摘要
背景:大量研究发现“乳香-没药”是中药复方治疗膝骨关节炎的常用配伍药对,但其药理机制尚不明确。目的:利用网络药理学技术探讨“乳香-没药”作为中医临床治疗痹病的常用配伍药对治疗膝骨关节炎的作用靶点及其相关作用机制。方法:使用TCMSP中药系统药理学数据库与分析平台收集乳香、没药的化学成分,根据药物生物口服利用度≥30%,类药性≥0.18对乳香、没药可能的生物活性成分进行筛选,并通过蛋白质数据库(Uniprot)筛选出各活性成分可能存在的靶点。查询GeneCards、OMIM、TTD、DrugBank数据库挖掘膝骨关节炎相关基因靶点,将两者取交集后获取疾病-药物蛋白靶基因。将获得的关键靶点基因上传至STRING数据库计算分析,筛选出重要的关键基因构建蛋白质间相互作用网络,构建PPI网络图。采用Cytoscape软件绘制药物-靶点和疾病-靶点可视化网络图,并进一步借助DAVID在线工具进行GO分析和KEGG通路富集分析。结果与结论:①获得乳香生物活性成分8个,没药生物活性成分45个,同时检测出乳香、没药药物靶点蛋白412个,膝骨关节炎相关基因1889个,药物与疾病共有靶点105个;②蛋白互作网络发现AKT1、TP53、IL6、TNF、JUN、MAPK1等可能是“乳香-没药”治疗膝骨关节炎的关键靶点;③富集分析确定了66个GO条目,涉及到细胞对缺氧的反应、上皮细胞增殖的负调控、免疫反应、胰岛素刺激的细胞反应、成纤维细胞增殖的正调控等;④KEGG通路富集分析确定了95条相关信号通路,涉及到炎症、细胞凋亡、细胞衰老等。利用David富集分析显示乳香-没药干预膝骨关节炎的关键靶点主要与炎症反应、细胞凋亡与免疫系统等生物过程有关;⑤结果表明,“乳香-没药”药对治疗膝骨关节炎具有多途径、多靶点作用的特点,主要起到抗炎镇痛的作用,初步揭示了其作用的关键靶点及涉及的生物�
BACKGROUND:“Ruxiang-Moyao”is a common combination of traditional Chinese medicine in the clinical treatment of knee osteoarthritis.However,the pharmacological mechanism is not yet clear.OBJECTIVE:Using network pharmacology technology to explore the therapeutic target of“Ruxiang-Moyao”as a commonly used traditional Chinese medicine for clinical treatment of arthromyodynia in the treatment of knee osteoarthritis and the relevant mechanism.METHODS:The chemical constituents of“Ruxiang-Moyao”were collected by TCMSP pharmacology database and analysis platform,and the possible bioactive constituents of frankincense and myrrh were screened according to the biological oral availability≥30%and class drug properties≥0.18.The possible targets of each active constituent were screened out using the protein database(Uniprot).GeneCards,OMIM,TTD and DrugBank databases were consulted to mine knee osteoarthritis-associated gene targets.The disease-drug protein target genes were obtained after the intersection of the above-mentioned screening data.The STRING database calculation and analysis algorithm was used to screen out important key genes to build a protein-protein interaction network,and the key target genes were uploaded to the PPI network graph.Cytoscape software was used to map the drug-target and disease-target visualization network,and DAVID online tool was further used for gene ontology(GO)analysis and Kyoto Encyclopedia of Genes and Gnomes(KEGG)pathway enrichment analysis.RESULTS AND CONCLUSION:Eight bioactive constituents of frankincense and 45 bioactive constituents of myrrh were obtained.At the same time,412 target proteins of“Ruxiang-Moyao,”1889 genes related to knee osteoarthritis and 105 co-targets of drugs and diseases were detected.The protein-protein interaction network found that AKT1,TP53,IL6,TNF,JUN,and MAPK1 might be the key targets of“Ruxiang-Moyao”in the treatment of knee osteoarthritis.The GO enrichment analysis identified 66 GO items,which are involved in cell response to hypoxia
作者
曹旭含
白子兴
孙承颐
杨艳军
孙卫东
Cao Xuhan;Bai Zixing;Sun Chengyi;Yang Yanjun;Sun Weidong(Wangjing Hospital of China Academy of Chinese Medical Sciences,Beijing 100102,China;Beijing University of Chinese Medicine,Beijing 100029,China)
出处
《中国组织工程研究》
CAS
北大核心
2021年第5期746-753,共8页
Chinese Journal of Tissue Engineering Research
基金
首都临床诊疗技术研究及示范应用项目(Z191100006619024),项目负责人:孙卫东
国家自然科学基金项目(81373802),项目负责人:孙卫东
北京市自然科学基金项目(7172244),项目负责人:孙卫东。
关键词
膝
骨关节炎
乳香
没药
网络药理学
通路
蛋白
基因
机制
knee
knee osteoarthritis
frankincense
myrrh
network pharmacology
pathway
protein
gene
mechanism
