In vitro metabolism of liquiritigenin in liver microsomes of different species / 中草药

ABSTRACT

Objective: To compare in vitro metabolic differences of liquiritigenin, an aglycone of liquiritin, among liver microsomes of different species, which would provide reference for further research and development of liquiritin. Methods: Metabolic stability and metabolic biotransformation were investigated after liquiritigenin was incubated with rat, mouse, human, dog, and monkey liver microsomes. Metabolic stability was evaluated using a substrate depletion approach, and the results were reported as "% liquiritigenin remaining", which was then used to calculate the in vitro half-life (t1/2). Metabolic biotransformation was characterized by metabolite profiling. Results: In liver microsomal incubation systems of five species, the t1/2 values of liquiritigenin for phase I were as follows rat < mouse < human < monkey < dog, whereas for phase II, the metabolic rates were all fast and the remaining of liquiritigenin were all below 50% in 5 min except mouse. In addition, phase II metabolite profiling in monkey liver microsomes was identical to that of human, but marked differences were found between other species and human. Conclusion: The metabolic characteristics of liquiritigenin in monkey liver microsomes is most similar to that of human, then followed by dog, and marked differences existed between rat, mouse and human. Therefore, monkey or dog could be the animal model for further preclinical pharmacokinetic and toxicological studies.