Premium
Investigation of the in Vitro Metabolism of Evodiamine: Characterization of Metabolites and Involved Cytochrome P450 Isoforms
Author(s) -
Sun HongZhi,
Fang ZhongZe,
Cao YunFeng,
Sun XiaoYu,
Hong Mo
Publication year - 2013
Publication title -
phytotherapy research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.019
H-Index - 129
eISSN - 1099-1573
pISSN - 0951-418X
DOI - 10.1002/ptr.4766
Subject(s) - evodiamine , pharmacology , metabolite , cyp3a4 , cytochrome p450 , drug metabolism , cyp1a2 , microsome , chemistry , glucuronidation , metabolism , alkaloid , biochemistry , drug , biology , in vitro , stereochemistry
Evodiamine is the main active alkaloid of Evodia rutaecarpa ( E. rutaecarpa ) and has been demonstrated to exhibit many pharmacological activities including vasorelaxation, uterotonic action, anoxia and control of body temperature. The present study focused on the metabolism of evodiamine. Human and phenobarbital‐induced rat liver microsomal incubation of evodiamine in the presence of NADPH resulted in the formation of five major metabolites (M‐1, M‐2, M‐3, M‐4, M‐5). Four metabolites (M‐1, M‐2, M‐3 and M‐5) were identified to mono‐hydroxylated evodiamine and one metabolite (M‐4) was identified to be N‐demethylated evodiamine. CYP3A4, CYP2C9 and CYP1A2 were identified to be the main CYP isoforms involved in the metabolism of evodiamine in human liver microsomes. Finding new metabolites can help us decipher novel substance basis of efficiency and toxicity. Elucidation of drug metabolizing enzymes will facilitate explaining the individual difference for response to the same drugs or herbs and the potential drug–drug interaction or herb–drug interaction. Taken together, these results are of significance for better understanding the pharmacokinetic behaviour of evodiamine and helpful for clinical application of evodiamine and E. rutaecarpa . Copyright © 2012 John Wiley & Sons, Ltd.