(-)-Carveol Prevents Gastric Ulcers via Cytoprotective, Antioxidant, Antisecretory and Immunoregulatory Mechanisms in Animal Models

Abstract

Background: (-)-Carveol (p-Mentha-6,8-dien-2-ol) is a monocyclic monoterpenic alcohol, present in essential oils of plant species such as Cymbopogon giganteus, Illicium pachyphyllum and in spices such as Carum carvi (cumin). Pharmacological studies report its antitumor, antimicrobial, neuroprotective, vasorelaxant, antioxidant and anti-inflammatory activity.Hypothesis/Purpose: The objective of this study was to evaluate the acute non-clinical oral toxicity, gastroprotective activity of monoterpene (-)-Carveol in animal models and the related mechanisms of action.Methods: Acute toxicity was assessed according to OECD guide 423 in mice. Ethanol, stress, NSAIDs and pylorus ligation-induced gastric ulcer models were used to investigate antiulcer properties. The related mechanisms of action were using the ethanol-gastric lesions protocol.Results: (-)-Carveol has low toxicity, with a lethal dose 50% (LD50) equal to or greater than 2,500 mg/kg according to OECD guide nº 423. In all gastric ulcer induction methods evaluated, (-)-Carveol (25, 50, 100 and 200 mg/kg, p.o.) significantly reduced the ulcerative lesion in comparison with the respective control groups. To investigate the mechanisms involved in the gastroprotective activity, the antisecretory or neutralizing of gastric secretion, cytoprotective, antioxidant and immunoregulatory effects were evaluated. In the experimental protocol of pylorus ligation-induced gastric ulcer, (-)-Carveol (100 mg/kg) reduced (p < 0.001) the volume of gastric secretion in both routes (oral and intraduodenal). The previous administration of blockers NEM (sulfhydryl groups blocker), L-NAME (nitric oxide synthesis inhibitor), glibenclamide (KATP channel blocker) and indomethacin (cyclo-oxygenase inhibitor), significantly reduced the gastroprotection exercised by (-)-Carveol, suggesting the participation of these pathways in its gastroprotective activity. In addition, treatment with (-)-Carveol (100 mg/kg) increased (p < 0.001) mucus adhered to the gastric wall. Treatment also increased (p < 0.001) levels of reduced glutathione (GSH), superoxide dismutase (SOD) and interleukin-10 (IL-10). It also reduced (p < 0.001) malondialdehyde (MDA), myeloperoxidase (MPO), interleukin-1 beta (IL-1β) and tumor necrosis factor-alpha (TNF-α) levels.Conclusion: Thus, it is possible to infer that (-)-Carveol presents gastroprotective activity related to antisecretory, cytoprotective, antioxidant and immunomodulatory mechanisms.

Protective Effect of Foxtail Millet Protein Hydrolysate on Ethanol and Pyloric Ligation-Induced Gastric Ulcers in Mice

“…Next, the abovementioned ethanol-induced gastric ulcer mouse model was established. Mice were pretreated with the blocking agents N-nitro-L-arginine methyl ester (L-NAME), N-ethylmaleimide (NEM), glibenclamide, and indomethacin before the ethanol gavage [ 25 ]. Each blocking agent corresponded to 2 groups of mice, one of which was the FPH gavage group and the other was the vehicle gavage group, for a total of 8 groups.…”

“…To investigate the involvement of KATP channels in the gastroprotection of FPH, mice were pretreated with glibenclamide (5 mg/kg, i.p.) [ 25 , 26 ].…”

Bioactive properties of the aromatic molecules of spearmint (Mentha spicataL.) essential oil: a review

“…155 Evaluation the acute non-clinical oral toxicity of carveol shows that LD 50 is equal to or greater than 2500 mg kg −1 . 16 The LD 50 of orally administered dihydrocarvone, dihydrocarveol and dihydrocarvyl acetate in rat is all greater than 5 g kg −1 . 152–154 A summary of the toxicological information of spearmint aromatic molecules is presented in Table 4.…”

“…The authors concluded that the gastroprotective activity of carveol may be related to antisecretory, cytoprotective, antioxidant and immunomodulatory mechanisms. 16…”

“…Carveol exists in essential oils of orange peel, dill, caraway seeds and various plants including Cymbopogon giganteus , Illicium pachyphyllum and C. carvi . 15,16 Dihydrocarvone, also known as 2-methyl-5-(1-methylethenyl)-cyclohexanone, is a ketone resulting from the reduction of the endocyclic cyclohexene double bond. This compound is a clear and colourless liquid, having a herbaceous and spearmint-like odour.…”