摘要
目的通过网络药理学方法探讨预知子治疗肝癌的潜在作用靶点及相关信号通路,从而预测其可能的作用机制。方法借助中药系统药理学数据库与分析平台(TCMSP)数据库,检索筛选出符合要求的预知子主要活性成分及靶点。借助GeneCards数据库和OMIM数据库检索得到与肝癌相关的作用靶点。然后筛选出药物和疾病的共同作用靶点,获得预知子可能作用于肝癌的基因。利用Cytoscape软件构建"药物-活性成分-疾病-靶点"的中药调控网络,借助STRING数据库构建出蛋白相互作用PPI网络,运用R语言对PPI网络进行核心蛋白的筛选。最后运用R语言对关键靶基因进行GO功能富集分析、KEGG通路富集分析。结果检索筛选出预知子治疗肝癌的活性成分6个(其中4个与肝癌靶点及相关信号通路相关),涉及与肝癌相关靶基因共27个,网络分析结果显示关键靶基因主要包括:CASP3、JUN、CHRM1、ADRA1B、CASP8、CASP9、PTGS2、CHRM2、SLC6A4等。GO功能富集分析显示分子功能主要涉及受体活性、蛋白酶活性、通道活性等,生物学过程主要涉及膜电位的调节、细胞对药物的反应、乙酰胆碱信号通路等。KEGG通路富集分析得到69条通路,涉及神经活性配体-受体相互作用、乙型肝炎、细胞凋亡、钙信号通路、P53信号通路、人免疫缺陷病毒1感染及一些癌症信号通路。结论该文运用网络药理学阐释了预知子抗肝癌的潜在作用靶点及通路,为深入研究预知子抗肝癌的作用机制提供了思路。
Objective The aim of this study is to explore the targets and related signaling pathways of Fructus Akebiae in the treatment of hepatocarcinoma based on network pharmacology,and to predict its potential mechanism.Methods Based on the TCMSP database,the effective active components and targets of Fructus Akebiae were extracted.Through the human genome annotation database(GeneCards)and the online human Mendelian network(OMIM)database,the targets related to hepatocarcinoma were collected.And then the common targets were screened by R language.The common parts were screened out to obtain the potential target genes that overlapped between Fructus Akebiae and hepatocarcinoma.Cytoscape software was used to construct a visual regulatory network map of"drug-active ingredient-disease-target",and a protein-protein interaction network map(PPI)was constructed using the STRING database.Then the R language was used to screen the core protein of the PPI;and the GO enrichment and KEGG enrichment analysis were conducted on the key targets to analyze their potential mechanism of action.Results There were 6 active components and 27 target genes in the treatment of hepatocarcinoma with Fructus Akebiae,and the drug-component-target-disease network showed that the key genes mainly included:CASP3,JUN,CHRM1,ADRA1 B,CASP8,CASP9,PTGS2,CHRM2,SLC6 A4,etc.GO functional enrichment showed that the molecular functions were mainly related to receptor activity,protease activity,channel activity and so on.The biological process mainly involved the regulation of membrane potential,cell response to drugs,acetylcholine signaling pathway and so on.KEGG functional enrichment showed that the enriched pathways mainly included neuroactive ligand-receptor interaction,hepatitis B,apoptosis,calcium signaling pathway,p53 signaling pathway,human immunodeficiency virus 1 infection,and some cancer signaling pathways.Conclusion In this paper,we applied network pharmacology to explain the targets and pathways of Fructus Akebiae against hepatocarcinoma.The results pr
作者
陈文成
王纯
陈涛
胡卫
曾建红
Chen Wencheng;Wang Chun;Chen Tao(Third-Grade Pharmacological Laboratory on Traditional Chinese Medicine,State Administration of Traditional Chinese Medicine,Medical College of China Three Gorges University,Yichang 443002,China)
出处
《华中科技大学学报（医学版）》
CAS
CSCD
北大核心
2021年第4期471-477,共7页
Acta Medicinae Universitatis Scientiae et Technologiae Huazhong
基金
国家自然科学基金资助项目(No.81873148)。
关键词
预知子
肝癌
网络药理学
作用机制
Fructus Akebiae
hepatocarcinoma
network pharmacology
mechanism of action
