摘要
目的应用网络药理学及分子对接技术探究益肾健脾利水方(肾炎舒片)治疗肾小球肾炎的活性成分及分子机制。方法通过中药系统药理数据库和分析平台(TCMSP)查询方中主要的7味中药(苍术、茯苓、白茅根、人参、枸杞子、金银花、蒲公英)的主要活性成分,并对其靶点进行预测。检索GeneCards、OMIM、PharmGKB、TTD、DrugBank数据库。利用UniProt数据库注释所有靶标蛋白。将活性成分作用靶点和疾病靶点交集部分作为肾炎舒片治疗肾小球肾炎的潜在作用靶点,并利用GO数据库和KEGG数据库进行通路富集分析,将得到的核心有效成分与核心靶标进行分子对接。结果筛选出81个活性成分、219个基因靶点、肾小球肾炎相关靶点1952个、116个肾炎舒片治疗肾小球肾炎的潜在靶点蛋白。GO富集分析结果提示:肾炎舒片治疗肾小球肾炎的潜在靶点蛋白,主要参与脂多糖反应、细菌源分子反应、氧化反应以及细胞化学压力反应等生物学过程。KEGG富集分析结果提示:可能的作用通路包括脂质和动脉粥样硬化通路、糖尿病并发症的AGE-RAGE信号通路、乙型肝炎相关通路以及卡波西肉瘤相关疱疹病毒感染通路等。蛋白互作(PPI)网络分析结果显示:肾炎舒片可通过MYC、JUN、MAPK8、FOS、NR3C1、TP53、MAPK14、IL-2、MAPK1、AKT1、TNF、RELA这12个关键靶点治疗肾小球肾炎。分子对接结果提示肾炎舒片主要活性成分与多种治疗肾小球肾炎靶点蛋白均有较好结合(S>4.5)。结论本研究结果提示益肾健脾利水方(肾炎舒片)治疗肾小球肾炎具有多成分、多靶点、多通路的特点,为进一步阐释其药理作用机制及开发新药奠定了研究基础。
Objective To explore the active ingredients and molecular mechanisms of Yishen-Jianpi-Lishui recipe(Shenyanshu tablet,SYST)in the treatment of glomerulonephritis by the network pharmacology and molecular docking methods.Methods Through the analysis platform of Traditional Chinese Medicine Systems Pharmacology(TCMSP),the main active ingredients of the 7 main Chinese medicines(Atractylodes,Poria,Imperata,ginseng,wolfberry,honeysuckle,and dandelion)in the recipe were queried,and their targets were also predicted.The databases were searched including the human gene database(GeneCards),the database of Online Mendelian Inheritance in Man(OMIM),the Pharmacogenetics and Pharmacogenomics Knowledge Base(PharmGKB),the Therapeutic Target Database(TTD),and the drug action target database(DrugBank).The UniProt database was used to annotate all targets proteins.The intersection of the active ingredients′targets and diseases′targets were taken as the potential targets for the treatment of glomerulonephritis by SYST,for which the gene ontology(GO)database and the Kyoto Encyclopedia of Genes and Genomes(KEGG)database were applied for the pathway enrichment analysis,and the core active ingredients and core targets obtained were analyzed with the molecular docking method.Results A total of 81 active ingredients,219 gene targets,1,952 glomerulonephritis-related targets,and 116 potential targets proteins for the treatment of glomerulonephritis with SYST were screened out.The GO enrichment analysis results suggested that the potential targets proteins for the treatment of glomerulonephritis with SYST were mainly involved in the biological processes such as lipopolysaccharide reaction,bacterial-derived molecular reaction,oxidation reaction,and cytochemical pressure reaction.The KEGG enrichment analysis results suggested that possible pathways included the lipid and atherosclerosis pathways,the advanced glycation end products(AGEs)and the receptor for AGE(RAGE)signaling pathways for diabetic complications,hepatitis B-related pathways
作者
金美玲
李典耕
张伟光
尹智炜
杨洪娟
Jin Meiling;Li Diangeng;Zhang Weiguang;Yin Zhiwei;Yang Hongjuan(Department of Nephrology,Beijing Chaoyang Hospital Affiliated to Capital Medical University,Beijing 100020;Department of Scientific Research,Beijing Chaoyang Hospital Affiliated to Capital Medical University,Beijing 100020;Department of Nephrology,First Medical Center of Chinese PLA General Hospital,Chinese PLA Institute of Nephrology,State Key Laboratory of Kidney Diseases,National Clinical Research Center for Kidney Diseases,Beijing Key Laboratory of Kidney Diseases,Beijing 100853;College of Integrated Chinese and Western Medicine,Hebei Medical University,Shijiazhuang 050017,Hebei Province;Department of Nephrology of Integrated Chinese and Western Medicine,First Hospital of Hebei Medical University,Shijiazhuang 050031,Hebei Province,China)
出处
《中华肾病研究电子杂志》
2021年第4期189-197,共9页
Chinese Journal of Kidney Disease Investigation（Electronic Edition）
基金
国家自然科学基金(81900605,81901404)
北京市自然科学基金(7204308)
河北省重点研发计划项目(18277746D)。
关键词
肾益健脾利水方
肾炎舒片
肾小球肾炎
网络药理学
分子对接
Yishen-Jianpi-Lishui recipe
Shenyanshu tablet
Glomerulonephritis
Network pharmacology
Molecular docking
