基于超高效液相色谱-四级杆-静电场轨道阱和网络药理学技术的清肝颗粒质量评价研究  

Quality Evaluation of Qinggan Granules Based on UPLC-Q-Exactive-Orbitrap-MS and Network Pharmacology

作　　者：王璟璐 关永霞 范建伟 李艳芳 张贵民 WANG Jinglu;GUAN Yongxia;FAN Jianwei;LI Yanfang;ZHANG Guimin(School of Traditional Chinese Medicine,Guangdong Pharmaceutical University,Guangzhou 510000,China;State Key Laboratory of Integration and Innovation of Classic Formula and Modern Chinese Medicine,Linyi 276000,China;Lunan Pharmaceutical Group Co.,Ltd.,Linyi 276006,China)

机构地区：[1]广东药科大学中药学院,广州510000 [2]经方与现代中药融合创新全国重点实验室,临沂276000 [3]鲁南制药集团股份有限公司,临沂276006

出　　处：《世界中医药》2024年第14期2035-2047,共13页World Chinese Medicine

基　　金：国家重点研发计划“中医药现代化”重点专项(2022YFC3502100);山东省重点研发计划项目(2021CXGC010508)。

摘　　要：目的:阐明清肝颗粒治疗黄疸性肝炎的物质基础,建立科学的质量控制方法。方法:采用超高效液相色谱-四级杆-静电场轨道阱(UPLC-Q-Exactive-Orbitrap-MS)技术对清肝颗粒的活性成分进行表征分析;以清肝颗粒中鉴定出的活性成分为目标对象,进行网络药理学和分子对接研析,并建立多成分含量测定方法。结果:共鉴定出134个成分,其中黄酮类50个、糖苷类8个、苯丙素类17个、三萜类11个、萜类6个、氨基酸类11个、有机酸类9个、脂肪酸类7个、生物碱类8个、挥发油类5个、醌类1个,并解析了黄酮类、萜类、有机酸类、生物碱类以及糖苷类代表性化合物的裂解规律。通过网络药理学分析筛选出8个核心靶点。预测了主要活性成分为异甘草素、腺苷、甘草素、鸟苷、4,5-二咖啡酰奎宁酸等。其次,依据可测性、特征性以及活性相关性的原则,建立了3,4-二咖啡酰奎宁酸、(R,S)-告依春、甘草素、4,5-二咖啡酰奎宁酸和甘草酸铵等5个潜在活性成分的含量测定方法。结论:筛选出了清肝颗粒治疗黄疸性肝炎的主要药效活性成分,并展开定量研究,可为清肝颗粒质量控制水平的提高提供了依据。Objective:To elucidate the material basis of Qinggan Granules in treating icteric hepatitis and establish a scientific quality control method.Methods:The active components of Qinggan Granules were characterized and analyzed using ultra-high-performance liquid chromatography-quadrupole-electrostatic field orbitrap mass spectrometry(UPLC-Q-Exactive-Orbitrap-MS).Network pharmacology and molecular docking were conducted with the identified active components as target objects,and a multi-component quantification method was established.Results:A total of 134 components were identified,including 50 flavonoids,8 glycosides,17 phenylpropanoids,11 triterpenoids,6 terpenoids,11 amino acids,9 organic acids,7 fatty acids,8 alkaloids,5 essential oils,and 1 quinone.The fragmentation patterns of representative compounds from flavonoids,terpenoids,organic acids,alkaloids,and glycosides were analyzed.Network pharmacology analysis identified 8 core targets,and the main active components were predicted to be isoglycyrrhizin,adenosine,glycyrrhizin,guanosine,and 4,5-dicaffeoylquinic acid.Based on measurability,characteristic features,and activity relevance,a quantification method for five potential active components,including 3,4-dicaffeoylquinic acid,(R,S)-goitrin,glycyrrhizin,4,5-dicaffeoylquinic acid,and ammonium glycyrrhizinate,was established.Conclusion:The main pharmacologically active components of Qinggan Granules in treating icteric hepatitis were identified and quantitatively studied,providing a basis for improving the quality control of Qinggan Granules.

关 键 词：清肝颗粒 超高效液相色谱-四级杆-静电场轨道阱 定性分析 裂解途径 网络药理学 分子对接 黄疸性肝炎 多成分含量测定 

分 类 号：R285[医药卫生—中药学]