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灌胃和静脉注射甘草素后在大鼠血浆、尿液、胆汁和粪便中的代谢产物分析。

Metabolic Profiling of Glabridin in Rat Plasma, Urine, Bile, and Feces After Intragastric and Intravenous Administration.

机构信息

School of Pharmaceutical Sciences, Wenzhou Medical University, Chashan Higher Education Campus, Wenzhou, 325035, Zhejiang, China.

Medical School, Zhejiang University City College, Hangzhou, 310015, Zhejiang, China.

出版信息

Eur J Drug Metab Pharmacokinet. 2022 Nov;47(6):879-887. doi: 10.1007/s13318-022-00797-2. Epub 2022 Sep 15.

Abstract

BACKGROUND AND OBJECTIVES

Glabridin is usually used to treat cardiovascular and central nervous system diseases, which is a main bioactive phytoconstituent of licorice root. In this study, our aim was to obtain metabolic profiles of glabridin in rat plasma, urine, bile, and feces after intragastric and intravenous administration.

METHODS

By UPLC-QTOF-MS, the metabolites of glabridin were systematically analyzed and identified. An ACQUITY UPLC HSS T3 column (100 × 2.1 mm, 1.8 mm) and the mobile phase containing water with 0.1% formic acid (A) and acetonitrile with 0.1% formic acid (B) via gradient elution was used as the chromatographic condition for separation. An extracted ion chromatogram strategy with multiple prototype/metabolite intermediate templates and 71 typical metabolic reactions was suggested to completely profile the metabolites of glabridin.

RESULTS

For the first time, 13 compounds in total were recognized from urine, plasma, bile, and feces of rats with the metabolite profiling strategy. The main metabolic form of glabridin in rats consisted of the prototype, hydroxylation, glucuronide conjugation, decarbonylation, and tert-butyl to alcohol metabolites.

CONCLUSIONS

The results not only indicated a comprehensive study on the probable metabolic pathways of glabridin in vivo, but also provided useful data and information for future pharmacological studies of glabridin.

摘要

背景与目的

甘草素通常用于治疗心血管和中枢神经系统疾病,是甘草根中的主要生物活性植物成分。本研究旨在通过灌胃和静脉注射后,在大鼠血浆、尿液、胆汁和粪便中获得甘草素的代谢谱。

方法

通过 UPLC-QTOF-MS 系统地分析和鉴定甘草素的代谢产物。采用 ACQUITY UPLC HSS T3 柱(100×2.1mm,1.8mm)和包含 0.1%甲酸的水(A)和含 0.1%甲酸的乙腈(B)的梯度洗脱作为色谱分离条件。采用多原型/代谢物中间模板和 71 种典型代谢反应的提取离子色谱图策略,全面分析甘草素的代谢产物。

结果

首次采用代谢产物谱分析策略,从大鼠尿液、血浆、胆汁和粪便中共鉴定出 13 种化合物。甘草素在大鼠体内的主要代谢形式包括原型、羟化、葡萄糖醛酸结合、脱羧和叔丁基到醇代谢物。

结论

研究结果不仅表明了对甘草素体内可能代谢途径的全面研究,还为未来甘草素的药理学研究提供了有用的数据和信息。

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