作者：杨云英，何莎莎，王岩，陈勇，王成涛

单位：中山大学附属第一医院 放射治疗科，广东 广州 510080

Authors:  YANG Yunying, HE Shasha, WANG Yan, CHEN Yong , WANG Chengtao

Unit:   Department of Radiation Oncology, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, Guangdong, China

摘要：

目的  基于网络药理学,探究仙鹤草对治疗结肠癌(Colon cancer)可能的作用机制。方法  利用中药系统药理学数据库与分析平台(TCMSP)数据库以及文献查阅,检索并收集仙鹤草成分的活性成分及其对应的靶标。通过Uniprot数据库和人类基因组注释数据库(Genecards),收集与结肠癌相关的靶标,并与药物成分所对应的靶标相比较,筛选出共同部分,获得仙鹤草与结肠癌重合的潜在靶基因。使用Cytoscape 3.6.0软件构建仙鹤草的"候选成分-作用靶标"网络。使omicshare平台将药物靶蛋白和疾病靶点相映射,并绘制Venn图。结合string数据库及Cytoscape软件中的Generate style from statistics工具,构建蛋白质相互作用网络。通过Systems Dock Web Site网络服务器与仙鹤草的活性成分进行分子对接。利用Database for Annotation, Visualization and Integration Discovery (DAVID)生物信息资源数据库,对仙鹤草的作用靶标进行京都基因与基因组百科全书(KEGG)通路富集分析和GO分类富集分析。结果  共从仙鹤草中筛选得到5个候选活性成分,包括ellagic acid(鞣花酸)、kaempferol(山奈酚)、(+)-catechin、luteolin(木犀草素)、quercetin(槲皮苷),和158个作用靶标,包括丝苏氨酸激酶(AKT1),肿瘤抑制基因p53 (TP53),白介素-6(IL-6),血管内皮生长因子(VEGF)、氨基端激酶(c-JUN)等,主要涉及低氧诱导因子1 (HIF-1),磷脂酰肌醇-3-激酶/蛋白激酶B(PI3K/Akt)等信号通路。结论  本研究基于网络药理学的方法初步预测了仙鹤草治疗结肠癌的可能的作用机制,为后续的深入研究提供了方向。

关键词： 仙鹤草; 结肠癌; 网络药理学; 靶标; 信号通路

Abstract：

Objective  To explore the possible mechanisms of Agrimonia pilosa in the treatment of Colon cancer based on the network pharmacology. Methods  The candidate active components and targets of Fructus Ligustri Lucidi and Ecliptae Herba were obtained through retrieval of the traditional Chinese medicine (TCM) systems pharmacology database (TCMSP) and literatures. Through Uniprot database and the human genome database (GeneCards), the overlapping genes of Agrimonia pilosa and Colon Cancer were collected. The “candidate active components-targets”network of Fructus Ligustri Lucidi and Ecliptae Herba was built with Cytoscape 3.6.0 software. Drug target proteins and disease targets were mapped, and Venn map was drawn by Omicshare database. Major targets interaction network was formed by using String database and “Generate style from statistics”tool in Cytoscape 3.6.0 software. Molecular docking with active components was carried out by Systems Dock Web Site. The Gene Ontology (GO) classification enrichment analysis and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis for the targets were carried out in DAVID database. Result  Totally 5 active components, including ellagic acid, kaempferol, (+)-catechin, luteolin, quercetin and 158 targets, including Protein kinase B (AKT1), Tumor suppressor gene p53 (TP53), Interleukin - 6 (IL-6), Vascular endothelial growth factor (VEGF)、N-terminal kinase (JUN) of Agrimonia pilosa were collected. Agrimonia pilosa exerts its effects on Colon Cancer mainly by acting on signal pathways, including Hypoxia inducer factor-1 (HIF-1), Phosphatidylinositol -3- kinase (PI3K/Akt), Pathways in cancer, Tumor necrosis factor (TNF) and Cell cycle. Conclusion  Based on the methodology of network pharmacology, this study preliminarily predicted the major targets and pathways of Agrimonia pilosa in the treatment of colon cancer, providing a direction for further studies.

Key Words:  Agrimonia pilosa; Colon cancer; Network pharmacology; Target; Pathway