基于网络药理学探讨黄芪桂枝五物汤治疗产后身痛的作用机制

Discussion About the Mechanism of Astragalus and Cinnamon Twig Five Substances Decoction in the Treatment of Postpartum Body Pain Based on Network Pharmacology

目的:基于网络药理学探讨黄芪桂枝五物汤治疗产后身痛的作用机制,并用分子对接进行验证。方法:利用TCMSP数据库检索并筛选黄芪桂枝五物汤的有效成分及相应作用靶点,利用OMIM数据库检索产后身痛的疾病靶点。通过STRING数据库分别构建化合物靶点与疾病靶点的蛋白-蛋白相互作用(protein-protein interaction,PPI)网络,运用Cytoscape 3.7.1软件中Merge功能,将黄芪桂枝五物汤活性成分靶点的PPI网络与相关疾病靶点的PPI网络合并取交集获得药物潜在作用靶点,对所得靶点通过DAVID数据库进行基因本体功能(gene ontology,GO)分析和京都基因与基因百科全书通路(Kyoto encyclopedia of genes and genomes,KEGG)富集分析。分别在RCSB PDB数据库与pubchem数据库中检索关键靶点,利用PyMol 2.4.0和Auto Dock Tools软件处理后进行分子对接。结果:共获得槲皮素、β-谷甾醇等63个有效成分和229个药物作用靶点,与376个疾病靶点进行合并后共获得组织型纤溶酶原激活剂、干扰素调节因子1(interferon regulatory factor 1,IRF1)、纤溶酶原激活剂抑制剂1、氧化低密度脂蛋白受体1(oxidized low density lipoprotein receptor 1,OLR1)、载脂蛋白B-100(Apolipoprotein B-100,APOB)、中性粒细胞胞质溶胶因子1(neutrophil cytosol factor 1,NCF1)、核转录因子κB抑制剂alpha (Nuclear factor-kappa B inhibitor alpha,NFKBIA)等10个黄芪桂枝五物汤治疗产后身痛的潜在作用靶点。经过GO和KEGG富集分析,共得到23个基因功能和13条通路。分子对接显示,关键化合物成分与靶蛋白亲和力较好。结论:黄芪桂枝五物汤中的槲皮素、β-谷甾醇、山奈酚等化合物可能通过破骨细胞分化、趋化因子信号通路、HIF-1信号通路等,作用于信号转导和转录激活因子、转录因子p65、IRF1、NFKBIA等靶点以治疗产后身痛。

Objective:To explore the mechanism of Astragalus and Cinnamon Twig Five Substances Decoction in the treatment of postpartum body pain by network pharmacology,and to verify it by molecular docking.Methods:TCMSP database was used to search and screen the effective ingredients and corresponding targets of Astragalus and Cinnamon Twig Five Substances Decoction,and OMIM database was used to search the disease targets of postpartum body pain.The PPI networks of compound targets and disease targets were structured through STRING database.By using the Merge function in Cytoscape 3.7.1 software,the PPI networks of active component targets of Astragalus and Cinnamon Twig Five Substances Decoction and related disease targets were combined and intersected to obtain potential drug targets.The obtained targets were analyzed by GO analysis and KEGG enrichment analysis through DAVID database.The key targets were retrieved in RCSB PDB database and pubchem database respectively,and the molecular docking was carried out after being processed by PyMol 2.4.0 and Auto Dock Tools software.Results:A total of 63 active compounds such as quercetin,β-sitosterol,etc.and 229 drug targets were obtained.After having been combined with 376 disease targets,10 potential targets of Astragalus and Cinnamon Twig Five Substances Decoction for the treatment of postpartum body pain were obtained:tissue plasminogen activator,interferon regulatory factor 1(IRF1),plasminogen activator inhibitor 1,oxidized low density lipoprotein receptor 1(OLR1),apolipoprotein B-100(APOB) Neutrophil cytosol factor 1(NCF1),nuclear factor-kappa B inhibitor alpha(NFKBIA).After GO and KEGG enrichment analysis,a total of 23 gene functions and 13 pathways were obtained.Molecular docking showed that the key compounds had strong affinity and good binding force with the target protein.Conclusion:The contents of quercetin,β-sitosterol,kaempferol and other compounds in Astragalus and Cinnamon Twig Five Substances Decoction may act on STAT1,RELA,IRF1,NFKBIA and other targets to treat postpartum body pain through osteoclast differentiation,chemokine signaling pathway and HIF-1 signaling pathway,etc.