1. Academic Validation
  2. (-)-Myrtenol accelerates healing of acetic acid-induced gastric ulcers in rats and in human gastric adenocarcinoma cells

(-)-Myrtenol accelerates healing of acetic acid-induced gastric ulcers in rats and in human gastric adenocarcinoma cells

  • Eur J Pharmacol. 2019 Jul 5:854:139-148. doi: 10.1016/j.ejphar.2019.04.025.
Ana Flavia S C Viana 1 Miriam Teresa P Lopes 2 Francisca Tuelly B Oliveira 3 Paulo Iury G Nunes 3 Verlane G Santos 2 Ariadne D Braga 2 Ana Cândida A Silva 2 Damião P Sousa 4 Daniel A Viana 5 Vietla S Rao 3 Rita de Cássia M Oliveira 6 Flavia A Santos 3
Affiliations

Affiliations

  • 1 Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceará, Fortaleza, Ceará, Brazil; Medicinal Plants Research Center, Health Sciences Center, Federal University of Piauí, Teresina, Piauí, Brazil. Electronic address: [email protected].
  • 2 Department of Pharmacology, Laboratory of Antitumor Substances, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
  • 3 Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceará, Fortaleza, Ceará, Brazil.
  • 4 Department of Pharmaceutical Sciences, Federal University of Paraiba, João Pessoa, Paraiba, Brazil.
  • 5 Laboratory of Pathology and Legal Medicine, Faculty of Veterinary Science, State University of Ceará, Fortaleza, Ceará, Brazil.
  • 6 Medicinal Plants Research Center, Health Sciences Center, Federal University of Piauí, Teresina, Piauí, Brazil.
Abstract

The gastroprotective property of (-)-myrtenol, a monoterpenoid, has been demonstrated previously against acute gastric ulceration induced by ethanol. However, the healing property of (-)-myrtenol in a chronic gastric ulcer model remains to be verified. This study evaluated its healing efficacy and the mechanism involved using the rat model of chronic gastric ulcer induced by serosal injection of 80% acetic acid in vivo, and human gastric adenocarcinoma cells (AGS) in vitro. The results showed that compared to vehicle-treated ulcer controls, oral administration of (-)-myrtenol (50 and 100 mg/kg/day) for 7 days promoted ulcer healing, as indicated by significant decreases in ulcer area and volume. The macroscopic and microscopic findings confirmed the healing potential of (-)-myrtenol. The ulcer healing activity was also associated with significant increases in gastric Mucin content, collagen deposition, number of cells with positive marking for proliferating cell nuclear antigen (PCNA), and by changes in the expression of the inflammatory parameters tumor necrosis factor (TNF)-α, interleukin (IL)-1β and cyclooxygenase (COX)-2, as well as a decrease of metalloproteinases (MMP-9 and MMP-2) activity. Furthermore, in vitro assays using the AGS cultures revealed that (-)-myrtenol favors wound healing activity via stimulation of cell proliferation and migration without altering the cell viability. Taken together, these findings indicate that (-)-myrtenol has gastro-cytoprotective and ulcer healing properties that can be further explored to develop a new therapeutic agent from a natural source for the treatment of gastric ulcer.

Keywords

(−)-Myrtenol; AGS cells; Acetic acid-induced gastric ulcer; Cell migration; Cell proliferation; Ulcer healing.

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