title: Metabolic pathway profiling of the derivative of important herbal component noscapine.
abstract: The present study aims to investigate the influence of metabolic behavior by the introduction of bromo atom into the structure of noscapine. Oral gavage of 50 mg/kg bromo-noscapine for 6- to 8-week-old male mice with C57BL/6 background resulted in the detection of the metabolite undergoing cleavage of methylenedioxy group (II), demethylated bromo-noscapine (III, IV), meconine (V), bromo-cotarnine (VI), bisdemethylated bromo-noscapine (VII), and their corresponding glucuronides (G1-G4) in urine, feces, and serum (24 h). In vitro human liver microsomes or mice liver microsomes incubation system can also give the formation of phase I metabolites. Furthermore, the phase I drug-metabolizing enzymes involved in the metabolism of bromo-noscapine was screened. Many CYP isoforms were involved in the formation of metabolite II, and CYP3A4, CYP1A1, CYP2C19, and CYP2D6 were major CYP isoforms. All the determined CYP isoforms showed the catalytic activity towards the formation of metabolites III, V, and VI. The major CYP isoforms involved in the catalytic formation of metabolite IV were CYP2C19, CYP2D6, and CYP2E1. In conclusion, to date, many structural derivatives of noscapine have been synthesized based on the efficiency. However, the metabolic behavior remains to be elucidated, and the present study gave an example through the investigation of metabolic pathway of bromo-noscapine. The introduction of bromo atom into the structure of noscapine did not alter the metabolites profile, but changed the drug-metabolizing enzyme profiles.
authors.affiliation: Department of Hematology-Oncology, ShiDong Hospital, 999 ShiGuang Road, Yangpu District, Shanghai, 200438, People's Republic of China.
authors.forename: Yonghua
authors.initials: Y
authors.lastname: Yao
authors.affiliation: School of Pharmacy, Zhejiang Chinese Medical University, No. 548, Binwen Road, Binjiang District, Hangzhou, 310053, Zhejiang, People's Republic of China. h87y7dw@126.com.
authors.forename: Yang
authors.initials: Y
authors.lastname: Xiong
mesh_terms: D000818:Animals; D006801:Humans; D008297:Male; D053858:Metabolic Networks and Pathways / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism; D009665:Noscapine / Q000008:administration & dosage / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D009665:Noscapine
keywords: Bromo-noscapine; Cytochrome P450; Metabolic pathway; Phase I