Inactivation of cytochrome P450 by the food-derived complex phenol oleuropein

Complex phenols, such as the glycoside oleuropein and hydroxytyrosol, are found in high concentrations in the typical components of the Mediterranean diet. We have previously reported that oleuropein inhibits androstenedione 6β-hydroxylase activity, a CYP3A marker in human liver microsomes (Stupans, I., Stretch, G., Hayball, P., 2000. Olive oil phenols inhibit human hepatic microsomal activity. Journal of Nutrition. 130 2367–2370). Oleuropein, but not the structurally similar compounds hydroxytyrosol and secologanin, was found to be a mechanism-based inhibitor of androstenedione 6β-hydroxylase activity. Preincubation with 100 μ m oleuropein and NADPH resulted in a significantly lower androstenedione 6β-hydroxylase activity when compared to preincubation carried out with oleuropein without NADPH, 0.11±0.01 nmol/mg microsomal protein/min compared with 0.29±0.03 nmol/mg microsomal protein/min ( P