基于网络药理学与分子对接技术探讨生血宁治疗贫血的机制

Potential clinical mechanism of Shengxuening on network pharmacology in the treatment of anemia

目的:利用网络药理学和分子对接技术,探讨生血宁主要成分蚕沙治疗贫血的作用机制。方法:借助中药系统药理学数据库与分析平台(Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform,TCMSP)筛查生血宁有效成分,与GeneCards网站收集的靶点取交集后,筛选出生血宁治疗贫血的重合靶点,绘制中药-活性成分-靶点网络图。利用STRING构建药物治疗贫血的蛋白-蛋白相互作用网络(PPI),同时对重合靶点进行基因本体的分子功能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,最后通过分子对接探究核心成分与核心靶点的相互作用。结果:基因本体(gene ontology,GO)分析和KEGG通路富集结果显示生血宁主要通过调节AMP激活的蛋白质激酶(AMP-activated protein kinase,AMPK)和丝裂原活化蛋白激酶(mitogen-activated protein kinase,MAPK)等通路发挥治疗贫血作用。分子对接结果显示生血宁中活性成分可与蛋白激酶B1(又称AKT1)发生相互作用,其中叶酸和AKT1氨基酸残基ARG 379、ARG 369、RG 99和ASP 540等结合。结论:生血宁的作用机制涉及多靶点多通路,为阐明生血宁治疗贫血的药效学提供了理论依据。

OBJECTIVE To explore the mechanism of Cansha as a major constituent in Shengxuening for treating anemia based upon network pharmacology and molecular docking.METHODS The active ingredients of Shengxuening were screened with an aid of Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP).After intersecting with the targets from the GeneCards website,the overlapping targets of Shengxuening for treating anemia were identified.A network diagram of traditional Chinese medicine-active ingredient-target points was drawn.STRING was employed for constructing a protein-protein interaction network(PPI)for drug dosing of anemia.And gene ontology molecular functions and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis were performed for overlapping targets.Finally the interaction between core components and core targets was explored through molecular docking.RESULTS GO analysis in combination with KEGG pathway enrichment indicated that Shengxuening played an important role in the treatment of anemia through regulating the pathways of AMP-activated protein kinase(AMPK)and mitogen-activated protein kinase(MAPK).Through molecular docking approach,it was predicted that interactions existed between the active components of Shengxuening and Akt1.And folic acid and Akt1 could closely bind through such amino acid residues as Arg 379,Arg 369,Rg 99 and Asp 540.CONCLUSION The proposed mechanism of Shengxuening involves multiple targets and pathways.It provides theoretical rationales for further elucidating the its pharmacodynamics in the treatment of anemia.