基于网络药理学和分子对接技术探讨芪藤消浊颗粒治疗慢性肾小球肾炎的作用机制

Mechanism of Qiteng Xiaozhuo granule in the treatment of chronic glomerulonephritis based on network pharmacology and molecular docking technology

目的通过网络药理学与分子对接技术,分析芪藤消浊颗粒治疗慢性肾小球肾炎(CGN)的物质基础及作用机制。方法2021年3—10月,运用TCMSP、TCMID、HERB数据库收集芪藤消浊颗粒的活性成分及靶点信息,应用DrugBank、Gene‐Cards、OMIM、PharmGKB、TTD数据库检索收集CGN疾病基因。对药物和疾病靶点取交集,借助STRING数据库构建蛋白相互作用(PPI)网络,运用Cytoscape软件构建“中药化合物-交集基因”网络、核心基因筛选网络分别获取核心活性成分、核心靶点,利用DAVID数据库进行基因本体论(GO)功能注释及京都基因与基因组百科全书(KEGG)通路富集分析。最后,通过SailVina平台进行Autodock vina分子对接,运用PyMOL软件进行可视化分析,使用PLIP网站确定结合位点。结果获取芪藤消浊颗粒中58种活性成分,核心活性成分可能为槲皮素、山柰酚、雷公藤甲素,CGN疾病基因1847个,药物与疾病交集靶点134个,核心基因筛选网络得到5个核心靶点分别为促分裂原活化蛋白激酶1(MAPK1)、禽肉瘤病毒17的假定转化基因(JUN)、信号转导和转录激活因子3(STAT3)、原癌基因(RELA)、白细胞介素-6(IL-6)。富集分析得到504个GO条目,216条信号通路。分子对接结果表明核心活性成分能够与关键靶点蛋白稳定结合且具有较好的亲和力。结论芪藤消浊颗粒可能主要通过槲皮素、山柰酚、雷公藤甲素等核心活性成分与关键靶点蛋白MAPK1、JUN、STAT3、RELA、IL6结合,参与调控肿瘤坏死因子(TNF)、TOLL样受体、低氧诱导因子-1(HIF-1)、NOD样受体、核转录因子κB(NF-κB)等信号通路来抑制炎症反应、调节免疫功能紊乱从而治疗CGN。

Objective To analyze the material basis and action mechanism of Qiteng Xiaozhuo granule in the treatment of chronic glomerulonephritis(CGN)by network pharmacology and molecular docking technology.Methods From March to October 2021,the ac‐tive components and target information of Qiteng Xiaozhuo granules were collected by TCMSP,TCMID and HERB databases.CGN dis‐ease genes were retrieved and collected from DrugBank,GeneCards,OMIM,PharmGKB,and TTD databases.The intersection of drugs and disease targets were taken,and the protein-protein interaction(PPI)network was constructed based on STRING database.Cyto‐scape software was adopted to construct the"traditional Chinese medicine ingredient-intersection gene"network and core gene screen‐ing network so as to obtain the core active components and core targets respectively.DAVID database was used for Gene Ontology(GO)annotations and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis.Finally,Autodock vina molecular docking was carried out through SailVina platform,PyMOL software was used for visual analysis,and PLIP website was used to deter‐mine the binding sites.Results A total of 58 active components were taken from Qiteng Xiaozhuo granules.The core active compo‐nents might be quercetin,kaempferol and triptolide.There were 1847 CGN disease genes and 134 drug-disease intersection targets.The core gene screening network obtained 5 core targets,namely mitogen-activated protein kinase 1(MAPK1),the putative transform‐ing gene of avian sarcoma virus 17(JUN or Jun proto-oncogene),signal transducer and activator of transcription 3(STAT3),proto-onco‐gene(RELA)and Interleukin 6(IL-6).Totally 504 GO entries and 216 signaling pathways were obtained by enrichment analysis.The results of molecular docking showed that the core active components could stably bind to the key target proteins and had good affinity.Conclusion Qiteng Xiaozhuo granule may be involved in the regulation of tumor necrosis factor(TNF),TOLL-like receptor,hypoxiainducible factor-1(HIF-1),NOD-like receptor and nuclear factor kappa-B(NF-κB)signaling pathways by binding with key target pro‐teins MAPK1,JUN,STAT3,RELA and IL6 through core active components quercetin,kaempferol and triptolide to inhibit inflammato‐ry response and regulate immune dysfunction,so as to treat CGN.