Utilising network pharmacology to explore the underlying mechanism of Wumei Pill in treating pancreatic neoplasms
Utilising network pharmacology to explore the underlying mechanism of Wumei Pill in treating pancreatic neoplasms
复制标题
利用网络药理学探讨乌梅丸治疗胰腺肿瘤的潜在机制
DOI：
10.1186/s12906-019-2580-y
复制
发表时间：
2019-07-04
影响因子：
--
通讯作者：
Huang, Jinchang
中科院分区：
文献类型：
--
作者：
Wan, Yuxiang;Xu, Lin;Huang, Jinchang
乌梅丸是我国著名的中药方剂，在临床上用于治疗消化系统疾病已有数百年的历史。我们发现WMP的适应症与胰腺肿瘤的典型症状之间存在相关性。然而，WMP的药理学机制仍然是未知的。MethodsIn目前的工作中，我们使用了网络药理学方法来预测其治疗胰腺肿瘤的潜在复杂机制。首先，基于TCMSP数据库、TCM数据库@Taiwan和TCMID数据库，获得了WMP的相关化合物，并通过目标钓鱼法收集了这些化合物的潜在靶标。利用CTD、TTD、PharmGKB建立胰腺肿瘤靶点数据库。根据WMP潜在靶点与胰腺肿瘤靶点的匹配结果，构建PPI网络，分析这些靶点之间的相互作用，并根据拓扑结构筛选枢纽靶点。利用大卫生物信息学资源对GO_BP和KEGG进行富集分析。大卫富集分析结果表明，WMP的58个细胞生物学过程（FDR < 0.01）和17条通路（FDR < 0.01）主要参与了与增殖、凋亡、炎症反应和血管生成相关的复杂治疗作用。此外，WMP的17个中枢节点（PTGS 2、BCL 2、TP 53、IL 6、MAPK 1、EGFR、EGF、CASP 3、JUN、MAPK 8、MMP 9、VEGFA、TNF、MYC、AKT 1、FOS和TGFB 1）被认为是治疗胰腺肿瘤的潜在靶点，揭示了WMP治疗胰腺肿瘤的可能机制。本研究提出了一种从网络药理学水平阐明中药作用机制的策略。
BackgroundWumei Pill (WMP), a famous herbal formula, has been widely used to treat digestive system diseases in clinical practice in China for centuries. We have found a correlation between the indications of WMP and the typical symptoms of pancreatic neoplasms. However, the pharmacological mechanisms of WMP still remain unknown.MethodsIn the present work, we used a network pharmacological method to predict its underlying complex mechanism of treating pancreatic neoplasms. Firstly, we obtained relative compounds of WMP based on TCMSP database, TCM database@Taiwan and TCMID database and collected potential targets of these compounds by target fishing. Then we built the pancreatic neoplasms target database by CTD, TTD, PharmGKB. Based on the matching results between WMP potential targets and pancreatic neoplasms targets, we built a PPI network to analyze the interactions among these targets and screen the hub targets by topology. Furthermore, DAVID bioinformatics resources were utilized for the enrichment analysis on GO_BP and KEGG.ResultsA total of 80 active ingredients and 77 targets of WMP were picked out. The results of DAVID enrichment analysis indicated that 58 cellular biological processes (FDR < 0.01) and 17 pathways (FDR < 0.01) of WMP mostly participated in the complex treating effects associated with proliferation, apoptosis, inflammatory response and angiogenesis. Moreover, 17 hub nodes of WMP (PTGS2, BCL2, TP53, IL6, MAPK1, EGFR, EGF, CASP3, JUN, MAPK8, MMP9, VEGFA, TNF, MYC, AKT1, FOS and TGFB1) were recognized as potential targets of treatments, implying the underlying mechanisms of WMP acting on pancreatic neoplasms.ConclusionWMP could alleviate the symptoms of pancreatic neoplasms through the molecular mechanisms predicted by network pharmacology. This study proposes a strategy to elucidate the mechanisms of Traditional Chinese Medicine (TCM) at the level of network pharmacology.