Effect of Crocetin on Cytochrome P450 Isoforms In Vitro

Abstract

. The activity of CYP450s was evaluated in pooled human liver microsomes (HLMs) in the presence of crocetin with various concentrations. The inhibition characteristics were estimated by fitting with the
Lineweaver-Burk plots. Crocetin was found to significantly inhibit the activity of CYP3A4, 2C9, and 2E1 in a
dose-dependent manner with the IC50 values of 18.04, 12.71, and 8.53 μM, respectively. The non-competitive
manner was observed in the inhibition of CYP3A4 with the Ki
value of 9.89 μM, while the inhibition of CYP2C9 and 2E1 was performed competitively with Ki
values of 6.13 and 4.22 μM, respectively. Interestingly, a
time-dependent manner was found during the inhibitory effect of crocetin on CYP3A4 activity. The KI
value
was 3.20 μM-1 and the Kinact value was 0.040 min-1. The obtained results demonstrated the inhibitory effect of
crocetin on the activity of CYP3A4, 2C9, and 2E1, which implies the potential of crocetin to interact with
co-administrated drugs and provides guidance for its clinical application.