Inhibitory effects of cornuside on human liver cytochrome P450 enzymes

Cornuside is an iridoid glycoside isolated from the fruits of Cornus officinalis Sieb. et Zucc. with antiallergic and hypoglycemic properties. This study aimed to investigate the interaction of cornuside with cytochrome P450 (CYP) enzymes which may provide a reference for the clinical application of Cornus officinalis. The impact of cornuside on CYP enzyme activity in human liver microsomes (HLMs) was examined in the presence of 0, 2.5, 5, 10, 25, 50, and 100 µM of cornuside. In order to estimate the inhibition properties, Lineweaver-Burk plots were plotted and kinetic parameters were obtained. Furthermore, the time-dependent inhibition of CYP3A4 activity by cornuside was also assessed. The activity of CYP3A4, 2C19, and 2E1 was suppressed by cornuside, with half-maximal inhibitory concentration (IC₅₀) values of 13.80, 19.44, and 24.55 µM, respectively. Furthermore, the inhibitory effect of cornuside was found to be non-competitive (K_i = 7.13 µM) and time-dependent (K_I = 7.19 µM, K_inact = 0.042 min^-1), whereas the inhibitory effect on CYP2C19 and 2E1 was found to be competitive, with K_i values of 9.92 µM and 12.38 µM, respectively. In vitro studies revealed that cornuside inhibited CYP3A4, 2C19, and 2E1. This indicates the possibility of drug-drug interaction between cornuside and drugs that are metabolized by these CYP enzymes when co-administered. These findings may provide a theoretical basis for clinical prescribing, particularly in the context of co-administration.