Geraniol Pharmacokinetics, Bioavailability and Its Multiple Effects on the Liver Antioxidant and Xenobiotic-Metabolizing Enzymes

Abstract

Geraniol is a natural monoterpene showing anti-inflammatory, antioxidant, neuroprotective and anticancer effects. No pharmacokinetic and bioavailability data on geraniol are currently available. We therefore performed a systematic study to identify the permeation properties of geraniol across intestinal cells, and its pharmacokinetics and bioavailability after intravenous and oral administration to rats. In addition, we systematically investigated the potential hepatotoxic effects of high doses of geraniol on hepatic phase I, phase II and antioxidant enzymatic activities and undertook a hematochemical analysis on mice. Permeation studies performed via HPLC evidenced geraniol permeability coefficients across an in vitro model of the human intestinal wall for apical to basolateral and basolateral to apical transport of 13.10 ± 2.3 × 10-3 and 2.1 ± 0.1⋅× 10-3 cm/min, respectively. After intravenous administration of geraniol to rats (50 mg/kg), its concentration in whole blood (detected via HPLC) decreased following an apparent pseudo-first order kinetics with a half-life of 12.5 ± 1.5 min. The absolute bioavailability values of oral formulations (50 mg/kg) of emulsified geraniol or fiber-adsorbed geraniol were 92 and 16%, respectively. Following emulsified oral administration, geraniol amounts in the cerebrospinal fluid of rats ranged between 0.72 ± 0.08 μg/mL and 2.6 ± 0.2 μg/mL within 60 min. Mice treated with 120 mg/kg of geraniol for 4 weeks showed increased anti-oxidative defenses with no signs of liver toxicity. CYP450 enzyme activities appeared only slightly affected by the high dosage of geraniol.

Chemical composition, antioxidant, anti-inflammatory and antiproliferative activities of the essential oil of Cymbopogon nardus, a plant used in traditional medicine

“…Other studies showed that the EO from C. nardus has antioxidant activity [22], which could be explained by its high content of monoterpene alcohol (40.77%). Indeed, geraniol [40] is a significant monoterpene in the EO we studied. Compared to gallic acid used as standard, it should be noted that the activity of the EO from C. nardus is however, lower.…”

Anti-arthritic activity of D-carvone against complete Freund’s adjuvant-induced arthritis in rats through modulation of inflammatory cytokines

“…Hence, in order to achieve required therapeutic effect, the oral dosage of D-carvone needs to be optimized. Monoterpenes are reported to have high bioavailability upon oral administration in rats [ 26 , 27 ]. Being a monoterpene, D-carvone is also presumed to have high bioavailability after oral administration.…”

Use of human liver and EpiSkin™ S9 subcellular fractions as a screening assays to compare the in vitro hepatic and dermal metabolism of 47 cosmetics‐relevant chemicals

“…however, it is reported to be metabolized by other pathways (Pavan et al, 2018). GSH conjugation of geraniol appears to be a minor metabolite, as the half-life in liver S9 was >240 min.…”

“…The main metabolite of nitrobenzene reported to be excreted in the urine is 4‐nitrophenol, which was not detected in the S9 incubations, possibly due to the analytical conditions but also due to the low turnover of this chemical (half‐life >240 min) and the reported high protein binding of nitrobenzene metabolites (IARC, ). Geraniol was conjugated to GSH in both liver and EpiSkin S9; however, it is reported to be metabolized by other pathways (Pavan et al, ). GSH conjugation of geraniol appears to be a minor metabolite, as the half‐life in liver S9 was >240 min.…”