基于HPLC-Q-TOF-MS和网络药理学探讨田基黄治疗急性胰腺炎的作用及其机制  

Effect and Mechanism of Hypericum japonicum on the Treatment of Acute Pancreatitis Based on HPLC-Q-TOF-MS and Network Pharmacology

作　　者：焦雪菲 丁林[1] JIAO Xuefei;DING Lin(College of Pharmacy,Jining Medical University,Rizhao 276826,China)

机构地区：[1]济宁医学院药学院,山东日照276826

出　　处：《中国药学杂志》2023年第22期2069-2078,共10页Chinese Pharmaceutical Journal

基　　金：国家自然科学基金项目资助(81772920);山东省自然科学基金面上项目资助(ZR2022MH176)。

摘　　要：目的本研究基于高效液相色谱/高分辨飞行时间质谱技术(HPLC-Q-TOF-MS)和网络药理学分析田基黄治疗急性胰腺炎物质基础。方法采用HPLC-Q-TOF-MS分析技术,通过精确质量数、二级质谱数据、质谱裂解规律以及天然产物分子网络数据库(GNPS)生成化学成分的分子网络,推测可能的化合物结构。利用网络药理学方法获得田基黄化学成分和急性胰腺炎疾病潜在相关靶点而后取交集,构建“化学成分-疾病-靶点”网络。采用STRING数据库构建蛋白相互作用网络,再通过Metascape数据库进行基因本体(Gene Ontology,GO)功能与京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)通路富集分析。通过构建牛磺胆酸诱导急性胰腺炎大鼠模型,测定血浆中淀粉酶(AMS)、脂肪酶(LPS)、丙二醛(MDA)、谷胱甘肽过氧化物酶(GSH+Px)、过氧化氢(H_(2)O_(2))及一氧化氮(NO)水平。结果从田基黄中共计鉴定42个化合物,筛选出槲皮素、香豆醇葡萄糖苷、龙胆苦苷等10个核心成分,作用于白蛋白(albumin,ALB)和碳酸酐酶Ⅱ重组蛋白(recombinant Carbonic AnhydraseⅡ,CA2)等51个靶点,参与调节缺氧诱导因子(HIF-1)信号通路。血清AMS、LPS、MDA、H_(2)O_(2)及NO均显著性降低(P<0.01),GSH-Px水平升高(P<0.05)。结论田基黄可能通过调控HIF-1信号通路减少体内氧化应激,并抑制炎症因子释放,发挥对急性胰腺炎的治疗作用。OBJECTIVE To analyze and identify the chemical components in Hypericum japonicum for treatment of acute pancreatitis based on HPLC-Q-TOF-MS and network pharmacology analysis,and explore the mechanism by network pharmacology,which was initially verified by rat model of acute pancreatitis.METHODS HPLC-Q-TOF-MS analysis technology was used,and the molecular network of chemical components was generated by accurate mass number,secondary mass spectrometry data,mass spectrometry cracking law and GNPS database to infer the possible compound structure.The chemical constituents of Hypericum japonicum and the potential related targets of acute pancreatitis were obtained by network pharmacology,and then the intersection was taken to construct a“chemical constituents-disease-target”network.The protein interaction network was constructed by STRING database,and then the GO function and KEGG pathway enrichment were analyzed by Metascape database.A rat model of acute pancreatitis induced by taurocholic acid was established.Amylase(AMS),lipase(LPS),malondialdehyde(MDA),glutathione peroxidase(GSH+Px),hydrogen peroxide(H_(2)O_(2))and nitric oxide(NO)levels were measured.RESULTS A total of 42 compounds were identified from Hypericum japonicum,and 10 core components such as quercetin,coumarol glucoside and gentiopicroside were screened out,which acted on 51 targets such as ALB and CA2 and participated in the regulation of HIF-1 signaling pathway.Serum AMS,LPS,MDA,H_(2)O_(2) and NO levels all decreased significantly(P<0.01),while GSH-Px level increased(P<0.05).CONCLUSION Hypericum japonicum may play a therapeutic role in acute pancreatitis by regulating hypoxia-inducible factor(HIF-1)signaling pathway to reduce oxidative stress in vivo and inhibit the release of inflammatory factors.

关 键 词：田基黄 急性胰腺炎 高效液相色谱-四级杆飞行时间质谱 网络药理学 

分 类 号：R966[医药卫生—药理学]