摘要
目的基于网络药理学方法探讨黄芪-莪术药对对胃癌前病变(GPL)的作用机制。方法通过中药系统药理学分析平台(TCMSP)获取黄芪、莪术化学成分,以口服生物利用度(OB)≥30%及类药性(DL)≥0.18为条件,结合文献研究筛选出黄芪-莪术药对的主要活性成分;通过TCMSP及Swiss Target Prediction查找筛选其活性成分的对应靶点,利用UniProt数据库查询靶点蛋白对应的人类基因。通过Genecards数据库收集有关GPL的靶点,映射至黄芪-莪术药对活性成分靶点基因,构建黄芪-莪术药对活性成分-靶点网络,利用STRING网站构建交集靶点蛋白相互作用网络(PPI),选出关键靶点基因。将共同靶基因通过Enricher数据库进行GO功能富集与KEGG生物通路富集分析,并利用Cytoscape 3.6.1软件构建靶点-通路网络。结果共检索出166个化合物,筛选得到黄芪-莪术药对活性成分28个,共同靶基因112个,PPI网络中度值≥30的关键基因有26个;GO生物学过程相关条目45条、分子功能相关条目9条及细胞组分相关条目2条;KEGG通路共18条,涉及癌症通路、PI3K-Akt信号通路及p53信号通路等。结论黄芪-莪术药对可能通过多成分、多靶点、多途径参与调控肿瘤细胞增殖与凋亡等多种生理过程,发挥对GPL的干预作用。
Objective To investigate the active ingredients and mechanisms of Astragali radix-Curcumae rhizoma herb pair in treating gastric precancerous lesions(GPL)based on the network pharmacology.Methods The main active ingredients of Astragali radix-Curcumae rhizoma herb pair were obtained by the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)website with the criteria based on oral bioavailability(OB)≥30%,drug-like(DL)≥0.18,combined with related literatures.The corresponding targets of the active ingredients were screened by the TCMSP and Swiss Target Prediction,and the UniProt database was used to query the human gene corresponding to each target protein.The targets of GPL were collected by Genecards database,mapped to the target genes of the active ingredients of Astragali radix-Curcumae rhizoma herb pair,and the active components-target network were constructed.Interactive protein-protein interaction network(PPI)was constructed by STRING website.The common target genes were subjected to gene ontology(GO)enrichment and Kyoto encyclopedia of genes and genomes(KEGG)pathway enrichment analyses by Enricher database.The target-pathway network was constructed using Cytoscape 3.6.1 software.Results 166 compounds,28 active components and 112 common target genes of Astragali radix-Curcumae rhizoma herb pair were obtained,as well as 26 key genes with a value of≥30 in the PPI network were selected.There were 45 GO terms related to biological process in GO enrichment analysis.Enrichment analysis revealed that,there were 18 KEGG pathways,including pathways in cancer,PI3 K-Akt signaling pathway,p53 signaling pathway,etc.Conclusion Astragali radix-Curcumae rhizoma herb pair may involve in various physiological processes such as tumor cell proliferation and apoptosis to exert an intervention effect on GPL by multiple components,multiple targets and multiple pathways.
作者
李嘉丽
杨泽虹
杨良俊
李思怡
刘伟
刘洋
潘华峰
LI Jiali;YANG Zehong;YANG Liangjun;LI Siyi;LIU Wei;LIU Yang;PAN Huafeng(Science and Technology Innovation Center,Guangzhou University of Chinese Medicine,Guangzhou 510405 Guangdong,China)
出处
《中药新药与临床药理》
CAS
CSCD
北大核心
2019年第12期1434-1441,共8页
Traditional Chinese Drug Research and Clinical Pharmacology
基金
广东省普通高校特色创新类项目（2018KTSCX040）
广东省自然科学基金项目（2017A030313845）
广州市科技计划项目（201803010055）
国家自然科学基金项目（81673946）
关键词
黄芪
莪术
网络药理学
胃癌前病变
靶点
通路
作用机制
Astragali radix
Curcumae rhizoma
network pharmacology
gastric precancerous lesions
targets
pathways
mechanism
作者简介
李嘉丽,女,硕士研究生,研究方向:中医药防治胃癌前病变研究,Email:1007008149@qq.com;通信作者:潘华峰,女,教授,研究方向:中医药防治胃癌前病变研究,Email:gzphf@l26.com。
