摘要
【目的】基于网络药理学构建两面针抗肿瘤的“活性成分-抗肿瘤靶点-抗肿瘤通路”等网络关系,预测其抗肿瘤的作用靶点并对其作用机制进行研究分析。【方法】以口服利用度(OB)及类药性(DL)为限制条件在中药系统药理学分析平台(TCMSP)数据库筛选出两面针主要活性化学成分,在Pharmmapper服务器上筛选和建立两面针靶点数据库。通过OMIM及其他数据库进行抗肿瘤相关基因及蛋白靶点筛选。使用R4.2.1软件做出两面针活性成分、靶点基因和肿瘤。靶点基因相交情况筛选两面针作用靶点。通过Cytoscape3.6.1软件Merge及Union功能,建立了两面针“有效成分--肿瘤靶点”的可视化交互网络。利用STRING数据库构建抗肿瘤靶点之间的交互网络、PPI网络,利用DAVID数据库对靶蛋白进行KEGG通路注释分析,富集出生物通路,构建出“活性成分-抗肿瘤靶点-抗肿瘤通路”网络。选择其中一个关联度较高的活性化合物作为配体、KEGG富集结果中较为显著的信号通路所涉及靶点作为受体,对活性成分与核心靶蛋白进行分子对接验证。【结果】经筛选和分析获得两面针活性成分21个,抗肿瘤靶点14个,包括EGFR、ESR2、ESR1、AR、GSTP1、CYP19A1、PIK3CG、MAPK1等。富集出43条生物通路两面针抗肿瘤的可能通路包括化学致癌-受体活化、雌激素、PI3K-Akt、乳腺癌信号通路等。活性化合物MOL005103作为配体,EGFR作为受体,分子对接验证显示,两者有着较好的结合活性,对接得分7.4766。【结论】结果表明两面针是通过多成分和多靶点的相互作用起到抗肿瘤作用的,也是调控多条通路共同干预实现的,但关键的靶标和具体的调控机制尚待进一步的实验研究加以探索及验证。
【Objective】Based on network pharmacology,the network relationship of“active ingredients-antitumor targets-antitumor pathways,etc.”for the anti-tumor effect of Zanthoxylum nitidum(Roxb.)DC.was constructed,and its anti-tumor target and mechanism were predicted and analyzed.【Method】The main active chemical components of Zanthoxylum nitidum were screened out in the Analysis Platform Database of Traditional Chinese Medicine Systems Pharmacology(TCMSP)with oral bioavailability(OB)and drug-likeness(DL)as the limiting conditions,and the target database of Zanthoxylum nitidum was screened and established on the Pharmmapper server.Anti-tumor related genes and protein targets were screened by OMIM and other databases.R4.2.1 software was used to make the active components,target genes and tumors of Zanthoxylum nitidum.The intersection of target genes was screened for targets of Zanthoxylum nitidum.Through the Merge and Union functions of Cytoscape 3.6.1 software,a visual interactive network of“active ingredients-tumor targets”of Zanthoxylum nitidum was established.The STRING database was used to construct the interaction network and PPI network between anti-tumor targets.The KEGG pathway annotation analysis of target proteins was performed using the DAVID database.Biological pathways were enriched,and a network of“active ingredients-antitumor targets-antitumor pathways”was constructed.One of the active compounds with high correlation was selected as the ligand,and the target involved in the more significant signaling pathway in the KEGG enrichment result was used as the receptor.【Result】After screening and analysis,21 active ingredients and 14 anti-tumor targets were obtained from Zanthoxylum nitidum,including EGFR,ESR2,ESR1,AR,GSTP1,CYP19A1,PIK3CG,MAPK1,etc.A total of 43 biological pathways were enriched.Possible anti-tumor pathways of Z.nitidum Maxim include chemical carcinogenesis receptor activation,estrogen,PI3K Akt,breast cancer signal pathway,etc.The active compounds MOL005103 acts as a ligand
作者
周媛
岑怡
文裕
陈睿
梁雁
粟华生
王柳萍
奉建芳
Zhou Yuan;Cen Yi;Wen Yu;Chen Rui;Liang Yan;Su Hua-sheng;Wang Liu-ping;Feng Jian-fang(Guangxi Agricultural Vocational Technical University,Nanning,Guangxi 530007,China;Youjiang Medical University for Nationalities,Baise,Guangxi 533000,China;Guangxi University of Chinese Medicine,Nanning,Guangxi 530200,China;Guangxi Engineering and Technology Research Center for the Development of Proprietary Chinese Medicine and Ethnic Medicine,Nanning,Guangxi 530200,China;Jiangxi University of Chinese Medicine,Nanchang,Jiangxi 330004,China)
出处
《广西农学报》
2023年第5期68-78,97,共12页
Journal of Guangxi Agriculture
基金
国家重点研发计划项目(2019YFC1712304)
广西中医药管理局科研课题(GXZYZ20210068)
2020年广西农业科技自筹经费项目(Z202004)
2021年广西农业职业技术大学科学研究与技术开发项目(YKJ2135)。
关键词
两面针
网络药理学
活性成分
作用靶点
抗肿瘤机制
Zanthoxylum nitidum(Roxb.)DC.
network pharmacology
active ingredient
action target
anti-tumor mechanism
