Modulatory effect of humulene, caryophyllene and caryophyllene oxide on selected biotransformation enzymes in human liver cells

1 ABSTRACT Charles University Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Bc. Veronika Trnčáková Supervisor: doc. PharmDr. Boušová Iva, Ph.D. Title of diploma thesis: Modulatory effect of humulene, caryophyllene and caryophyllene oxide on selected biotransformation enzymes in human liver cells Sesquiterpenes are substances of natural origin, produced mainly by higher plants. They are mainly found in food supplements and natural medicines. Large structural diversity is a feature of these substances. The anti-inflammatory, antiparasitic and anti-cancer effects were also reported. The aim of this diploma thesis was to investigate the effect of selected sesquiterpenes, α-humulene (HUM), β-caryophyllene (KAR) and β-caryophyllene oxide (CAO), on gene and protein expression of selected phase I drug-metabolizing enzymes, which were carbonyl reductase 1 (CBR1), aldo/keto reductase 1C (AKR1) and several cytochrome P450 isoforms, namely CYP3A4, CYP2B6 and CYP2C. The effect of sesquiterpenes on the gene and protein expression of enzymes was studied using precision-cut human liver slices (8 mm diameter, 150-180 µm thickness). Liver samples were received from hepatic surgery of five subjects of both sexes and at 58-69 years of age. Liver slices were incubated with studied compounds (HUM, KAR,..