing enrichment of gene ontology(GO) function and pathway enrichment analysis based on Kyoto Encyclopedia of Genes and Genomes(KEGG). Results The compound-target network contained 42 compounds and 213 corresponding targets, and the key targets involved PTGS2, PTGS1, HSP90 AA1, HSP90 AB1,NOS2, etc. The PPI core network contained 15 protein, and key protein involved in TNF, IL-6, INSR, etc. The functional enrichment analysis of GO obtained 108 GO items(P < 0.05), of which there were 87 biological processes(BP) items, 9 molecular function(CC)items, and 12 related items of cell composition(MF). There were 24 signal pathways(P < 0.05) in the KEGG pathway enrichment screening, involving insulin resistance, T2 DM and insulin signaling pathway and so on. Conclusion The active components of Scutellariae Radix and Coptidis Rhizoma regulate inflammatory cytokines and act on insulin receptor in the treatment of T2 DM mainly through DPP4, PPARG, IL6, PPARD, TNF, and other targets.
Objective To investigate the mechanism of type 2 diabetes mellitus(T2 DM) treatment by drug pair containing Scutellariae Radix and Coptidis Rhizoma. Methods The chemical composition and targets of Scutellariae Radix and Coptidis Rhizoma were searched by the analysis of traditional Chinese medicine system pharmacology platform(TCMSP), and T2 DM related genes were searched by OMIM, TDD, Drugbank, and Digsee databases. UniProt database was used to query the target-related genes. Cytoscape3.2.1 was used to construct compound-targets(genes) networks and protein-protein interaction(PPI) network to screen out the key targets. Finally, the mechanism of its action was studied by DAVID analyzing enrichment of gene ontology(GO) function and pathway enrichment analysis based on Kyoto Encyclopedia of Genes and Genomes(KEGG). Results The compound-target network contained 42 compounds and 213 corresponding targets, and the key targets involved PTGS2, PTGS1, HSP90 AA1, HSP90 AB1,NOS2, etc. The PPI core network contained 15 protein, and key protein involved in TNF, IL-6, INSR, etc. The functional enrichment analysis of GO obtained 108 GO items(P < 0.05), of which there were 87 biological processes(BP) items, 9 molecular function(CC)items, and 12 related items of cell composition(MF). There were 24 signal pathways(P < 0.05) in the KEGG pathway enrichment screening, involving insulin resistance, T2 DM and insulin signaling pathway and so on. Conclusion The active components of Scutellariae Radix and Coptidis Rhizoma regulate inflammatory cytokines and act on insulin receptor in the treatment of T2 DM mainly through DPP4, PPARG, IL6, PPARD, TNF, and other targets.
引文
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[19]胡承,贾伟平,方启晨,等.PPARD-87T→C基因多态性与代谢综合征的关联研究[J].中华内分泌代谢杂志,2005,21(4):380-383.
[20]陈瑶.黄精对2型糖尿病大鼠糖脂代谢及TNF-α水平影响的研究[D].北京:北京中医药大学,2018.
[21]郑勇凤,王佳婧,傅超美,等.黄芩的化学成分与药理作用研究进展[J].中成药,2016,38(1):141-147.
[22]李骏豪,沈涛.浅谈黄连、吴茱萸在冠心病治疗中的运用[J].中国中医药现代远程教育,2010,8(1):17.
[23]王建礼,杨作成,王聪,等.槲皮素对糖尿病大鼠的降糖作用及机制研究[J].济宁医学院学报,2018,41(2):135-138.
[24]田硕,洪涛,张多,等.黄芩素的药理作用及分子机制的最新研究进展[J].黑龙江医药,2015,28(6):1195-1199.
[2]IDF.TheIDFDiabetesAtlas7thedition[EB/OL].(2015-11-14)[2016-04-01].http://www.diabetesatlas.org.
[3]Chan J C,Zhang Y,Ning G.Diabetes in China:A societal solution for a personal challenge[J].Lancet Diabetes Endocrinol,2014,2(12):969-979.
[4]宗阳,孙明明,乐音子,等.基于网络药理学探讨白术-枳实药对治疗慢传输型便秘的作用机制[J].中国药房,2018,29(13):1798-1802.
[5]冯瑾.黄芩-黄连药对药代动力学及相互作用研究[D].上海:第二军医大学,2010.
[6]徐君.黄芩-黄连药对与肠道菌群的相互作用研究[D].南京:南京中医药大学,2014.
[7]冯燕燕,谢媛媛,汪艳平,等.基于“药物-靶点-通路”网络的血必净注射液治疗脓毒症分子调控机制[J].药学学报,2017,52(4):2666-2670.
[8]许文倩,秦雪梅,刘月涛.基于网络药理学的黄芪建中汤治疗慢性萎缩性胃炎作用机制研究[J].中草药,2018,49(15):3550-3561.
[9]白隆博,马逍遥,常念伟,等.基于整合网络药理学和化学物质组学的灯台叶片的抗炎作用机制研究[J].中草药,2018,49(16):3861-3867.
[10]高耀,吴丹,田俊生,等.逍遥散和开心散“同病异治”抑郁症的网络药理学作用机制研究[J].中草药,2018,49(15):3483-3492.
[11]Ru J,Li P,Wang J,et al.TCMSP:A database of systems pharmacology for drug discovery from herbal medicines[J].J Cheminform,2014,6(1):13-18.
[12]Ahmed S S,Ramakrishnan V.Systems biological approach of molecular descriptors connectivity:Optimal descriptors for oral bioavailability prediction[J].PLoSOne,2012,7(7):e40654.
[13]Ursu O,Rayan A,Goldblum A,et al.Understanding drug-likeness[J].Wires Comput Mol Sci,2011,1(5):760-781.
[14]刘鑫馗,吴嘉瑞,张丹,等.基于网络药理学的参附汤作用机制分析[J].中国实验方剂学杂志,2017,23(16):211-218.
[15]李晓燕,董姝,魏滨,等.六味地黄汤中药成分-靶标-疾病网络分析及效应机制预测[J].中国实验方剂学杂志,2017,23(5):189-195.
[16]刘瑛.DPP4抑制剂治疗2型糖尿病的系统评价[D].昆明:昆明医科大学,2016.
[17]唐新,林婴,黄文芳,等.PPARG基因单核苷酸多态性与2型糖尿病血脂异常的相关性研究[J].检验医学,2009,24(3):190-193.
[18]张龙江,林汉华,王宏伟.白介素6与肥胖及2型糖尿病[J].临床儿科杂志,2005,23(5):332-334.
[19]胡承,贾伟平,方启晨,等.PPARD-87T→C基因多态性与代谢综合征的关联研究[J].中华内分泌代谢杂志,2005,21(4):380-383.
[20]陈瑶.黄精对2型糖尿病大鼠糖脂代谢及TNF-α水平影响的研究[D].北京:北京中医药大学,2018.
[21]郑勇凤,王佳婧,傅超美,等.黄芩的化学成分与药理作用研究进展[J].中成药,2016,38(1):141-147.
[22]李骏豪,沈涛.浅谈黄连、吴茱萸在冠心病治疗中的运用[J].中国中医药现代远程教育,2010,8(1):17.
[23]王建礼,杨作成,王聪,等.槲皮素对糖尿病大鼠的降糖作用及机制研究[J].济宁医学院学报,2018,41(2):135-138.
[24]田硕,洪涛,张多,等.黄芩素的药理作用及分子机制的最新研究进展[J].黑龙江医药,2015,28(6):1195-1199.