基于网络药理学和分子对接探究三棱-莪术抗乳腺癌的作用机制

运用网络药理学和分子对接探究三棱-莪术药对抗乳腺癌的有效活性成分及分子机制。通过中药系统药理学数据库与分析平台检索并筛选出三棱、莪术的有效活性成分和对应作用靶点,运用OMIM数据库、GeneCards数据库检索乳腺癌的疾病靶点。运用Cytoscape 3.7.2软件绘制药物-成分-疾病-靶点网络图。利用STRING数据库构建蛋白质-蛋白质相互作用(protein- protein interaction,PPI)网络,使用Cytoscape中MCODE插件进行分析并筛选出前10个核心靶点。借助DAVID数据库对作用靶点进行基因本体及京都基因与基因组百科全书(Kyoto encyclopedia of genes and genomes, KEGG)通路富集分析,并绘制成分-靶点-通路网络图。最后通过AutoDock Vina等软件进行分子对接,验证核心成分与核心靶点的相互作用。结果表明,通过筛选得出7种活性成分、73个作用靶点,三棱-莪术与乳腺癌共同靶点43个。核心成分为常春藤皂苷元、β-谷甾醇、芒柄花黄素、豆甾醇、反式软骨酸,PPI网络显示其核心靶点为JUN、CASP3、PTGS2、ESR1、MPK14、PPARG、SIRT1、NOS3、TGFB1、NOS2。KEGG富集分析得到72条通路,根据P值筛选出与乳腺癌相关的前20条,主要涉及PI3K-Akt通路、VEGF通路、p53通路、MAPK通路等。分子对接显示活性成分与核心靶点之间有较好的结合力。研究表明三棱-莪术药对抗乳腺癌具有多成分、多靶点、多通路的特点,为该药对在临床中的应用提供了理论依据。

Mechanism of the anti-breast cancer effect of Sparganii Rhizoma-Curcumae Rhizoma herbal pair based on network pharmacology and molecular docking

To explore the active ingredients and mechanisms of Sparganii Rhizoma-Curcumae Rhizoma herbal pair in breast cancer using network pharmacology and molecular docking. The effective active ingredients and corresponding targets of Sparganii Rhizoma and Curcumae Rhizoma were searched and screened using the traditional Chinese medicine systems pharmacology database and analysis platform,and the disease targets of breast cancer were searched using the OMIM and GeneCards databases. Cytoscape 3.7.2 software was used to construct a visual network diagram of drug-ingredient-disease-targets. A protein-protein interaction network (PPI) was constructed using STRING database platform, and the MCODE plug-in in Cytoscape was used for analysis to screen the top 10 core targets. Gene ontology and Kyoto encyclopedia of genes and genomes(KEGG) enrichment pathway analyses of the targets of action were performed using DAVID database, and the network diagram of ingredient-target-pathway was plotted. Finally, molecular docking was performed using autodock Vina and other software to verify the interaction between the core ingredients and the core targets. Seven active components and 73 action targets were obtained through screening. There were 43 common targets of Sparganii Rhizoma and Curcumae Rhizoma and breast cancer. The active components were hederagenin, beta-sitosterol, formononetin, stigmasterol, and trans-gondoic acid. The PPI network showed that the key targets were JUN, CASP3, PTGS2, ESR1, MPK14, PPARG, SIRT1, NOS3, TGFB1 and NOS2. The KEGG pathway enrichment analysis revealed 72 items. According to the P values, the first 20 items related to breast cancer were eliminated via screened, including the PI3K-Akt signaling pathway, VEGF signaling pathway, p53 signaling pathway, and MAPK signaling pathway. The molecular docking results showed that the active ingredients had strong binding ability in docking with the core targets. Therefore, our results suggest that Sparganii Rhizoma-Curcumae Rhizoma herbal pair has characteristics of a multi-ingredient, multi-target, and multi-pathway on breast cancer, which provides a theoretical basis for its clinical application in the future.