基于网络药理学和主成分分析的痢泻灵片质量标志物研究

Quality markers of Lixieling Tablets based upon network pharmacology and principal component analysis

目的:预测评价痢泻灵片的质量标志物。方法:采用UPLC-QE-Orbitrap-MS技术,对痢泻灵片化学成分进行鉴定。通过SwissADME平台对化学成分进行ADME预测,结合化合物药理作用、对照品的可集性以及成分可测性综合分析得到先导成分;采用PharmMapper数据库预测先导成分作用靶点;利用GeneCards、OMIM、CTD和DisGenet数据库获取疾病靶点;构建韦恩图获取交集靶点作为痢泻灵片治疗的潜在作用靶点;利用Metascape平台将潜在作用靶点导入进行富集分析,得到痢泻灵片干预疾病的潜在作用通路;采用Cytoscape构建“成分-靶点-通路”网络图,判断核心靶点及主要活性成分。通过主成分分析对活性成分组合物和痢泻灵片的等效性在正常动物中进行评价。结果:网络药理学预测得出痢泻灵片的10个活性成分,包括穿心莲内酯、脱水穿心莲内酯、儿茶素、绿原酸、氧化槐果碱、氧化苦参碱、槐果碱、苦参碱、槐定碱和没食子酸。主成分分析结果显示活性成分组合物与痢泻灵片对正常动物具有相似的代谢调控作用。结论:通过网络药理学和主成分分析预测评价痢泻灵片的质量标志物,由10个活性成分组成的组合物在一定程度上与原制剂具有等效性。

OBJECTIVE To predict and evaluate the quality markers of Lixieling Tablets by network pharmacology and principal component analysis.METHODS UPLC-QE-Orbitrap-MS technology was utilized for identifying the chemical components of Lixieling Tablets.ADME prediction of chemical components was performed through SwissADME platform.The lead components were obtained by analyzing pharmacological effects of compounds,collectability of reference materials and the testability of components.PharmaMapper database was utilized for predicting the action targets of lead components.The databases of GeneCards,OMIM CTD and DisGenet were employed for screening disease targets.Venn diagram was constructed for harvesting intersection targets as potential therapeutic targets of Lixieling Tablets.Metascape platform was utilized for conducting enrichment analysis by introducing potential targets and obtaining the potential intervention pathway of Lixieling Tablets.Cytoscape software was utilized for constructing a network of"component-target-pathway"to identify core targets and major active ingredients.Principal component analysis was applied for evaluating the equivalence of the active ingredients and Lixieling Tablets in normal animals.RESULTS The network pharmacology predicted the ten active ingredients of Lixieling Tablets,including andrographolide,dehydroandrographolide,(+)-catechin,chlorogenic acid,oxysophocarpine,oxymatrine,sophocarpine,matrine,sophoridine and gallic acid.Principal component analysis revealed that active ingredients and Lixieling Tablets exhibited similar metabolic regulatory effects in normal animals.CONCLUSION Predicting and evaluating the quality markers of Lixieling Tablets are feasible through network pharmacology and principal component analysis.The complex of active ingredients is equivalent to original preparation to a certain extent.