基于生物信息学方法的坤泰胶囊分子网络及生物功能初步探析

Investigation for molecular network and biological functions of Kuntai Capsule baesd on bioinformatics analysis

目的基于和颜?坤泰胶囊(以下简称坤泰胶囊)各组分对应靶点信息集,运用生物信息学方法探析其发挥疗效的潜在分子网络及生物功能。方法将坤泰胶囊6味组方药材逐一在中药系统药理学研究数据库(TCMSP)、TCM-mesh中检索获得每一种药材所对应的化学成分,并与经液相色谱-电喷雾质谱联用技术(LC-ESI-MS/MS)检测得到的坤泰胶囊活性成分进行比对,剔除重复成分,获得坤泰胶囊含有的活性成分,再将这些成分逐一在数据库中检索获得其对应的靶点信息,形成化合物-靶点信息集。利用DAVID、KEGG、COSMIC等数据库,对化合物-靶点信息集进行功能富集分析、靶标的组织特异性表达分析,以及蛋白-蛋白相互关系网络分析。结果结合数据库与LC-ESI-MS/MS检测,共获得29个成分,获得对应的靶基因186个。这些靶基因显著富集在神经中枢、乳腺、卵巢等组织中。经DAVID的基因本体(gene ontology,GO)分析结果显示,这些靶标显著集中于细胞质、线粒体、细胞外基质等细胞器,主要发挥脂肪酶、激酶以及氧化还原酶等活性,参与代谢、能量通路、凋亡等生物过程。KEGG通路富集分析表明这些靶标显著参与PI3K-Akt、m TOR、胰岛素等信号通路。结论通过坤泰胶囊活性成分-靶标信息集的建立,利用各生物信息数据库与分析手段,从分子水平为坤泰胶囊的临床疗效提供佐证,也为进一步拓展其临床应用提供依据。

Objective To investigate the potential molecular functions and the involved signaling network of Heyan？Kuntai Capsules（HYKTc） based on the ingredient-gene targets clustering by means of bioinformatics analysis. Methods The ingredients in HYKTc were obtained by the combination of previous LC-ESI-MS/MS method and searched through Traditional Chinese Medicine System Pharmacology databases. Further the gene ontology（GO） and KEGG enrichment analysis were performed with Database for Annotation, Visualization, and Integrated Discovery（DAVID） tools. Results A total of 29 chemicals were obtained in which 21 chemicals were identified by LC-ESI-MS/MS method. Afterwards, 186 gene targets were acquired in the databases. The HYKTc-gene targets clustering were highly enriched in central nervous system, breast, and ovary. Subsequent GO analysis showed that these gene targets were significantly located in the cytosol, mitochondria and extracellular matrix, mainly functioning as lipase, kinase and oxidoreductase activity. Besides, KEGG results found that these targets were involved in the PI3 K-Akt, m TOR, and insulin signaling pathways. Conclusions Using TCM databases searching combined with bioinformatics methods, the potential explanations for the clinical efficiency of HYKTc were proveded for further clinical applications.