In Vitro Metabolism of Artepillin C by Rat and Human Liver Microsomes

Abstract

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 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 intrinsic clearance for Artepillin C was 16.63 ± 1.52 µL/min/mg protein. The 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.

Effects of Propolis Extract and Propolis-Derived Compounds on Obesity and Diabetes: Knowledge from Cellular and Animal Models

“…Of the cytochromes P450 (CYPs), which are the main enzymes involved in metabolizing chemical compounds, CYP1A, 2C, 2D, and 3A have different catalytic activities in different mammalian species, such as humans, mice, and rats [39]. Given that CYP1A and CYP2C contribute to the metabolism of dietary flavonoids and polyphenols [40,41], the kinetics of propolis-derived compounds in animal models are likely to be different from those in humans. Similarly, interspecies differences in intestinal microbiomes have been exhibited between mice and humans, and these differences severely affect the various metabolic profiles of polyphenols [38].…”

Artepillin C as an outstanding phenolic compound of Brazilian green propolis for disease treatment: A review on pharmacological aspects

“…In vitro metabolism of Art-C was investigated by measuring enzymatic kinetic parameters in rat liver microsomes and human liver microsomes by Carrão et al (2017). Two new metabolites of Art-C have been reported in both models and the chemical structures of metabolites formed by rat liver microsomes were elucidated by mass spectrometry.…”

Electrospray ionization tandem mass spectrometry of monoketone curcuminoids

“…Over the last decade, electrospray ionization tandem mass spectrometry (ESI‐MS/MS) has been used to identify natural and synthetic organic compounds mainly in combination with liquid chromatography (LC/MS/MS). Because MS is highly sensitive, it has been widely employed in in vitro and in vivo metabolism studies . In this context, the MS/MS data of the class of compounds under study play a key role .…”