In Vitro Metabolism of Artepillin C by Rat and Human Liver Microsomes
Carregando...
Arquivos
Fonte externa
Fonte externa
Data
Orientador
Coorientador
Pós-graduação
Curso de graduação
Título da Revista
ISSN da Revista
Título de Volume
Editor
Tipo
Artigo
Direito de acesso
Acesso restrito
Arquivos
Fonte externa
Fonte externa
Resumo
Artepillin C, a natural product present in the Brazilian green propolis, has several biological properties. Among these properties, the antitumor action of this product is noteworthy and makes it a promising drug candidate for the treatment of several types of cancer. This paper describes the in vitro metabolism of Artepillin C in rat and human liver microsomes. The rat model suggested a sigmoidal profile for the metabolism, adapted to the Hill's kinetic model. The enzymatic kinetic parameters were as follows: maximal velocity = 0.757 ± 0.021 μmol/mg protein/min, Hill coefficient = 10.90 ± 2.80, and substrate concentration at which half-maximal velocity of a Hill enzyme is achieved = 33.35 ± 0.55 μM. Based on these results, the calculated in vitro intrinsic clearance for Artepillin C was 16.63 ± 1.52 μL/min/mg protein. The in vitro metabolism assay conducted on the human model did not fit any enzymatic kinetic model. Two novel metabolites were formed in both mammal microsomal models and their chemical structures were elucidated for the first time. The main human cytochrome P450 isoforms involved in Artepillin C metabolism had been identified, and the results suggest a majority contribution of CYP2E1 and CYP2C9 in the formation of the two metabolites.
Descrição
Palavras-chave
Artepillin C, enzymatic kinetics, in vitro metabolism, liver microsomes, natural product
Idioma
Inglês
Citação
Planta Medica, v. 83, n. 8, p. 737-745, 2017.
