白皮杉醇苷在大鼠体内外的葡萄糖醛酸结合代谢研究

doi:10.16333/j.1001-6880.2015.05.008

天然产物研究与开发 ›› 2015, Vol. 27 ›› Issue (5): 793-798.doi: 10.16333/j.1001-6880.2015.05.008

白皮杉醇苷在大鼠体内外的葡萄糖醛酸结合代谢研究

张靖悦，刘卉，郝盛源，李方悦，许卉*

烟台大学药学院，烟台264005

出版日期:2015-05-30 发布日期:2015-06-05

In vivo and in vitro Glucuronidation Metabolism of Piceatannol Glucopyranoside in Rat

ZHANG Jing-yue, LIU Hui, HAO Sheng-yuan, LI Fang-yue, XU Hui*

School of Pharmacy,Yantai University,Shandong Yantai 264005,China

Online:2015-05-30 Published:2015-06-05

摘要/Abstract

摘要： 白皮杉醇苷（PG）是藏边大黄中一种天然抗氧化剂，前期研究发现其极易发生代谢。本文主要研究PG在大鼠体内外的葡萄糖醛酸结合代谢特征。SD大鼠经尾静脉注射给予PG（20 mg/kg），采集给药后胆汁样品，采用LC-MS对主要代谢产物进行结构推测。在此基础上，研究大鼠肝微粒体体外温孵体系中PG的葡萄糖醛酸结合代谢，并测定酶促反应动力学参数。实验结果显示SD大鼠经尾静脉注射给予PG，可在胆汁中快速检测到多种PG及其衍生物的葡萄糖醛酸结合代谢产物。在大鼠肝微粒体体外温孵体系中，PG代谢生成两个与体内一致的单葡萄糖醛酸结合代谢物，其葡萄糖醛酸结合代谢的最大反应速率（V_max）、米氏常数（K_m）和肝内清除率CL_int（V_max/K_m）分别为10.11 nmol/(min·mg)、0.36 mmol/L和0.028 mL/(min·mg)。PG经静脉途径进入大鼠体内可经肝脏被快速地广泛代谢，葡萄糖醛酸结合代谢是其体内消除的主要途径之一。大鼠肝脏的葡萄糖醛酸转移酶对PG有较强的亲和力，可催化PG发生快速的葡萄糖醛酸结合代谢。

关键词: 白皮杉醇苷, 葡萄糖醛酸结合, 大鼠胆汁, 肝微粒体, 代谢动力学

Abstract: Piceatannol-4′-O-β-D-glucopyranoside (PG),a natural antioxidant abundant in Rheum emodi Wall,was found to be an easihy metabolized substrate.The present study was aimed to study glucuronidation of PG in rat in vivo and in vitro. Rat bile samples were collected after a single intravenous bolus injection of PG at dose of 20 mg/kg.The metabolic profiling was performed using LC-MS,and the principal glucuronide metabolites were deduced.Then in vitro glucuronidation was investigated in rat liver microsomes,and the kinetic properties were determined.The results showed that PG can be quickly metabolized to glucuronide metabolites after intravenous administration in rat.In the in vitro co-incubation system containing PG and rat liver microsomes,two main mono-glucuronide metabolites of PG were observed,and the metabolic profile was found to be similar to that in vivo. The maximum reaction rate (V_max) of glucuronidation was 10-11 nmol/(min·mg), Michaelis-Menten constant (K_m) was 0.36 mmol/L,and liver clearance (CL_int) was 0.028 mL/(min·mg),respectively.All the findings indicated that UGTs in rat liver have fairly high affinity with PG and were responsible for the rapid glucuronidation of PG,which was one of the main elimination pathways of PG in rat.

Key words: piceatannol-4&prime, -O-&beta, -D-glucopyranoside, glucuronidation, rat bile, liver microsomes, metabolic kinetics

中图分类号:

R285.5

张靖悦，刘卉，郝盛源，李方悦，许卉*. 白皮杉醇苷在大鼠体内外的葡萄糖醛酸结合代谢研究[J]. 天然产物研究与开发, 2015, 27(5): 793-798.

ZHANG Jing-yue, LIU Hui, HAO Sheng-yuan, LI Fang-yue, XU Hui*. In vivo and in vitro Glucuronidation Metabolism of Piceatannol Glucopyranoside in Rat[J]. NATURAL PRODUCT RESEARCH AND DEVELOPMENT, 2015, 27(5): 793-798.

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白皮杉醇苷在大鼠体内外的葡萄糖醛酸结合代谢研究

In vivo and in vitro Glucuronidation Metabolism of Piceatannol Glucopyranoside in Rat

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