补肾益精法调控AhR通路治疗硬皮病的机制:基于网络药理学及分子对接

Study on the mechanisms by which Bushen Yijing Decoction regulates AhR pathway in the treatment of scleroderma:Based on network pharmacology and molecular docking

目的通过网络药理学方法、分子对接方法分析芳香烃受体(AhR)信号通路在补肾益精法治疗硬皮病中的作用及其机制。方法通过TCMSP等数据库及LC-MS分析结果获取补肾益精法中药复方的有效活性成分及其靶点基因、AhR信号通路基因和硬皮病疾病基因,构建补肾益精法活性成分-AhR信号通路-硬皮病交集靶点网络图;使用STRING数据库构建蛋白互作网络;进行GO、KEGG富集分析;最后通过分子对接验证有效活性成分与AhR结合能力。结果阿魏酸、槲皮素、山奈酚、异阿魏酸、木犀草素在补肾益精法靶向AhR信号通路治疗硬皮病中发挥关键作用;其机制可能与调控参与硬皮病发病机制的IL-6、CTNNB1、HSP90AA1、TNF、PTGS2等AhR信号通路分子有关;分子对接显示阿魏酸、山奈酚、槲皮素、异阿魏酸、木犀草素等活性成分与AhR结合能均低于-6.0 kcal/mol,具有较好结合活性。结论补肾益精法治疗硬皮病的机制可能与阿魏酸、槲皮素、山奈酚、异阿魏酸、木犀草素等多种关键活性成分,靶向AhR信号通路,调控IL-6、CTNNB1、HSP90AA1、TNF、PTGS2等核心靶点相关。

Objective To analyze the effects and molecular mechanisms of AhR signaling pathway in the treatment of scleroderma with Bushen Yijing Decoction.Methods The active ingredients of Bushen Yijing Decoction and its target genes,AhR signaling pathway genes and the genes related to scleroderma were searched through TCMSP and other databases,and LC-MS results.Target gene network diagram of scleroderma,AhR pathway and the key active ingredients in Bushen Yijing Decoction were constructed.The protein-protein interaction network was constructed with STRING database,and GO and Genome KEGG were also performed.Finally,the molecular docking of the active ingredients and AhR were verified.Results Ferulic acid,quercetin,kaempferol,isoferulic acid and luteolin were key active ingredients in Bushen Yijing Decoction for the treatment of scleroderma by targeting AhR signaling pathway.These active ingredients possibly regulated AhR signaling pathway molecules,including IL-6,CTNNB1,HSP90AA1,TNF and PTGS2,which were involved in the pathogenesis of scleroderma.Molecular docking showed that the binding energies of ferulic acid,kaempferol,quercetin,isoferulic acid and luteolin with AhR were lower than-6.0 kcal/mol,indicating a good binding activity.Conclusions The mechanisms by which Bushen Yijing Decoction treats scleroderma can be attributed to the active ingredients such as ferulic acid,quercetin,kaempferol,isoferulic acid,luteolin,which target AhR signaling pathway and regulate core targets,including IL-6,CTNNB1,HSP90AA1,TNF and PTGS2.