The impact of sesquiterpenes β-caryophyllene oxide and trans-nerolidol on xenobiotic-metabolizing enzymes in mice in vivo

Xenobiotica. 2018 Nov;48(11):1089-1097. doi: 10.1080/00498254.2017.1398359. Epub 2017 Nov 10.

Abstract

1. Sesquiterpenes, constituents of plant essential oil, are popular bioactive compounds due to the positive effect on human health, but their potential toxicity and possible herb-drug interactions are often omitted. In our in vivo study, we followed up the effect of p.o. administration of two sesquiterpenes β-caryophyllene oxide (CAO) and trans-nerolidol (NER) on various xenobiotic-metabolizing enzymes in mice liver and small intestine. 2. To spot the early effect of studied compounds, enzymatic activity and mRNA levels were assessed 6 and 24 h after single dose. 3. CAO and NER markedly increased cytochromes P450 (CYP2B, 3A, 2C) activity and mRNA levels in both tissues. Liver also showed elevated activity of aldo-ketoreductase 1C and carbonyl reductase after treatment. Contrary, sesquiterpenes decreased NAD(P)H:quinone oxidoreductase 1 activity in small intestine. Among conjugation enzymes, only liver sulfotransferase activity was increased by sesquiterpenes. 4. Our results document that single dose of sesquiterpenes modulate activities and expression of several xenobiotic-metabolizing enzymes.

Keywords: Cytochrome P450; drug-metabolizing enzyme; enzyme induction; terpenes.

MeSH terms

  • Aldehyde Reductase / metabolism
  • Animals
  • Cytochrome P-450 Enzyme System / genetics
  • Cytochrome P-450 Enzyme System / metabolism
  • Enzymes / metabolism*
  • Estradiol Dehydrogenases / metabolism
  • Gene Expression Regulation, Enzymologic / drug effects
  • Inactivation, Metabolic / drug effects*
  • Intestine, Small / drug effects
  • Intestine, Small / enzymology
  • Liver / drug effects
  • Liver / enzymology
  • Male
  • Mice, Inbred Strains
  • NAD(P)H Dehydrogenase (Quinone) / metabolism
  • Polycyclic Sesquiterpenes
  • Sesquiterpenes / pharmacology*
  • Sesquiterpenes / toxicity

Substances

  • Enzymes
  • Polycyclic Sesquiterpenes
  • Sesquiterpenes
  • Cytochrome P-450 Enzyme System
  • Akr1a1 protein, mouse
  • Aldehyde Reductase
  • AKR1C13 protein, mouse
  • Estradiol Dehydrogenases
  • NAD(P)H Dehydrogenase (Quinone)
  • Nqo1 protein, mouse
  • nerolidol
  • caryophyllene oxide