【摘要】 目的 利用植物代谢组学结合网络药理学的方法,挖掘茅苍术和北苍术治疗溃疡性结肠炎(UC)的潜在活性成分,探究苍术治疗UC的作用机制。方法 基于超高液相色谱-四级杆飞行时间质谱联用(UPLC-Q-TOF/MS)技术结合OS 3.0软件鉴定苍术化学成分,利用非靶向植物代谢组学筛选茅苍术和北苍术的差异代谢物,通过TCMSP、HERB和SymMap等数据库的检索及文献补充,构建苍术的化学成分库,利用Swiss Target Prediction、GeneCards和DrugBank等数据库得到与疾病的共有靶点,并构建“成分-靶点”网络筛选网药活性成分。将2种共有靶点取并集,进行基因本体论(GO)和京都基因和基因组百科全书(KEGG)通路富集分析。通过蛋白互作网络(PPI)分析得到关键治疗靶点,构建“差异代谢物-关键治疗靶点-网药活性成分”网络。最后利用AutoDock4对活性成分和关键靶点进行分子对接验证。结果 从苍术中鉴定出197个化合物,两种苍术的27个差异代谢物与15个网药活性成分共有290个靶点。KEGG富集分析主要包括PI3K-Akt信号通路、MAPK信号通路和HIF-1信号通路等,蛋白互作网络分析得到信号传导转录激活因子3(STAT3)、蛋白激酶B(AKT1)和丝裂原活化蛋白激酶3(MAPK3)等17个关键靶点。分子对接结果显示活性成分和关键靶点展现出较强的结合能。结论 “差异代谢物-关键治疗靶点-网药活性成分”网络图表明绿原酸、白术内酯Ⅰ和汉黄芩素等是苍术治疗UC的潜在活性成分,主要通过调节肠道菌群、抑制炎症和抗氧化应激等多方面发挥治疗UC的作用,为临床合理用药提供科学依据。更多还原

【Abstract】 Objective To excavate the potential active ingredients of Atractylodes lancea(Thunb.)DC.and Atractylodes chinensis(DC.) Koidz.and explore the mechanism of action of Atractylodis Rhizoma for the treatment of ulcerative colitis(UC) using plant metabolomics combined with network pharmacology.Methods Based on UPLC-Q-TOF/MS technology combined with OS 3.0software to identify the chemical constituents of Atractylodis Rhizom,non-targeted plant metabolomics was used to screen the differential metabolites of Atractylodes lancea(Thunb.) DC.and Atractylodes chinensis(DC.) Koidz.The chemical constituents of Atractylodis Rhizom library of Atractylodis Rhizom was constructed by searching TCMSP,HERB and SymMap databases and literature supplementation.Using Swiss Target Prediction,GeneCards and DrugBank databases,the common targets of the diseases were obtained and a ’component-target’ network was constructed to screen the active ingredients of the net drug.The two shared targets were combined and analyzed by Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment.The key therapeutic targets were obtained by protein-protein interaction network(PPI) analysis,and the network of differential metabolite-key therapeutic target-net drug active ingredient was constructed.Finally,AutoDock4 was used to validate the molecular docking between the active ingredients and key targets.Results A total of 197 compounds were identified from Atractylodis Rhizoma,27 differential metabolites and 15 active ingredients have a total of 290 targets.KEGG analysis mainly included PI3K-Akt,MAPK,HIF-1 and other signaling pathways related to inflammation,and Protein-Protein Interaction analysis obtained 17 key targets such as STAT3,AKT1 and MAPK3.Molecular docking results showed that the active ingredients and key targets exhibited strong binding energy.Conclusions The network of differential metabolite-key therapeutic target-net drug active ingredient shows that Chlorogenic acid,Atractylenolide I,Wogonin and other compounds are potential active ingredients,mainly by regulating intestinal bacteria,inhibiting inflammation,and antioxidant stress in various aspects,providing scientific basis for rational clinical medication.更多还原