基于多成分药物代谢的枸杞子质控成分遴选研究

Selection of Quality Control Components from Fructus Lycii Based on Multicomponent Metabolism

目的:基于多成分序贯代谢的研究策略,探讨枸杞子在体内的代谢成分,遴选枸杞子的质控成分。方法:制备枸杞子水提液后,运用在体双向肠灌流技术和灌胃采血技术收集其肠代谢、肝代谢及综合代谢样品,结合超高效液相色谱-四级杆/静电场高分辨质谱联用技术(UPLC-Q-Exactive MS),对枸杞子水提物、肠代谢样品、肝代谢样品及综合代谢样品中的成分进行鉴别,遴选枸杞子的质控成分。结果:枸杞子提取物经LC-MS分析,共鉴定出36个化学成分。序贯代谢研究表明,枸杞子中有20个原形入血成分,其中有17个成分在经过肠代谢后可以检测到,16个成分在经过肝代谢后可以检测到,11个成分经过灌胃给药后,在腹主动脉血中可以检测到。结论:根据序贯代谢的研究结果,可以将这11个成分作为枸杞子药材的候选指标性成分,其分别为咖啡酸己糖偶联物、香豆酸己糖偶联物、N-caffeoyl,N′-dihydrocaffeoyl spermidine dihexose、绿原酸、N1,N10-bis(dihydrocaffeoyl)spermidine hexose、香豆素、槲皮素-O-芸香糖苷、阿魏酸、芦丁、N-乙酰色氨酸、水杨酸。

Objective:In order to select the quality control components,and explore the metabolic components of Fructus Lycii in vivo,based on the research strategy of multicomponent sequential metabolism.Methods:After preparing the water extract of Fructus Lycii,in-vivo two-way intestinal perfusion technology and intragastric blood collection technology were used to collect its intestinal metabolism,liver metabolism and comprehensive metabolism samples,combined with ultra-high performance liquid chromatography-quadrupole/electrostatic field high-resolution mass spectrometry Technology(UPLC-Q-Exactive MS),to identify the ingredients in the water extract of wolfberry,intestinal metabolism samples,liver metabolism samples and comprehensive metabolism samples,and select the quality control components of Fructus Lycii.Results:A total of 36 chemical components were identified by LC-MS analysis of Fructus Lycii extract.Sequential metabolic studies have shown that there were 20 protoplasmic components in Fructus Lycii,of which 17 components could be detected after intestinal metabolism,16 components could be detected after intestinal metabolism followed by liver metabolism,and 11 components could be detected in comprehensive metabolic samples after intragastric administration.Conclusion:According to the results of sequential metabolism,these 11 elements can be used as quality control components of Fructus Lycii,including caffeic acid hexose conjugate,coumaric acid hexose conjugate,N-caffeoyl,N′-dihydrocaffeoyl spermidine dihexose,chlorogenic acid,N1,N10-bis(dihydrocaffeoyl)spermidine hexose,coumarin,quercetin 3-O-rutinoside,ferulic acid,rutin,N-acetyltryptophan,andsalicylic acid.