Pharmacokinetic characterization of carnosol from rosemary (Salvia Rosmarinus) in male C57BL/6 mice and inhibition profile in human cytochrome P450 enzymes

Toxicol Appl Pharmacol. 2021 Nov 15:431:115729. doi: 10.1016/j.taap.2021.115729. Epub 2021 Sep 27.

Abstract

Rosemary (Salvia Rosmarinus) is a rich source of dietary diterpenes with carnosol as one of the major polyphenols used to standardize rosemary extracts approved as a food preservative, however, at present there is not any information on the murine pharmacokinetic profile of carnosol or its potential for drug interactions. The present study utilizes cell-free, cell-based, and animal-based experiments to define the pharmacokinetic profile of the food based phytochemical carnosol. Mice were administered carnosol (100 mg/kg body weight) by oral gavage and plasma levels were analyzed by LC-MS/MS to establish a detailed pharmacokinetic profile. The maximum plasma concentration exceeded 1 μM after a single administration. The results are significant as they offer insights on the potential for food-drug interactions between carnosol from rosemary and active pharmaceutical ingredients. Carnosol was observed to inhibit selected CYP450 enzymes and modulate metabolic enzymes and transporters in in vitro assays.

Keywords: Carnosol; Diterpene; Food Preservative; Pharmacokinetics; Rosemary; Salvia Rosmarinus.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Abietanes / administration & dosage
  • Abietanes / blood
  • Abietanes / isolation & purification
  • Abietanes / pharmacokinetics*
  • Administration, Oral
  • Animals
  • Biological Availability
  • Cottonseed Oil / chemistry
  • Cytochrome P-450 Enzyme Inhibitors / administration & dosage
  • Cytochrome P-450 Enzyme Inhibitors / blood
  • Cytochrome P-450 Enzyme Inhibitors / isolation & purification
  • Cytochrome P-450 Enzyme Inhibitors / pharmacokinetics*
  • Cytochrome P-450 Enzyme System / metabolism*
  • Drug Stability
  • Food Preservatives / administration & dosage
  • Food Preservatives / isolation & purification
  • Food Preservatives / pharmacokinetics*
  • HT29 Cells
  • Hep G2 Cells
  • Humans
  • Isoenzymes
  • Male
  • Membrane Transport Proteins / drug effects
  • Membrane Transport Proteins / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Rosmarinus / chemistry
  • Temperature

Substances

  • Abietanes
  • Cottonseed Oil
  • Cytochrome P-450 Enzyme Inhibitors
  • Food Preservatives
  • Isoenzymes
  • Membrane Transport Proteins
  • carnosol
  • Cytochrome P-450 Enzyme System