基于网络药理学和分子对接研究“乌药蜜饮”对治疗结直肠癌的作用  

Effects of Wuyaomi recipe in prevention of colorectal cancer based on network pharmacology and molecular docking

作　　者：余炜[1] 魏丞[2] 余辉[1] 陈娟[1] 郭增清 黄静[1] 陈婧[4] 廖联明[5] YU Wei;WEI Cheng;YU Hui;CHEN Juan;GUO Zeng-qing;HUANG Jing;CHEN Jing;LIAO Lian-ming(Department of Pharmacy,Clinical Oncology School of Fujian Medical University,Fujian Cancer Hospital,Fuzhou 350014,Fujian Province,China;Department of Surgical Oncology,Clinical Oncology School of Fujian Medical University,Fujian Cancer Hospital,Fuzhou 350014,Fujian Province,China;Department of Medical Oncology,Clinical Oncology School of Fujian Medical University,Fujian Cancer Hospital,Fuzhou 350014,Fujian Province,China;Department of Pharmacy,The First Affiliated Hospital of Xiamen University,Xiamen 361022,Fujian Province,China;Center of Laboratory Medicine,Union Hospital of Fujian Medical University,Fuzhou 350001,Fujian Province,China)

机构地区：[1]福建医科大学肿瘤临床医学院,福建省肿瘤医院药剂科,福建福州350014 [2]福建医科大学肿瘤临床医学院,福建省肿瘤医院肿瘤外科,福建福州350014 [3]福建医科大学肿瘤临床医学院,福建省肿瘤医院肿瘤内科,福建福州350014 [4]厦门大学附属第一医院杏林分院药剂科,福建厦门361022 [5]福建医科大学附属协和医院中心实验室,福建福州350001

出　　处：《中国临床药理学杂志》2023年第23期3486-3490,共5页The Chinese Journal of Clinical Pharmacology

摘　　要：目的通过网络药理学及分子对接探究“乌药蜜饮”方的有效成分及其作用于结直肠癌的主要生物过程和信号通路,阐明其作用机制。方法通过中药系统药理学数据库与分析平台预测中药的有效成分和相关靶点。从人类孟德尔遗传综合数据库、遗传药理学与药物基因组学数据库和基因名片数据库等5个数据库收集结直肠癌相关疾病基因。用Cytoscape 3.8.2软件构建蛋白质相互作用网络的“有效成分-疾病靶点”网络,获取和分析核心靶点和关键成分。对核心靶点基因进行京都基因与基因百科全书通路富集分析。最后用AutoDock Vina 1.1.2软件将中药有效成分与通路上的核心基因靶点蛋白进行分子对接。结果最终筛选得到4种中药有效成分(木犀草素、槲皮素、黄芩素、汉黄芩素)和包括细胞肿瘤抗原P53、丝/苏氨酸蛋白激酶1、丝裂原活化蛋白激酶1等14个对应的核心靶点。核心靶点基因通过调控癌症相关通路、磷脂酰肌醇3激酶-丝/苏氨酸激酶通路等肿瘤相关信号通路,诱导细胞周期阻滞和凋亡,从而达到治疗结肠癌的目的。进一步的分子对接结果表明,关键中药有效成分木犀草素与多个核心靶点蛋白表现出很强的结合能力。结论“乌药蜜饮”方中多个中药有效成分可通过多靶点和多通路的途径发挥治疗结肠癌的功效。Objective To explore the effective components of Wuyaomi recipe and the main biological processes and signal pathways involved in the therapeutic mechanism of the recipe in treatment of colorectal cancer through network pharmacology and molecular docking approaches.Methods The potential compounds and related target genes were analyzed through the traditional Chinese medicine system pharmacology database and analysis platform.Colorectal cancer related genes were from five databases including online Mendelian inheritance in man,PharmGKB and Genecards databases.Cytoscape 3.8.2 software was used to construct the"ingredient-disease-target"network and the core targets and key components were obtained and analyzed.The gene annotation tool of DAVID database was used to perform Kyoto encyclopedia of genes and genomes pathway enrichment analysis.Finally,AutoDock Vina1.1.2 software was used to perform molecular docking.Results We finally identified 4 active ingredients(luteolin,quercetin,baicalein,wogonin)and 14 core target genes,including cellular tumor antigen p53,ARC-alpha serine/threonine-protein kinase 1,mitogen-activated protein kinase 1,etc.These core target genes were mainly related to phosphatidylinositol 3 kinase-serine/threonine kinase signaling pathway and other tumorrelated signaling pathways are regulated to induce cell cycle arrest and apoptosis,thus achieving the purpose of colorectal cancer treatment.The results of molecular docking suggested that luteolin was capable of binding with multiple core target proteins under natural condition.Conclusion We found that several components of Wuyaomi recipe were involved in treating colorectal cancer through multiple targets and multiple pathways.

关 键 词：乌药蜜饮 结直肠癌 网络药理学 分子对接 

分 类 号：R28[医药卫生—中药学]