基于UPLC-Q-TOF-MS/MS的芍药甘草汤肝组织分布研究  

Study on liver tissue distribution of Shaoyao Gancao Decoction based on UPLCQ-TOF-MS/MS

作　　者：展佳琪 任逸飞 付雨萱 李爽 刘佳琦 刘姿雨 乔雪龙 牛丽颖 吴玲芳 ZHAN Jiaqi;REN Yifei;FU Yuxuan;LI Shuang;LIU Jiaqi;LIU Ziyu;QIAO Xuelong;NIU Liying;WU Lingfang(Hebei University of Traditional Chinese Medicine,Shijiazhuang 050091,China;Quality Evaluation&Standardization Engineering Research Center of Traditional Chinese Medicine,Shijiazhuang 050091,China;Hebei Traditional Chinese Medicine Formula Granule Engineering&Technology Innovate Center,Shijiazhuang 050091,China)

机构地区：[1]河北中医药大学,河北石家庄050091 [2]河北省中药配方颗粒技术创新中心,河北石家庄050091 [3]中药材品质评价与标准化河北省工程研究中心,河北石家庄050091

出　　处：《药物评价研究》2025年第2期462-476,共15页Drug Evaluation Research

基　　金：河北省自然科学基金资助项目(H2023423005);河北省中医药管理局科研计划项目(2023114,2020130);河北中医学院优秀青年基金项目(YQ2020006)。

摘　　要：目的研究大鼠ig芍药甘草汤后肝组织中的原型成分及代谢产物并分析其体内代谢途径。方法ig给予SD大鼠芍药甘草汤水煎液提取物0.4 g·kg^(-1)后,采集11个不同时间点大鼠肝组织样本。采用UPLC-Q-TOF-MS/MS技术对不同时间点的含药肝组织样本进行检测,使用Analyst®TF 1.7.1 Software初步处理质谱数据,再通过PeakView 2.0和Masterview1.0进行高级分析和可视化,获取原型成分及代谢产物的保留时间和质谱信息,结合MetabolitePilotTM1.5 Software的代谢产物分析识别功能解析不同时间点含药血清样品中的原型成分和代谢产物,总结其体内代谢规律。结果在负离子模式下,从大鼠肝组织共检测到71个原型成分,其中黄酮类成分35个,萜类成分19个,挥发油类成分9个,香豆素类成分5个,有机酸类成分2个及1个其他类成分。同时,检测到540个代谢产物。推测芍药甘草汤的主要化学成分在肝组织内的代谢途径主要包括苷键水解、酯水解、脱烃、氧化、还原、去甲基化、甲基化、葡萄糖醛酸化、硫酸酯化、甘氨酸化等。结论初步确定了芍药甘草汤在大鼠肝组织中的原型成分及代谢产物,并为进一步阐释芍药甘草汤的药效物质基础及作用机制提供参考依据。Objective To study the prototype components and metabolites in rat liver tissue after ig administration of Shaoyao Gancao Decoction and its metabolic pathways in vivo.Methods The liver tissue samples of SD rats were collected at 11 different time points after ig administration of the water decoction extract of Shaoyao Gancao Decoction(0.4 g∙kg^(-1)).An ultra-high performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry(UPLC-Q-TOF-MS/MS)technique was used to detect the drugcontaining liver tissue samples at different time points.Analyst®TF 1.7.1 Software was used to preliminarily process the mass spectrometry data,and then PeakView 2.0 and Masterview 1.0 were used for advanced analysis and visualization to obtain the retention time and mass spectrometry information of prototype components and metabolites.Combined with the metabolite analysis and recognition function of MetabolitePilotTM1.5 Software,the prototype components and metabolites in drug-containing serum samples at different time points were analyzed,and the metabolic rules in vivo were summarized.Results In the negative ion mode,a total of 71 prototype components were detected from rat liver tissue,including 35 flavonoids,19 terpenoids,9 volatile oils,5 coumarins,2 organic acids and 1 other component(protocatechuic aldehyde).At the same time,540 metabolites were detected.It is speculated that the metabolic pathways of the main chemical components of Shaoyao Gancao Decoction in liver tissue mainly include glycosidic bond hydrolysis,ester hydrolysis,dealkylation,oxidation,reduction,demethylation,methylation,glucuronidation,sulfation,and glycine.Conclusion The prototype components and metabolites of Shaoyao Gancao Decoction in rat liver tissue were preliminarily determined,it provided a reference for further explaining the pharmacodynamic material basis and mechanism of Shaoyao Gancao Decoction.

关 键 词：芍药甘草汤 UPLC-Q-TOF-MS/MS 肝组织 原型成分 代谢产物 

分 类 号：R284.1[医药卫生—中药学]