Effect of Menthol in Experimentally Induced Ulcers: Pathways of Gastroprotection

Chem Biol Interact. 2013 Nov 25;206(2):272-8. doi: 10.1016/j.cbi.2013.10.003. Epub 2013 Oct 9.


Based on ethnopharmacological indications that Mentha species may be used in the treatment of gastrointestinal diseases, this study aimed to characterize the gastroprotective mechanisms of menthol (ME), the major compound of the essential oil from species of the genus Mentha. The gastroprotective action of ME was analyzed in gastric ulcers that were induced by ethanol or indomethacin in Wistar male rats. The mechanisms responsible for the gastroprotective effect were assessed by analyzing the amount of mucus secreted, involvement of non-protein sulfhydryl (NP-SH) compounds, involvement of calcium ion channels and NO/cGMP/K(+)ATP pathway, gastric antisecretory activity and the prostaglandin E2 (PGE2) production. The anti-diarrheal activity and acute toxicity of ME were also evaluated. Oral treatment with ME (50mg/kg) offered 88.62% and 72.62% of gastroprotection against ethanol and indomethacin, respectively. There was an increased amount of mucus and PGE2 production. The gastroprotective activity of ME involved NP-SH compounds and the stimulation of K(+)ATP channels, but not the activation of calcium ion channels or the production of NO. The oral administration of ME induced an antisecretory effect as it decreased the H(+) concentration in gastric juice. ME displayed anti-diarrheal and antiperistaltic activity. There were no signs of toxicity in the biochemical analyses performed in the rats' serum. These results demonstrated that ME provides gastroprotective and anti-diarrheal activities with no toxicity in rats.

Keywords: Acute toxicity; Diarrhea; Gastric ulcer; Gastroprotection; Menthol.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / toxicity
  • Calcium Channels / metabolism
  • Castor Oil / toxicity
  • Cyclic GMP / metabolism
  • Diarrhea / chemically induced
  • Diarrhea / pathology
  • Dinoprostone / metabolism
  • Ethanol / toxicity
  • Indomethacin / toxicity
  • Male
  • Menthol / pharmacology*
  • Nitric Oxide / metabolism
  • Potassium Channels / metabolism
  • Rats
  • Rats, Wistar
  • Signal Transduction / drug effects
  • Stomach Ulcer / chemically induced
  • Stomach Ulcer / pathology*
  • Sulfhydryl Compounds / metabolism


  • Anti-Inflammatory Agents, Non-Steroidal
  • Calcium Channels
  • Potassium Channels
  • Sulfhydryl Compounds
  • Menthol
  • Nitric Oxide
  • Ethanol
  • Castor Oil
  • Cyclic GMP
  • Dinoprostone
  • Indomethacin