基于网络药理学结合分子对接技术分析血平片治疗月经不调的作用机制

Analysis on mechanism of Xueping Tablets in treatment of irregular menstruation based on network pharmacology and molecular docking technique

目的运用网络药理学和分子对接技术探讨血平片治疗月经不调的作用机制。方法通过中药系统药理学数据库与分析平台(TCMSP)检索血平片有效成分的活性靶点,GeneCard和Disgenet数据库检索与“irregular menstruation”相关的疾病靶点,筛选出交集靶点并输入String数据库构建蛋白互作网络,利用Cypscape数据库分析并筛选出核心靶点,构建疾病–通路–靶点–化学成分网络。使用David数据库对交集靶点进行基因本体(GO)和京东基因与基因组百科全书(KEGG)通路富集分析。结果通过网络拓扑关系图筛选出了柚皮素、大黄酚、山柰酚、甲基异茜草素、大黄素和大黄素甲醚6个主要成分与丝苏氨酸特异性蛋白激酶(Akt1)、肿瘤坏死因子(TNF)、原癌基因酪氨酸蛋白激酶(SRC)、雌激素受体1(ESR1)、表皮生长因子受体(EGFR)和过氧化物酶体增殖物激活受体γ(PPARG)6个核心靶点进行分子对接验证。结果显示,血平片活性成分大黄素、甲基异茜草素、山柰酚等与Akt1、TNF、SRC、ESR1、EGFR、PPARG均有较好的结合活性。结论血平片可通过多成分作用多靶点治疗月经不调。

Objective To investigate the mechanism of Xueping Tablets in treatment of irregular menstruation based on network pharmacology and molecular docking technique.Methods TCMSP database was used to search the active targets of the active ingredients of Xueping Tablets,GeneCard and Disgenet databases were used to search the disease targets related to“irregular menstruation”,and the intersecting targets were screened and inputted into the String database to construct a protein-pathway-target interactions network.The disease-pathway-target-chemical composition drug network was constructed by analyzing and screening the core targets using Cypscape database.The core targets were analyzed and screened by Cypscape database,and the disease-pathwaytarget-chemical component drug network was constructed.The intersecting targets were analyzed by David database for gene ontology(GO)function and KEGG pathway enrichment.Results Naringenin,rhubarb phenol,kaempferol,rubiadin,rhodopsin and rhodopsin methyl ether were screened by network topology mapping for their association with serine threonine specific protein kinase(AKT1),tumor necrosis factor(TNF),proto-oncogene tyrosine protein kinase(SRC),estrogen receptor 1(ESR1),epidermal growth factor receptor(EGFR),peroxisome.The molecular docking validation of the first six core targets of peroxisome proliferator-activated receptorγ(PPARG)showed that rhodopsin,rubiadin,kaempferol and other active ingredients of blood leveling tablets had better binding activities with AKT1,TNF,SRC,ESR1,EGFR and PPARG.Conclusion Xueping Tablets can treat irregular menstruation through multi-component action and multi-target.