title: Olive oil phenols inhibit human hepatic microsomal activity.
abstract: We have examined the inhibition of human hepatic microsomal androstenedione 6beta-hydroxylation and both reductive and oxidative 17beta-hydroxysteroid dehydrogenase (17beta-HSD) activity by complex phenols found in olive oil. Structurally similar compounds were also examined for comparison. Androstenedione 6beta-hydroxylase activity was inhibited by oleuropein glycoside, hydroxytyrosol and gallic acid. Oleuropein glycoside, hydroxytyrosol, gallic acid and dihydroxybenzoic acid also inhibited reductive 17beta-HSD activity. Oxidative 17beta-HSD activity was not inhibited by any of the compounds tested; however gallic acid stimulated activity by approximately 30%. Androstenedione 6beta-hydroxylase activity showed atypical kinetics. For oleuropein glycoside, hydroxytyrosol and gallic acid the apparent K(i) values were determined to be 80, 77 and 70 micromol/L, respectively. Analysis of structural features of inhibitory compounds established that a 3,4-dihydroxyphenyl ethanol structure was required for inhibition of androstenedione 6beta-hydroxylase for this group of compounds.
authors.affiliation: Center for Pharmaceutical Research, School of Pharmacy and Medical Sciences, University of South Australia, SA, 5000, Australia.
authors.forename: I
authors.initials: I
authors.lastname: Stupans
authors.forename: G
authors.initials: G
authors.lastname: Stretch
authors.forename: P
authors.initials: P
authors.lastname: Hayball
mesh_terms: D002478:Cells, Cultured; D065607:Cytochrome P-450 Enzyme Inhibitors; D006801:Humans; D006913:Hydroxysteroid Dehydrogenases / Q000037:antagonists & inhibitors*; D008862:Microsomes, Liver / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D000069463:Olive Oil; D010636:Phenols / Q000494:pharmacology*; D010938:Plant Oils; D013250:Steroid Hydroxylases / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
chemical_list: D065607:Cytochrome P-450 Enzyme Inhibitors; D000069463:Olive Oil; D010636:Phenols; D010938:Plant Oils; D006913:Hydroxysteroid Dehydrogenases; C035507:3(17)-hydroxysteroid dehydrogenase; D013250:Steroid Hydroxylases; C022657:steroid hormone 6-beta-hydroxylase