摘要
目的:采用数据挖掘、GEO基因芯片挖掘、网络药理学、分子对接技术及文献验证方法,分析国家专利复方治疗肝癌的用药规律及其核心药对的作用机制。方法:收集国家知识产权数据库中治疗肝癌的中药复方,使用中医传承计算平台V3.0软件进行用药、组方规律分析,并筛选出其中使用频数最高的核心药对。从GEO数据库下载肝癌的基因芯片数据集,利用R软件筛选出显著性差异基因,从TCMSP、SymMap、PharmMapper等数据库获取核心药对的活性成分、药物靶点,运用Cytoscape软件、R软件,对药物-疾病交集靶点进行PPI、GO、KEGG分析,使用PyMOL、AutoDockTools1、AutoDock Vina等软件对活性成分-核心靶点进行分子对接验证。结果:共获得315首专利复方,549味中药,使用频数最高的是黄芪、白花蛇舌草、半枝莲、白术、柴胡等,性味运用最多的是寒性、温性、苦味、甘味,中药功效以补虚药、清热药、活血化瘀等为主,核心药对为半枝莲-白花蛇舌草。得到肝癌显著性差异基因1423个,筛选出药物-疾病交集靶点80个。PPI拓扑分析得出的核心靶点有ESR1、AR、TYMS、CDK1、CYP1A1、MMP9、CCNB1、IGF1、PTGS2等。GO功能富集分析主要涉及药物反应、酒精代谢过程、类花生酸代谢过程、环氧酶P450途径、分泌颗粒腔、蛋白激酶活性等,KEGG通路分析主要富集在化学致癌作用通路、细胞色素P450对外源性物质的代谢通路、p53信号通路、FoxO信号通路等。分子对接验证显示各主要活性成分与核心靶点间结合能均<-5.0 kcal/mol。结论:当代医家治疗肝癌时重视补益正气,并配以清热活血之法,常从肝脾进行论治,其使用频数最高的核心药对(半枝莲-白花蛇舌草)治疗肝癌具有多途径、多成分、多功能的作用机制。
Objective:To explore the regularity and molecular mechanism of national patented compound prescription in the treatment of liver cancer by data mining,GEO gene chip mining,network pharmacology and molecular docking technology.Methods:The traditional Chinese medicine compounds for the treatment of liver cancer were collected from the national intellectual property database,and the traditional Chinese medicine inheritance and calculation platform V3.0 software was applied for medication and prescription rule analysis,to select the core drug pairs with the highest frequency of use.The gene chip dataset of liver cancer was downloaded from the GEO database and significant differential genes were selected by R software.The active components and drug targets of the core drug pair were obtained from the databases of TCMSP,SymMap and PharmMapper.Cytoscape software and R software were used for PPI,GO for KEGG analysis to get the drug-disease intersection targets.Molecular docking validation was performed on the active component-core targets using PyMOL,AutoDockTools1 and AutoDock Vina software.Results:A total of 315 patented compounds were obtained,involving 549herbs.The most frequently used ones were Hunagqi(Astragalus Membranaceus),Baihua Sheshecao(Hedyotis Diffusa),Banzhilian(Scutellaria Barbata),Baizhu(Atractylodes Macrocephala)and Chaihu(Bupleurum Chinense),and the most used ones were cold,warm,bitter and sweet herbs.The efficacy of traditional Chinese medicine is mainly tonifying deficiency,clearing heat and promoting blood circulation and removing blood stasis.The core drug pair is Banzhilian(Scutellaria Barbata)-Baihua Sheshecao(Hedyotis Diffusa).A total of 1423 significant differential genes of liver cancer were obtained,and 80 targets of drug-disease intersection were selected.The core targets derived from PPI topological analysis are ESR1,AR,TYMS,CDK1,CYP1A1,MMP9,CCNB1,IGF1and PTGS2.GO functional enrichment analysis mainly involves drug reactions,alcohol metabolic processes,eicosanoid metabolic processes,cyclooxygenase P450 pathways,secretory granule lumen and protein kinase activity.And KEGG pathway analysis is mainly enriched in chemical carcinogenic pathways,cytochrome P450 metabolic pathways to xenobiotics,p53 signaling pathways and FoxO signaling pathways.Molecular docking validation showed that the binding energy between each major active ingredient and the core target was<-5.0 kcal/mol.Conclusion:Contemporary physicians pay attention to tonifying the vital Qi in the treatment of liver cancer,and apply the method of clearing heat and activating blood circulation,often from the liver and spleen for treatment.Banzhilian(Scutellaria Barbata)-Baihua Sheshecao(Hedyotis Diffusa),the core drug pair with the highest frequency,treats liver cancer from multi-way,multi-component and multifunctional mechanism of action.
作者
姚元谦
吕建林
柳琳琳
王光耀
杨坤
YAO Yuan-qian;LYU Jian-lin;LIU Lin-lin;WANG Guang-yao;YANG Kun(Guangxi University of Traditional Chinese Medicine,Nanning Guangxi 530001,China;The First Affiliated Hospital of Guangxi University of Traditional Chinese Medicine,Nanning Guangxi 530023,China)
出处
《中医药导报》
2022年第4期131-137,共7页
Guiding Journal of Traditional Chinese Medicine and Pharmacy
基金
国家自然科学基金项目(81860839)
广西自然科学基金项目(2020GXNSFAA238020)
广西研究生教育创新计划资助项目(YCXJ2021059,YCBZ2019035)。
关键词
肝癌
国家专利中药复方
作用机制
分子对接
数据挖掘
liver cancer
national patented compound prescription
mechanism of action
molecular docking
data mining
作者简介
通信作者:吕建林,E-mail:lvjianlin2009@163.com。
