LC-MS 检测大鼠中异钩藤堿的代谢。
Metabolism of isorhynchophylline in rats detected by LC-MS.
机构信息
Division of Metabolic Engineering, Institute of Natural Medicine, University of Toyama, Toyama, Japan.
出版信息
J Pharm Pharm Sci. 2010;13(1):27-37. doi: 10.18433/j33g60.
PURPOSE
This paper investigates the metabolic fate of isorhynchophylline (ISOR) as a main bioactive oxindole alkaloid in the traditional Chinese medicine.
METHODS
After oral administration of ISOR to rats, plasma, bile, urine and feces were analyzed by LC-MS. Hydroxylation of ISOR and successive glucuronidation proceeded in vitro by incubation with rat liver microsomes.
RESULTS
ISOR was identified in plasma, 11-hydroxyisorhynchophylline 11-O--D-glucuronide (MI1) and 10-hydroxyisorhynchophylline 10-O--D-glucuronide (MI2) in bile, and free 11-hydroxyisorhynchophylline (MI3) and 10-hydroxyisorhynchophylline (MI4) in urine and feces. Within 24 h, 71.6% of ISOR was excreted into the feces (in 20.0 g) and 13.8% into the urine (in 20.0 ml) of rats after oral administration of 37.5 mg/kg. Monitoring by LC-MS showed that 8.5% of ISOR was metabolized to MI3 and MI4 in a ratio of ca. 1:1. Specific inhibition of CYP isozymes indicated that CYP2D, CYP1A1/2 and CYP2C participate in ISOR hydroxylation.
CONCLUSIONS
ISOR was involved in the circulatory system after oral administration. Cytochrome P450 (CYP) in rat liver microsomes played a key role in ISOR hydroxylation.
目的
本文研究了作为传统中药中主要生物活性吲哚生物碱的异钩藤碱（ISOR）的代谢途径。
方法
在大鼠口服 ISOR 后，通过 LC-MS 分析血浆、胆汁、尿液和粪便。通过与大鼠肝微粒体孵育，进行 ISOR 的羟化和连续的葡萄糖醛酸化。
结果
ISOR 在血浆中被鉴定出来，11-羟基异钩藤碱 11-O--D-葡萄糖醛酸苷（MI1）和 10-羟基异钩藤碱 10-O--D-葡萄糖醛酸苷（MI2）在胆汁中，游离的 11-羟基异钩藤碱（MI3）和 10-羟基异钩藤碱（MI4）在尿液和粪便中。在大鼠口服 37.5mg/kg 后 24 小时内，71.6%的 ISOR 以粪便（20.0g）的形式排泄，13.8%以尿液（20.0ml）的形式排泄。通过 LC-MS 监测表明，8.5%的 ISOR 在体内代谢为 MI3 和 MI4，比例约为 1:1。CYP 同工酶的特异性抑制表明 CYP2D、CYP1A1/2 和 CYP2C 参与了 ISOR 的羟化作用。
结论
ISOR 在口服给药后参与了循环系统。大鼠肝微粒体中的细胞色素 P450（CYP）在 ISOR 羟化中起着关键作用。
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