Species Difference of Asarinin Metabolism in vitro and its Effect on the Activity of Cytochrome P450 Enzymes

Abstract

Aim: To investigate the metabolic behaviors of asarinin in different species and found animal models with metabolic pathways similar to those in humans and to study the effect (inhibition or induction) between asarinin and cytochrome P450 enzymes (CYP450s). Materials and Methods: The interspecies difference in asarinin metabolism was studied using liver microsomes (LMs) from humans and six mammals including rabbits, mini pigs, dogs, monkeys, rats, and mice. The potential drug–drug interactions (DDIs) between asarinin and cytochrome P450 enzymes was studied by incubating with six CYP enzymes in human liver microsomes (HLMs). Results: The metabolic profiles revealed substantially different metabolism of asarinin among the seven species. Moreover, the potential DDIs between asarinin and cytochrome P450 enzymes were studied in vitro by incubating with six CYP enzymes in HLMs, it was found that asarinin inhibited CYP2C9, CYP3A4, and CYP2E1 activity. Conclusion: The interspecies comparison can help find other species that have similar metabolic pathways to humans. There were potential DDIs between asarinin and some drugs metabolized by CYP2C9, CYP2E1, and CYP3A4.