基于网络药理学的猫爪草治疗结核病作用机制研究

Study on the mechanism of Ranunculi Ternati Radix in the treatment of tuberculosis based on network pharmacology

通过网络药理学方法探讨猫爪草治疗结核病的作用机制。运用中药系统药理学数据库与分析平台筛选猫爪草的活性成分和相关作用靶点;借助GeneCards数据库检索疾病靶点,活性成分靶点与疾病靶点作交集得到猫爪草作用于结核病的预测靶点;运用STRING数据库构建蛋白质-蛋白质相互作用网络图;将交集基因进行基因本体分析和京都基因与基因组百科全书(Kyoto encyclopedia of genes and genomes,KEGG)富集分析;最后应用AutoDock软件进行活性成分及潜在靶点之间的分子对接验证。筛选得到猫爪草的活性化合物12个,其有效活性成分主要作用于结核病的关键靶点有CASP3、CASP8、CASP9、BCL2和BAX。KEGG结果表明,猫爪草可能通过调节细胞凋亡信号通路从而对结核病进行干预。分子对接得到猫爪草的主要成分是豆甾-4,6,8、维太菊苷、豆甾醇、豆甾醇葡萄糖苷、谷甾醇乙酸酯和β-谷甾醇,对BAX、CASP3和CASP9作用明显。本研究从分子水平探讨了猫爪草治疗结核病的活性成分与潜在靶点,初步验证了其作用机制。

This study aimed to investigate the mechanism of Ranunculi Ternati Radix in the treatment of tuberculosis based on network pharmacology.The active ingredients and related targets of Ranunculi Ternati Radix were screened using the Traditional Chinese Medicine System Pharmacology database and analysis platform.With the help of the GeneCards database to search disease targets,the intersections of active ingredient targets and disease targets are used as the predicted targets of Ranunculi Ternati Radix for tuberculosis treatment.A protein-protein interaction network diagram was constructed using the STRING database,and gene ontoeogy and Kyoto encyclopedia of gene and genomes(KEGG)enrichment analyses were performed for the overlapping genes.Finally,molecular docking verification between active ingredients and potential targets was performed using the AutoDock software.In total,12 active compounds were selected from Ranunculi Ternati Radix.These active ingredients mainly act on the key targets of tuberculosis,including CASP3,CASP8,CASP9,BCL2,and BAX.KEGG results indicate that Ranunculi Ternati Radix may interfere with tuberculosis by regulating the apoptosis signaling pathway.The main components of Ranunculi Ternati Radix identified using molecular docking include stigmasta-4,6,8,vittadinoside,stigmasterol,stigmasterol glucoside,sitosterol acetate,and beta-sitosterol.These components were known to have obvious effects on BAX,CASP3,and CASP9.This study explored the active ingredients of Ranunculi Ternati Radix and corresponding potential targets when treating tuberculosis at the molecular level based on network pharmacology.Furthermore,the mechanism of action of Ranunculi Ternati Radix was verified.