“土茯苓-百合”药对治疗痛风的网络药理学研究

A study on Tufuling-Baihe couplet medicinals in the treatment of gout based on network pharmacology

背景:“土茯苓-百合”药对治疗痛风的临床应用广泛,取得了良好的疗效,但作用机制尚不明确。目的:基于网络药理学方法研究“土茯苓-百合”药对治疗痛风的分子作用机制。方法:通过中药系统药理学数据库与分析平台(TCMSP),以口服生物利用度及类药性为参数,筛选“土茯苓-百合”药对主要活性成分及作用靶点。应用Gene Cards、OMIM、TTD、Pharm Gkb、Drug Bank数据库预测痛风性关节炎的相关靶点。通过维恩图获取“土茯苓-百合”药对与痛风性关节炎的共同靶点。运用Cytoscape 3.9.0软件绘制中药-成分-疾病-靶点调控网络,利用STRING数据库进行蛋白质-蛋白质相互作用网络的构建与分析。最后通过R语言进行基因本体论(GO)富集分析和京都基因与基因组百科全书(KEGG)通路分析。结果:获得“土茯苓-百合”药对活性成分20个,对应作用靶点185个,痛风疾病靶点410个,潜在共同作用靶点38个。“土茯苓-百合”药对主要活性成分有槲皮素、柚皮素和豆甾醇;核心靶点包括3-羟基-3甲羟甲基戊二酰辅酶A还原酶(HMGCR)、转录因子-κB p65(RELA)、白细胞介素1B、过氧化物酶体增殖物激活受体α(PPARA)、核受体辅激活因子1(NCOA1)、过氧化物酶体增殖物激活受体γ(PPARG)、C-C基序趋化因子2(CCL2)、前列腺素内过氧化物含酶基因(PTGS2)、核受体辅激活因子2(NCOA2)、核受体亚家族1组成员2(NR1I2)、单细胞色素P450 1A1(CYP1A1);关键通路为肿瘤坏死因子信号通路。结论:运用网络药理学方法揭示了“土茯苓-百合”药对通过多成分、多靶点、多通路治疗痛风性关节炎的作用特点,为临床应用提供了依据,也为进一步开展动物实验及临床试验提示了方向。

Background:“Tufuling(Rhizoma Smilacis Glabrae)-Baihe(Bulbus Lilii)”couplet medicinals has been widely used in the treatment of gout and has achieved good efficacy,but the mechanism of its action is not clear.Objective:To study the molecular mechanism of Tufuling-Baihe couplet medicinals in the treatment of gout based on network pharmacology.Methods:Taking the oral bioavailability and drug-like properties as parameters,the main active ingredients and action targets of“Tufuling-Baihe”couplet medicinals were screened by TCMSP database.GeneCards,OMIM,TTD,PharmGkb and DrugBank databases were used to predict the related targets of gouty arthritis.The common target of Tufuling-Baihe couplet medicinals and gouty arthritis was obtained by Venn diagram.Cytoscape 3.9.0 software was used to plot the regulatory network of TCM medicine-ingredient-disease-target,and STRING database was used to construct and analyze the protein-protein interaction network.Finally,the gene ontology(GO)enrichment analysis and gene interaction(KEGG)pathway analysis were carried out using R language.Results:There were 20 active ingredients and 185 corresponding targets of Tufuling-Baihe couplet medicinals.There were 410 targets for gout disease.There were 38 potential joint targets.The main active ingredients of Tufuling-Baihe couplet medicinals included quercetin,naringenin and stigmasterol.Core target genes included HMGCR,RELA,IL1B,PPARA,NCOA1,PPARG,CCL2,PTGS2,NCOA2,NR1I2,CYP1A1.The critical path was TNF-αsignaling pathway.Conclusion:The effects of Tufuling-Baihe couplet medicinals in the treatment of gouty arthritis through multi-ingredient,multi-target and multi-pathway are revealed by network pharmacology,which provides the basis for clinical application and suggests the direction for further animal experiments and clinical trials.