An in silico investigation of menthol metabolism

PLoS One. 2019 Sep 27;14(9):e0216577. doi: 10.1371/journal.pone.0216577. eCollection 2019.

Abstract

Prevalence of mentholated products for consumption has brought great importance to studies on menthol's metabolic pathways to ensure safety, design more potent derivatives, and identify therapeutic benefits. Proposed pathways of (-)-menthol metabolism based on metabolites found experimentally in previous works by Yamaguchi, Caldwell & Farmer, Madyastha & Srivatsan and Hiki et al. were not in agreement. This in silico approach is based on the three in vivo studies and aims to resolve the discrepancies. Reactions in the pathways are conjugation with glucuronic acid/sulfate, oxidation to alcohol, aldehyde & carboxylic acid, and formation of a four-membered/five-membered ring. Gas-phase structures, standard Gibbs energies and SMD solvation energies at B3LYP/6-311++G(d,p) level were obtained for 102 compounds in the pathways. This study provides a more complete picture of menthol metabolism by combining information from three experimental studies and filling missing links in previously published pathways.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Computer Simulation*
  • Humans
  • Menthol / adverse effects
  • Menthol / pharmacokinetics*
  • Rats

Substances

  • Menthol

Grants and funding

T.L. received research funding from the Institute for the Promotion of Teaching Science and Technology (www.ipst.ac.th contract no. 08/2557). The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.