目的 探究甘枣宁的主要活性成分，预测并验证其治疗非酒精性脂肪性肝病（non-alcoholic fatty liver disease，NAFLD）的主要物质基础。方法 采用超高效液相色谱-四级杆飞行时间串联质谱（UPLC-Q-TOF-MS/MS），明确甘枣宁水煎液的化学成分。采用网络药理学方法检索甘枣宁活性成分及其潜在靶点，将药物靶点与NAFLD相关靶点取交集，进行蛋白质与蛋白质相互作用（protein-protein interaction，PPI）、基因本体（gene ontology，GO）功能及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。考察甘枣宁水煎液及（S）-N-衡州乌药碱、（R）-N-衡州乌药碱、N-去甲基亚美罂粟碱、O-去甲基荷叶碱、（-）-表儿茶素和N-去甲基荷叶碱6个关键活性成分对小鼠单核巨噬细胞RAW264.7上清液一氧化氮水平的影响；考察甘枣宁水煎液及N-去甲基荷叶碱对RAW264.7细胞存活率的影响。结果 从甘枣宁水煎液鉴定出96个主峰成分，网络药理学分析出甘枣宁治疗NAFLD的活性成分31个，所对应的相关靶点42个，其中一氧化氮合酶3（nitric oxide synthase 3，NOS3）、白细胞介素-6（interleukin-6，IL-6）等靶点关联性较强；甘枣宁治疗NAFLD主要涉及糖尿病并发症中的晚期糖基化终末产物（advanced glycation end products，AGEs）及其糖基化终末产物受体（receptor for advanced glycation end products，RAGE）通路、程序性坏死等通路。甘枣宁水煎液具有良好的抗炎活性，N-去甲基荷叶碱可能为其发挥抗炎作用的关键成分。结论 甘枣宁治疗NAFLD具有多成分、多靶点的特点，其药效物质基础与抗炎相关。

Objective To explore the main active ingredients of Ganzaoning (甘枣宁), and predict and verify its main material basis for treatment of non-alcoholic fatty liver disease (NAFLD). Methods Ultra-high performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometer (UPLC-Q-TOF-MS/MS) was used to determine the chemical composition of Ganzaoning Decoction. Network pharmacology was used to search for active ingredients and potential targets of Ganzaoning, drug targets and NAFLD-related targets were taken the intersection, protein-protein interaction (PPI) and gene ontology (GO) function enrichment analysis and Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis were performed. The effect of Ganzaoning Decoction and (S)-N-coclaurine, (R)-N-coclaurine, N-desmethylame, O-nornuciferine, (-)-epicatechin, N-nornuciferine on NO levels in supernatant of RAW264.7 cells were investigated; Effect of Ganzaoning Decoction and N-nornuciferine on survival rate of RAW264.7 cells were investigated. Results A total of 96 main peak components were identified from Ganzaoning decoction, 31 active ingredients of Ganzaoning in treatment of NAFLD and 42 corresponding targets were identified by network pharmacology, nitric oxide synthase 3 (NOS3), interleukin-6 (IL-6) and other targets had a strong correlation. Ganzaoning in treatment of NAFLD mainly involved advanced glycation end products (AGEs) and its receptor for advanced glycation end products (RAGE) pathway, programmed necrosis and other pathways. Ganzaoning Decoction had a good anti-inflammatory activity, and N-nornuciferine may be a key component of its anti-inflammatory effect. Conclusion Ganzaoning has the characteristics of multiple components and multiple targets in the treatment of NAFLD, and its pharmacodynamic material basis is related to anti-inflammation.

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