Inhibitory effect of quercetin-3-O-α-rhamnoside, p-coumaric acid, phloridzin and 4-O-β-glucopyranosyl-cis-coumaric acid on rats liver microsomes cytochrome P450 enzyme activities.

Abstract

P-coumaric acid, phloridzin, quercetin-3-O-α-rhamnoside and 4-O-β-glucopyranosyl-cis-coumaric acid isolated in Malus micromalus Makino fruit were investigated the inhibitory activity of cytochrome CYP450 enzyme by the probe test method of rat liver microsomes in vitro, and determined the role in drug metabolism and/or toxicology. Enzymatic kinetics method was used to determine the inhibition type of these components and corresponding inhibition constants. The results demonstrated that all the 4 compounds had no significance to inhibit the activities of CYP2E1 and CYP2C11. P-coumaric acid, phloridzin and quercetin-3-O-α-rhamnoside had a weak inhibitory effect on CYP3A4, which belonged to the competitive inhibitory type with inhibitory constants of 10.56, 30.79 and 40.29μmolL-1, respectively. 4-O-β-glucopyranosyl-cis-coumaric acid had a moderate inhibitory effect on CYP3A4, which belonged to the anti-competitive inhibition type and the inhibition constant was 5.56μmolL-1. The CYP1A2 could be weakly inhibited by p-coumaric acid in the competitive type, and the inhibition constant is 25.20μmolL-1 4-O-β-glucopyranosyl-cis-coumaric acid exhibited anti-competitive inhibition of CYP1A2 with an inhibition constant of 19.91μmolL-1, and the inhibition effect was weak. The results will be useful to optimize the clinical dosage regimen and avoid drug-drug interactions when it is utilized comminating with other medicines in the clinic.