决明子抗氧化作用机制的网络药理学分析

Network pharmacological analysis of anti-oxidant mechanism of Cassia semen

中药决明子抗氧化作用显著但作用机制仍不清楚,本文旨在运用网络药理学研究方法,阐释决明子的抗氧化作用机制。通过文献和中药系统数据库TCMSP获取决明子的所有化学成分,再根据口服生物利用度(oral bioavailability,OB)和类药性(drug-likeness,DL)筛选出其活性成分及其对应靶点。通过GeneCards数据库查找并预测决明子抗氧化作用靶点,将靶点导入STRING数据库构建靶点间蛋白互作关系,并使用Cytoscape软件进行可视化处理。通过DAVID数据库对靶点进行GO功能富集和KEGG通路富集分析。利用AutoDock软件对预测结果进行分子对接验证。最终共筛选出决明子抗氧化作用活性成分11个,抗氧化作用靶点34个,这些靶点主要富集于氧化还原过程(oxidation-reduction process)、正调控活性氧代谢过程(positive regulation of reactive oxygen species metabolic process)等51个生物过程,参与了乙型肝炎相关通路(hepatitis B)、p53信号通路(p53 signaling pathway)、肿瘤坏死因子信号通路(TNF signaling pathway)、非酒精性脂肪肝(non-alcoholic fatty liver disease)和癌症信号通路(pathway in cancer)等154条信号通路。分子对接证实芦荟大黄素、决明内酯等成分可与对应靶点结合,进一步验证了网络药理学预测的可靠性。本研究发现决明子可通过大黄酸、芦荟大黄素、豆甾醇、决明内酯等11种成分作用于TP53、MYC、CASP3、ESR1、JUN等34个靶点发挥抗氧化作用,反映了决明子经多靶点、多途径发挥抗氧化作用的特点,为深入研究决明子抗氧化作用机制提供了参考。

Cassia semen is good at anti-oxidant,however the mechanism is unknown.The aim of the study was to investigate the anti-oxidative mechanisms of Cassia semen by the network pharmacological method.According to literature mining and TCMSP database of the Chinese medicine system,all the chemical components and the targets of Cassia semen were obtained.Then,the corresponding targets and the active components were selected according to oral bioavailability(OB)and drug-likeness(DL).GeneCards database was used to identify and predict the anti-oxidative targets of Cassia semen.STRING database and Cytoscape software were used to construct protein-protein interaction network.GO and KEGG enrichment analysis was preformed through DAVID database.The predicted targets were finally confirmed by molecular docking with AutoDock software.It was found that 11 ingredients and 34 targets were involved in 51 biological process GO terms(including oxidation-reduction process,positive regulation of reactive oxygen species metabolic process)and 154 KEGG pathways(including hepatitis B,p53 signaling pathway,TNF signaling pathway,non-alcoholic fatty liver disease and pathway in cancer).The predicted targets of Cassia semen were confirmed by molecular docking,which indicated the reliability of the network pharmacology approach.In conclusion,Cassia semen,including rhein,aloe-emodin,stigmasterol,toralactone etc.Eleven active ingredients,played its anti-oxidative role by interacting with 34 targets including TP53,MYC,CASP3,ESR1,JUN etc,which suggested the characteristic of multi-targets and multi-pathways of Cassia semen and provided a reference for further investigation.