Nerolidol and Farnesol Inhibit Some Cytochrome P450 Activities but Did Not Affect Other Xenobiotic-Metabolizing Enzymes in Rat and Human Hepatic Subcellular Fractions.

Alena Špičáková,Diana Dimunová,Kristýna Krasulová,Vladimír Kubíček,Pavel Anzenbacher,Lenka Skálová,Barbora Szotáková,Martin Ambrož,Kateřina Lněničková,Zuzana Myslivečková

doi:10.3390/molecules22040509

Abstract

Sesquiterpenes, 15-carbon compounds formed from three isoprenoid units, are the main components of plant essential oils. Sesquiterpenes occur in human food, but they are principally taken as components of many folk medicines and dietary supplements. The aim of our study was to test and compare the potential inhibitory effect of acyclic sesquiterpenes, trans-nerolidol, cis-nerolidol and farnesol, on the activities of the main xenobiotic-metabolizing enzymes in rat and human liver in vitro. Rat and human subcellular fractions, relatively specific substrates, corresponding coenzymes and HPLC, spectrophotometric or spectrofluorometric analysis of product formation were used. The results showed significant inhibition of cytochromes P450 (namely CYP1A, CYP2B and CYP3A subfamilies) activities by all tested sesquiterpenes in rat as well as in human hepatic microsomes. On the other hand, all tested sesquiterpenes did not significantly affect the activities of carbonyl-reducing enzymes and conjugation enzymes. The results indicate that acyclic sesquiterpenes might affect CYP1A, CYP2B and CYP3A mediated metabolism of concurrently administered drugs and other xenobiotics. The possible drug–sesquiterpene interactions should be verified in in vivo experiments.

Highlights

Sesquiterpenes, defined as 15-carbon compounds formed from three isoprenoid units, are an extremely diverse, heterogeneous and large group of natural compounds
Inhibitory effects of acyclic sesquiterpenes cis-nerolidol (CNER), trans-nerolidol (TNER), and farnesol (FAR), which are commonly found in the human diet, on cytosolic and microsomal biotransformation enzymes, were tested in human and rat liver subcellular fractions
The inhibitory effect of sesquiterpenes at final concentrations of 100 μM on the main hepatic biotransformation enzymes was assessed by measuring enzyme activities towards specific substrates

Summary

Introduction

Sesquiterpenes, defined as 15-carbon compounds formed from three isoprenoid units, are an extremely diverse, heterogeneous and large group of natural compounds. Sesquiterpenes, together with monoterpenes, represent the major components of plant essential oils, widely used in folk medicines, health-supporting preparations and cosmetics [1]. Sesquiterpene structures form several acyclic, mono-, bi-, tri-, and tetracyclic systems. The acyclic representatives, called farnesans, are derived directly from the basic structure, farnesol (FAR). In,among amongothers, others,cabreuva, cabreuva, ambrette, jasmine, ylang, essential oils. Jasmine, ylang, and and rose rose essential oils.

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