title: The inhibition of bone resorption in rats treated with (-)-menthol is due to its metabolites.
abstract: (-)-Menthol, a monoterpene from Mentha species (Lamiaceae), has been shown to inhibit bone resorption in vivo by an unknown mechanism. In the present study, plasma and urine profiling in rats determined by GC/MS demonstrate that (-)-menthol is extensively metabolized, mainly by hydroxylation and carboxylation, and excreted in the urine, in part as glucuronides. In plasma, very low concentrations of (-)-menthol metabolites were detected after a single dose of (-)-menthol, whereas after repeated treatment, several times higher concentrations and long residence times were measured. In contrast, the elimination of unchanged (-)-menthol was increased by repeated treatment. (-)-Menthol, at concentrations found in plasma, did not inhibit bone resorption in cultured mouse calvaria (skull). However, the neutral metabolites of (-)-menthol, extracted from urine of rats fed with (-)-menthol, inhibited bone resorption in vitro, the concentrations being at plasma level or higher. These results suggest that not (-)-menthol itself, but one or several of its neutral metabolites inhibit the bone resorbing cells in vivo.
authors.affiliation: Laboratory for Phytopharmacology, Bioanalytics & Pharmacokinetics, Department of Clinical Research, University of Bern, Bern, Switzerland.
authors.forename: Miriam
authors.initials: M
authors.lastname: Spichiger
authors.forename: Rudolf
authors.initials: R
authors.lastname: Brenneisen
authors.forename: Rolf
authors.initials: R
authors.lastname: Felix
authors.forename: Roman C
authors.initials: RC
authors.lastname: Mühlbauer
mesh_terms: D000284:Administration, Oral; D000818:Animals; D019540:Area Under Curve; D001862:Bone Resorption / Q000097:blood*; D001842:Bone and Bones / Q000166:cytology / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D008401:Gas Chromatography-Mass Spectrometry; D008297:Male; D027541:Mentha; D008610:Menthol / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000652:urine; D009924:Organ Culture Techniques; D010789:Phototherapy; D010936:Plant Extracts / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000652:urine; D051381:Rats; D017208:Rats, Wistar
chemical_list: D010936:Plant Extracts; D008610:Menthol