基于数据挖掘和网络药理学研究中药免疫增强剂的作用机制及用药规律

Study on the Medication Rule and Action Mechanism of Traditional Chinese Medicine Immune Enhancer Based on Data Mining and Network Pharmacology

目的采用数据挖掘的方法探究复方专利处方中用于增强免疫力的中药配伍规律,并运用网络药理学、分子对接技术分析其中核心药物的潜在作用机制。方法挖掘国家知识产权局中药增强免疫力的复方专利数据,进行中药频次、关联规则以及复杂网络分析,并筛选出核心药物。利用TCMSP平台筛选核心药物活性成分并进行靶点预测,于疾病数据库OMIM、DrugBank、GeneCards、Uniprot筛选免疫力相关靶点,获取核心中药与免疫力的交集靶点;对交集靶点进行蛋白互作(PPI)分析和基因本体(GO)功能及京都基因与基因组百科全书(KEGG)通路富集分析。使用分子对接技术对药物活性成分、关键靶点进行验证。结果分析中药复方专利得出5味核心药物:黄芪、人参、枸杞子、茯苓、当归,有效活性成分对应靶点214个,1784个免疫力相关靶点,交集靶点55个,关键作用靶点有RELA、TNF、TP53、IL-6。GO分析结果显示主要调控对细菌起源分子的反应、对脂多糖的反应、对生物刺激的反应等。KEGG通路160条,主要涉及脂质与动脉粥样硬化、南美洲锥虫病、TNF信号通路、癌症通路等多条信号通路。分子对接结果显示,槲皮素、山柰酚能较好地与RELA、TNF、TP53、IL-6进行结合。结论专利文献中增强免疫力的中药以补虚药为主,主要有效成分为槲皮素、山柰酚等化合物,以RELA、TNF、TP53、IL-6为关键靶点,通过脂质和动脉粥样硬化、南美洲锥虫病、TNF信号通路、癌症通路等多条通路发挥增强免疫力的作用。

OBJECTIVE To explore the compatibility rules of traditional Chinese medicines used to enhance immunity in compound patent prescriptions using data mining method,and analyze the potential mechanism of action of core drugs by network pharmacology and molecular docking technology.METHODS The patent data of the immunity enhancing compound of traditional Chinese medicine from the State Intellectual Property Office was mined,the frequency of traditional Chinese medicine,association rules and complex network were analyzed,and core drugs were screened.The TCMSP platform was used to screen the active ingredients of core drugs and predict the targets.Immune-related targets were screened from disease databases OMIM,DrugBank,GeneCards and Uniprot to obtain the intersection targets of core Chinese medicine and immunity.Protein interaction(PPI)analysis and gene ontology(GO)function and pathway enrichment analysis of Kyoto Encyclopedia of Genes and Genomes(KEGG)were performed for intersection targets.Molecular docking technology was used to verify the active ingredients and key targets of the drug.RESULTS According to the analysis of Chinese herbal compound patents,five core drugs were obtained:Astragalus,ginseng,Wolfberry,poria,Angelica.The effective active ingredients corresponding to 214 targets,1784 immune-related targets,55 intersection targets,the key action targets are RELA,TNF,TP53,IL-6.The results of GO analysis showed that the main regulation aspects were the response to bacteria origin molecules,the response to lipopolysaccharide,and the response to biological stimuli.There were 160 KEGG pathways,mainly involving lipid and atherosclerosis,Chagas disease,TNF signaling pathway,cancer pathway and other signaling pathways.The molecular docking results showed that quercetin and kaempferol could bind to RELA,TNF,TP53 and IL-6.CONCLUSION The traditional Chinese medicines used in the patent literature to enhance immunity are mainly deficiency tonic drugs,and the main effective components are quercetin,kaempferol and other compounds.RELA,TNF,TP53 and IL-6 are the key targets,which play the role of enhancing immunity through multiple pathways such as lipid,atherosclerosis,Chagas disease,TNF signaling pathway and cancer pathway.