基于网络药理学从铁死亡途径探究七味参地颗粒治疗慢性肾小球肾炎的作用机制
Mechanism of Qiwei Shendi granules for chronic glomerulonephritis through ferroptosis pathway based on network pharmacology
徐先进 1胡文杰 2秦秀娟2
作者信息
- 1. 中国科学技术大学附属第一医院离子医学中心(合肥离子医学中心)药剂科,合肥 230088
- 2. 安徽中医药大学第一附属医院药学部,合肥 230031
- 折叠
摘要
目的 基于网络药理学和在体实验从铁死亡途径探究七味参地颗粒治疗慢性肾小球肾炎(CGN)的有效性及作用机制.方法 运用GeneCards、OMIM、DrugBank数据库筛选CGN相关疾病靶点,TCMSP、HERB、BATMAN-TCM数据库筛选七味参地颗粒有效成分和靶标,FerrDb数据库筛选铁死亡相关靶点,利用Cytoscape软件构建了活性成分-作用靶点和蛋白质-蛋白质相互作用(PPI)网络图,使用R语言进行GO富集和KEGG通路分析,采用AutoDockTools 1.5.7进行分子对接分析,采用Western blot技术检测CGN小鼠肾脏组织中PPARA、MAPK14、HRAS和PTGS2的表达.结果 筛选出1896个CGN疾病靶点,564个铁死亡靶点,33种七味参地颗粒药物活性成分,对应405个靶标,三者交集靶点共17个.采用MCODE,Degree,MCC,DMNC,MNC,EPC,EcCentricity,Closeness,Radiality,BottleNeck 10 种算法筛选出 PPARA、MAPK14、HRAS及PTGS2这4个核心靶蛋白,分子对接结果显示七味参地颗粒药物活性成分与核心靶蛋白均有良好的结合能力,动物实验结果表明七味参地颗粒可逆转4个核心靶蛋白的表达.结论 七味参地颗粒可能通过调控PPARA、MAPK14、HRAS及PTGS2从铁死亡途径发挥治疗CGN的作用.
Abstract
Objective To determine the effectiveness and mechanism of Qiwei Shendi granules in the treatment of chronic glomerulonephritis(CGN)via ferroptosis based on network pharmacology.Methods GeneCards,OMIM,DrugBank,TCMSP,HERB,BATMAN-TCM and FerrDb databases were screened to obtain CGN-related disease targets,active ingredients and targets of Qiwei Shendi granules and ferroptosis-related targets.Cytoscape software was used to construct network of protein-protein interaction(PPI)and active component-action target.GO enrichment and KEGG pathways were conducted with R language.Molecular docking was performed with AutoDockTools 1.5.7.The expression of PPARA,MAPK14,HRAS and PTGS2 were determined in CGN-mice kidney tissues by Westem blot.Results Totally 1896 CGN-related disease targets,564 ferroptosis targets,33 compounds and 405 targets from Qiwei Shendi granules were screened.Totally 17 intersected targets were obtained,which could be potentially therapeutic targets.Four core targets(PPARA,MAPK14,HRAS and PTGS2)in the network were screened with MCODE,Degree,MCC,DMNC,MNC,EPC,EcCentricity,Closeness,Radiality,and BottleNeck algorithms.All docking results showed that the key ingredients in Qiwei Shendi granules had strong binding activity with the core targets.In addition,the four core protein expression changes were reversed in CGN-mice after the treatment with Qiwei Shendi granules.Conclusion Qiwei Shendi granules in regulating CGN via ferroptosis may be related to PPARA,MAPK14,HRAS and PTGS2.
关键词
七味参地颗粒/慢性肾小球肾炎/网络药理学/铁死亡/分子对接Key words
Qiwei Shendi granule/chronic glomerulonephritis/network pharmacology/ferroptosis/molecular docking引用本文复制引用
基金项目
国家自然科学基金青年项目(82104613)
出版年
2024
NETL
NSTL
万方数据