Metabolism of isorhynchophylline in rats detected by LC-MS.
OBJECTIVE
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.
Wang
Wei
W
Division of Metabolic Engineering, Institute of Natural Medicine, University of Toyama, Toyama, Japan.
Ma
Chao-Mei
CM
Hattori
Masao
M
D000284:Administration, Oral; D000818:Animals; D002853:Chromatography, Liquid / Q000379:methods*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D020719:Glucuronides / Q000378:metabolism; D006900:Hydroxylation; D026121:Indole Alkaloids / Q000302:isolation & purification / Q000378:metabolism / Q000493:pharmacokinetics*; D008297:Male; D013058:Mass Spectrometry / Q000379:methods*; D008516:Medicine, Chinese Traditional; D000078183:Oxindoles; D051381:Rats; D017208:Rats, Wistar; D032070:Uncaria / Q000737:chemistry*
D020719:Glucuronides; D026121:Indole Alkaloids; D000078183:Oxindoles; C052714:rhyncophylline; D003577:Cytochrome P-450 Enzyme System