基于网络药理学探讨朱日亨滴丸治疗冠心病的分子机制
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摘要
目的基于网络药理学方法探讨蒙药方剂朱日亨滴丸治疗冠心病的分子作用机制和潜在活性成分。方法通过文献挖掘、数据库检索收集整理朱日亨滴丸各味药材的化学成分,并进行口服生物利用度(OB)和类药性(DL)分析筛选;利用PharmMapper在线工具预测朱日亨滴丸所含化合物的潜在靶点;通过MAS 3.0在线工具对朱日亨滴丸的化合物靶点进行KEGG通路富集;应用Cytoscape软件建立朱日亨滴丸的"化合物-靶点-药物网络模型"和"化合物-靶点-通路-疾病网络模型",并对网络模型进行分析。结果网络拓朴学分析结果显示酪氨酸蛋白磷酸酯酶非受体1型(PTPN1)、视黄酸受体RXR-α(RXRA)、3-磷酸肌醇依赖蛋白酶1(PDPK1)、促分裂原活化蛋白激酶14(MAPK14)等是朱日亨滴丸的主要靶点;介数及网络度排序在前面的20个化合物有16个化合物为基础方中广枣、肉豆蔻、檀香的化合物,三味药材各占1/3。广枣、肉豆蔻、檀香的平均介数值均高于其他药材化合物平均介数,其中,广枣的平均介数最高。通路富集结果表明,朱日亨滴丸对与冠心病发病机制相关的生物学途径主要有:黏着斑、胰岛素信号通路、VEGF信号通路、Fc&RI信号通路、T细胞受体信号通路、ErbB信号通路、 PPAR信号通路、MAPK信号通路等;朱日亨滴丸与治疗冠心病的药物多存在共靶。结论朱日亨滴丸对冠心病、心肌缺血治疗作用是多成分、多靶点、多途径的协同作用,广枣、肉豆蔻、檀香是方中最重要的三味药材。
Objective To study the molecular mechanism and active component of Mongolian Prescription ZhuRiheng drop pill in treating coronary heart disease(CHD)based on network pharmacology. Methods Through the literature mining and Chinese medicine database retrieval, the compound of ZhuRiheng drop pill was collected. The oral bioavailability(OB)and drug similarity(DL) of compounds were analyzed and screened by TCMSP. Using the PharmMapper target prediction platform, the potential targets for the compounds were predicted. KEGG pathway enrichment was performed on the compound target of ZhuRiheng drop pill with MAS 3.0. The "compound-target-drug" network model and "compound-target-pathway-disease" network model were established with Cytoscape software, and the network model was analyzed. Results The results of network topology analysis showed that PTPN1, RXRA, PDPK1 and MAPK14 were the main targets of ZhuRiheng drop pill. Sixteen compounds in the preceding 20 compounds ordered by Betweenness and Degree derived from the basic prescription were composed of Fructus choerospondiatis, Nutmeg, Sandalwood, and each of these was 1/3. The average Betweenness values of Fructus choerospondiatis, Nutmeg, Sandalwood were higher than those of other medicinal compounds, among which the average Betweenness of fructus choerospondiatis was the highest. The pathway enrichment results indicated that the biological pathways of ZhuRiheng drop pill associated with the pathogenesis of CHD mainly included focal adhesion, insulin signaling pathway, ErbB signaling pathway, VEGF signaling pathway, Fc epsilon RI signaling pathway, T cell receptor signaling pathway, PPAR signaling pathway, MAPK signaling pathway,etc.ZhuRiheng drop pill and CHD drug have many common targets. Conclusion The mechanism of ZhuRiheng drop pill treating CHD is a synergistic effect by multi-component, multi-target, multi-channel. Fructus choerospondiatis, Nutmeg, Sandalwood are the most important materials.
Objective To study the molecular mechanism and active component of Mongolian Prescription ZhuRiheng drop pill in treating coronary heart disease(CHD)based on network pharmacology. Methods Through the literature mining and Chinese medicine database retrieval, the compound of ZhuRiheng drop pill was collected. The oral bioavailability(OB)and drug similarity(DL) of compounds were analyzed and screened by TCMSP. Using the PharmMapper target prediction platform, the potential targets for the compounds were predicted. KEGG pathway enrichment was performed on the compound target of ZhuRiheng drop pill with MAS 3.0. The "compound-target-drug" network model and "compound-target-pathway-disease" network model were established with Cytoscape software, and the network model was analyzed. Results The results of network topology analysis showed that PTPN1, RXRA, PDPK1 and MAPK14 were the main targets of ZhuRiheng drop pill. Sixteen compounds in the preceding 20 compounds ordered by Betweenness and Degree derived from the basic prescription were composed of Fructus choerospondiatis, Nutmeg, Sandalwood, and each of these was 1/3. The average Betweenness values of Fructus choerospondiatis, Nutmeg, Sandalwood were higher than those of other medicinal compounds, among which the average Betweenness of fructus choerospondiatis was the highest. The pathway enrichment results indicated that the biological pathways of ZhuRiheng drop pill associated with the pathogenesis of CHD mainly included focal adhesion, insulin signaling pathway, ErbB signaling pathway, VEGF signaling pathway, Fc epsilon RI signaling pathway, T cell receptor signaling pathway, PPAR signaling pathway, MAPK signaling pathway,etc.ZhuRiheng drop pill and CHD drug have many common targets. Conclusion The mechanism of ZhuRiheng drop pill treating CHD is a synergistic effect by multi-component, multi-target, multi-channel. Fructus choerospondiatis, Nutmeg, Sandalwood are the most important materials.
引文
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[3] NEJAD K H,GHARIB-NASERI M K,SARKAKI A,et al.Effects of ellagic acid pretreatment on renal functions disturbances induced by global cerebral ischemic-reperfusion in rat[J].Iran J Basic Med Sci,2017,20(1):75-82.
[4] CHEN C M,WU C T,YANG T H,et al.Green tea catechin prevents hypoxia/reperfusion-evoked oxidative stress-regulated autophagy-activated apoptosis and cell death in microglial cells[J].J Agric Food Chem,2016,64(20):4078-4085.
[5] ABOURASHED E A,EI-ALFY A T.Chemical diversity and pharmacological significance of the secondary metabolites of nutmeg(Myristica fragrans Houtt.)[J].Phytochem Rev,2016,15(6):1035-1056
[6] 方爱娟,徐凯节.肉豆蔻的化学成分及生物活性研究进展[J].中国药业,2013,22(15):113-115
[7] 吴纯伟,路丽,梁生旺,等.药物靶标预测技术在中药网络药理学中的应用[J].中国中药杂志,2016,41(3):375-382.
[8] YOON J,BLUMER A,LEE K.An algorithm for modularity analysis of directed and weighted biological networks based on edge-betweenness centrality[J].Bioinformatics,2006,22(24):3106-3108.
[9] YANG M,CHEN J L,XU L W,et al.Navigating traditional chinese medicine network pharmacology and computational tools[J].Evid Based Compl Altern Med,2013:731969.