基于网络药理学和分子对接探讨痛风舒片治疗痛风的作用机制

Mechanism of Tongfengshu Tablets in treatment of gout based on network pharmacology and molecular docking

目的采用网络药理学和分子对接探讨痛风舒片治疗痛风的潜在作用机制。方法检索中药系统药理学分析平台挖掘痛风舒片关键成分和对应靶点;检索PharmGKB、GeneCards、OMIM、TTD、DrugBank数据库,筛选痛风疾病靶点,使用R软件Venn包,获取痛风舒片与痛风的交集靶点基因。使用Cytoscape 3.8.0软件构建“中药复方成分–靶点”网络图并筛选药物核心成分;使用String平台获取交集靶点基因的蛋白互作(PPI)网络,并使用Cytoscape 3.8.0软件筛选核心靶点基因。应用R软件对交集靶点基因进行GO功能和KEGG通路富集分析,应用AutoDock Vina软件进行分子对接。结果共挖掘出痛风舒片关键成分38种,对应靶点164个,痛风疾病靶点1554个,二者交集靶点基因66个。筛选出核心成分6种(槲皮素、β-谷甾醇、芦荟大黄素、高车前素、泽兰黄醇素、海波拉亭),核心靶点基因6种[V-rel网状内皮细胞过多症病毒癌基因同源物A(RELA)、白细胞介素-1β(IL-1β)、蛋白激酶B1(AKT1)、丝裂原活化蛋白激酶1(MAPK1)、NF-κB抑制因子α(NFKBIA)、肿瘤蛋白p53(TP53)]。GO功能共富集1963个条目,其中生物过程1830个(涉及对脂多糖的反应等),细胞组分27个(涉及膜筏等),分子功能106个(涉及磷酸酶结合等);KEGG通路共富集154个条目,如白细胞介素(IL)-17、肿瘤坏死因子(TNF)等信号通路。所有核心成分与核心靶点蛋白的结合能均<−5 kcal/mol,大部分结合能<−7 kcal/mol。结论痛风舒片中核心成分槲皮素、β-谷甾醇、芦荟大黄素等可通过作用于RELA、IL-1β、AKT1等核心靶点基因,对IL-17、TNF等信号通路进行调控,从而发挥治疗痛风的作用。

Objective To explore the potential mechanism of Tongfengshu Tablets in treatment of gout by network pharmacology and molecular docking.Methods Key components and corresponding targets of Tongfengshu Tablets were explored by searching pharmacology analysis platform of TCM system.Target genes of gout disease were obtained by searching PharmGKB,GeneCards,OMIM,TTD,and DrugBank databases,the intersection target genes of Tongfengshu Tablets and gout were obtained by Venn package of R software.The network diagram of“TCM compound component-target”was constructed and the drug core components was screened by Cytoscape 3.8.0 software.The protein interaction network of intersecting target genes was obtained using String platform,and the core target genes were screened by Cytoscape 3.8.0 software.GO function and KEGG pathway enrichment analysis were performed on the intersection target genes by R software and molecular docking was performed by AutoDock Vina software.Results A total of 38 key components and 164 corresponding targets of Tongfengshu Tablets were excavated,1554 targets of gout disease were excavated,there were 66 intersection target genes.Six core components(quercetin,β-sitosterol,aloe-emodin,dinatin,eupatin,and hypolaetin)and six core target genes(RELA,IL-1β,AKT1,MAPK1,NFKBIA,and TP53)were screened out.A total of 1963 items were enriched in GO function,including 1830 biological processes(involving reaction to lipopolysaccharide,etc.),27 cell components(involving membrane raft,etc.)and 106 molecular functions(involving phosphatase binding,etc.).A total of 154 items were enriched in KEGG pathway,such as interleukin(IL-17),tumor necrosis factor(TNF)and other signaling pathways.The binding energies of all core components and core target proteins were<−5 kcal/mol,and most of them were<−7 kcal/mol.Conclusion The core components of Tongfengshu Tablets,including quercetin,β-sitosterol,aloe-emotin,ect.,can regulate Il-17,TNF and other signaling pathways by acting on core target genes such as RELA,IL-1β,AKT1,etc.,so as to play a role in the treatment of gout.