Effects of Cinnamophilin on Mouse Hepatic Drug-metabolizing Enzymes in Vitro and in Vivo

Cinnamophilin (CIN) showed protective effect against oxidative damage. Cytochrome P450-dependent monooxygenase (P450) and glutathione S-transferase (GST) are important drug-metabolizing enzymes and P450 plays an important role in drug-drug interactions. To assess the possible drug interactions, effects of CIN on mouse P450 and GST were studied. In vitro, CIN inhibited liver microsomal nifedipine oxidation activity with an IC50 of 17.3 ± 1.8 μM. However, CIN had no effect on 7-ethoxyresorufin O-deethylation and coumarin hydroxylation activities. In vivo, oral administration of CIN had no effects on liver microsomal P450 content and NADPH-P450 reductase activity. Hepatic P450-catalyzed oxidations of 7-ethoxyresorufin, 7-methoxyres-orufin, coumarin, tolbutamide, N-nitrosodimethylamine, and nifedipine were not affected by CIN. These results revealed that CIN was a mouse CYP3A inhibitor in vitro without affecting P450 and GST activities in vivo.