Planta Med 2006; 72(14): 1290-1295
DOI: 10.1055/s-2006-951681
Original Paper
Pharmacology
© Georg Thieme Verlag KG Stuttgart · New York

The Inhibition of Bone Resorption in Rats Treated with (-)-Menthol is Due to its Metabolites

Miriam Spichiger1 , 2 , Rudolf Brenneisen1 , Rolf Felix2 , Roman C. Mühlbauer2
  • 1Laboratory for Phytopharmacology, Bioanalytics & Pharmacokinetics, Department of Clinical Research, University of Bern, Bern, Switzerland
  • 2Bone Biology Group, Department of Clinical Research, University of Bern, Bern, Switzerland
Further Information

Publication History

Received: January 26, 2006

Accepted: August 12, 2006

Publication Date:
04 October 2006 (online)

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.

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Prof. Dr. Rudolf Brenneisen

Laboratory for Phytopharmacology, Bioanalytics & Pharmacokinetics

Department of Clinical Research

University of Bern

Murtenstrasse 35

3010 Bern

Switzerland

Phone: +41-31-632-8714

Fax: +41-31-632-8721

Email: rudolf.brenneisen@dkf.unibe.ch