目的:基于网络药理学探讨大黄-积雪草治疗特发性膜性肾病(Idiopathic membranous nephropathy,IMN)的作用机制.方法:采用中药系统药理数据库与分析平台(TCMSP)筛选大黄、积雪草活性成分,在Swiss Target Prediction数据库中获取对应靶点,通过GeneCards、OMIM及DisGeNET数据库获取IMN相关靶点,利用Venny作图工具筛选药对与疾病交集靶点.在STRING数据库中对交集靶点进行蛋白质-蛋白质相互作用网络构建.通过DAVID数据库对靶点进行基因本体论(GO)及京都基因与基因百科全书(KEGG)富集分析并构建"药物活性成分-靶点-通路图".在AutoDock及Pymol软件中对主要活性成分及交集靶点进行分子对接和可视化分析.结果:得到大黄-积雪草药对有效活性成分6个,有效活性成分与疾病交集靶点121个.由GO富集分析得到生物过程205个、细胞组分33个、分子功能61个.由KEGG富集分析得到73条通路.分子对接结果表明药物主要活性成分与主要交集靶点有较强的结合能力.结论:"大黄-积雪草"治疗IMN的主要活性成分为槲皮素、泽兰黄醇素、大黄酸,其主要作用于丝氨酸/苏氨酸蛋白激酶1(Akt Serine/Threonine Kinase 1,AKT1)、表皮生长因子受体(Epidermal Growth Factor Receptor,EGFR)、B 细胞淋巴瘤-2 基因(BCL2 Apoptosis Regulator,BCL2)等靶点,通过肿瘤坏死因子(Tumor Necrosis Factor,TNF)、晚期糖基化终末产物(Advanced Glycation End Product,AGE)-晚期糖基化终末产物受体(Receptor for Advanced Glycation End Product,RAGE)等信号通路调控炎症反应、细胞凋亡、自噬等降低炎症水平、抑制肾脏纤维化,保护IMN患者肾功能.
A study on the mechanism of Dahuang-Jixuecao couplet medicinals in the treatment of idiopathic membranous nephropathy based on network pharmacology
Objective:To explore the mechanism of Dahuang(Rheum officinale)-Jixuecao(Asiatic pennywort herb)couplet medicinals in the treatment of idiopathic membranous nephropathy(IMN)based on network pharmacology.Methods:The TCMSP was used to screen the active ingredients of Dahuang-Jixuecao couplet medicinals,and the corresponding targets were obtained from Swiss Target Prediction database.The targets related to IMN were obtained from GeneCards,OMIM and DisGeNET databases,and the Venny mapping tool was used to screen the intersection targets of couplet medicinals and diseases.The intersecting targets were used to construct protein-protein interaction(PPI)network using the STRING database.And the targets were analysed for GO and KEGG enrichment by the DAVID database,then'active ingredient-target-pathway graphs'were constructed.Molecular docking and visual analysis of the main active ingredients and intersection targets were carried out by AutoDock and Pymol software.Results:A total of 6 active components of Dahuang-Jixuecao couplet medicinals were obtained.There were one hundred and twenty-one targets of intersection of active components and diseases.A total of 205 biological processes,33 cellular components and 61 molecular functions were obtained by GO enrichment analysis.And 73 pathways were obtained by KEGG enrichment analysis.The molecular docking results indicated that the main active ingredients of the drug had strong binding ability to the main intersecting targets.Conclusion:The main active ingredients of Dahuang-Jixuecao couplet medicinals in the treatment of IMN are quercetin,eupatin and chrysophanic acid,which mainly act on the targets of AKT1,EGFR,BCL2 through the signalling pathways such as TNF and AGE-RAGE to regulate inflammatory reactions,apoptosis and autophagy,so as to reduce the level of inflammation,inhibit renal fibrosis,and protect the renal function of patients with IMN.
万方数据
维普
