Assessment of Rat Hepatic Cytochrome P450 Induction and Inhibition Potential of Chlorogenic Acid

Abstract:

Chlorogenic acid is a widely used naturally occurring ester, known to possess antioxidant properties. Chlorogenic acid was assessed for its potential to induce or inhibit the activities of rat liver cytochrome P450 (CYP450). Chlorogenic acid was administered to rats at the dose of 50 mg per kg per day for 14 days, following which livers were excised for preparation of microsomes. For studying the enzyme induction potential of chlorogenic acid, ethoxy resorufin-O-deethylation, pentoxy resorufin-O-depentylation, tolbutamide hydroxylation, p-nitrophenol hydroxylation and testosterone 6â-hydroxylation activities were determined in the rat liver microsomes using positive and negative controls. Following treatment to rats with 50 mg/kg/day of chlorogenic acid for 14 days no induction of any of the CYP activities was observed. CYP inhibition potential of chlorogenic acid was studied in rat liver microsomes at 0, 0.01, 0.03, 0.1, 0.3, 1, 3, 10, 30, 100, and 300 μM concentrations using the above mentioned assays. Chlorogenic acid showed no significant inhibition of any of CYP450 activities and the calculated IC was more than 50 300 μM. The study suggests that chlorogenic acid may have a very low drug-drug interaction potential.

Keywords: Chlorogenic acid, drug-drug interaction, CYP induction, CYP inhibition.