摘要
目的:通过网络药理学和分子对接技术探讨异喹啉生物碱(IAs)肝毒性(HT)的可能作用机制。方法:通过互联网科学数据库the web of science,PubMed,Science Direct,Geenmedical收集IAs的候选毒性化合物和靶点;从Genecards Database中获得HT相关靶点,并利用STRING数据库对IAs肝毒性的靶点基因进行分析;Cytoscape软件构建蛋白质-蛋白质相互作用(PPI)网络,CytoHubba插件筛选核心基因;通过Bioinformatics网站对IAs肝毒性的靶点基因进行基因本体(GO)和京都基因与基因组百科全书(KEGG)富集分析。最后,使用Autodock软件对核心毒性化合物和核心基因进行分子对接验证,并用pymol软件就对接结果进行3D可视化分析。结果:互联网科学数据库显示有13种IAs活性成分存在HT;PPI网络和核心靶点分析表明ANXA5、CASP3、CCL5、IL2和PPARG是HT的关键靶点。GO和KEGG分析显示,IAs可通过癌症途径、癌症中的蛋白多糖以及癌症中的微小RNA等通路参与过氧化氢的反应、凋亡过程的正调控等多种生物学过程。此外,分子对接方法证实了IAs的13种生物活性分子与HT靶点高度亲和,其结合活性可能受到化学结构中五碳环所处的位置,所连的基团,以及是否闭环有影响。结论:通过网络药理学和分子对接,从IAs的活性化合物可能通过作用于5个核心基因以及33条信号通路导致肝毒性。
Objective:The mechanism of hepatotoxicity(HT)of isoquinoline alkaloids(IAs)was studied by network pharmacology and molecular docking technology.Method:The candidate toxic compounds and targets of IAs were collected through the web of science,PubMed,ScienceDirect,Geenmedical.HT related targets were obtained from Genecards database,and the target genes of hepatotoxicity of IAs were analyzed through string database.Protein protein interaction(PPI)network was constructed by Cytoscape software,and core genes were screened by Cytohubba plug-in.In addition,Gene Ontology(GO)and Kyoto Encyclopedia of genes and genomes(KEGG)enrichment analysis were carried out on the target genes of hepatotoxicity through bioinformatics website.Finally,Auto dock software was used to verify the molecular docking of core toxic compounds and core genes,and pymol software was used to analyze the docking results in 3D visualization.Result:Internet scientific databases showed 13 active ingredients with HT in IAs.PPI network and core target analysis showed that ANXA5,CASP3,CCL5,IL2 and PPARG were the key targets of HT.GO and KEGG analysis showed that IAs participated in many biological processes such as hydrogen peroxide reaction and positive regulation of apoptosis through cancer pathways,proteoglycans in cancer,and microRNAs in cancer.In addition,molecular docking confirmed the high affinity between the 13 bioactive molecules of IAs and HT targets,and the binding activity may be affected by the chemical structure such as position of the five-carbon ring,the connected groups,and whether closing loop.Conclusion:Based on network pharmacology and molecular docking,the active compounds from IAs may cause hepatotoxicity by acting on 5 core genes and 33 signaling pathways.
作者
梁迪
王辉
谌立巍
陈思敏
LIANG Di;WANG Hui;SHEN Li-wei;CHEN Si-min(School of Pharmacy,Chengdu University of Traditional Chinese Medicine,Chengdu 611137,Sichuan)
出处
《中药与临床》
2022年第6期44-50,69,共8页
Pharmacy and Clinics of Chinese Materia Medica
基金
成都中医药大学青基人才专项(No.QJRC2021012)。
关键词
异喹啉生物碱
肝毒性
网络药理学
分子对接
Isoquinoline alkaloids
hepatotoxicity
network pharmacology
molecular docking
作者简介
梁迪,在读硕士研究生,主要从事中药药理学研究,Tel:13135362582,Email:m13135362582@163.com;通讯作者:陈思敏(1978-),副教授,主要从事中药药理学研究,Email:1774669716@qq.com。
