Prophylactic efficacy of patchoulene epoxide against ethanol-induced gastric ulcer in rats: Influence on oxidative stress, inflammation and apoptosis

Chem Biol Interact. 2018 Mar 1:283:30-37. doi: 10.1016/j.cbi.2018.01.014. Epub 2018 Jan 12.

Abstract

Patchoulene epoxide (PAO), a tricyclic sesquiterpene isolated from the long-stored patchouli oil, has been demonstrated the anti-inflammatory activity in vivo based on our previous study. However, the gastric protective effect of PAO still remains unknown. Therefore, in the present study, ethanol-induced gastric ulcer model was carried out to evaluate the anti-ulcerogenic activity of PAO and to elucidate the potential mechanisms that involves. According to our results, macroscopic examination revealed that PAO could significantly reduce ethanol-induced gastric ulcer areas as compared with the vehicle group, which was also supported by the histological evaluation result. As for its potential mechanism, the anti-inflammatory activity of PAO contributed to gastric protection through reversing the imbalance between pro- and anti-inflammatory cytokines and modulating the expressions of NF-κB pathway-related proteins including p-IκBα, IκBα, p-p65 and p65. Besides, PAO was able to enhance the expressions of antioxidant enzymes including glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT), and down-regulate malonaldehyde (MDA), an indicator of lipid peroxidation. Furthermore, immunohistochemistry analysis exhibited potent anti-apoptosis effect of PAO, as evidence by down-regulating the protein expression of caspase-3, Fas and Fasl. Additionally, we also demonstrated that PAO could replenish PGE2 and NO mucosal defense. In conclusion, these findings suggested that PAO has gastric protective activity against ethanol and this might be related to its influence on inflammatory response, oxidative stress, apoptosis cascade and gastric mucosal defense.

Keywords: Apoptosis; Gastric ulcer; Inflammatory response; Oxidative stress; Patchoulene epoxide.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / chemistry
  • Anti-Inflammatory Agents / pharmacology*
  • Anti-Inflammatory Agents / therapeutic use
  • Apoptosis / drug effects*
  • Caspase 3 / metabolism
  • Catalase / metabolism
  • Cytokines / analysis
  • Cytokines / metabolism
  • Down-Regulation / drug effects
  • Ethanol / toxicity
  • Inflammation / prevention & control
  • Lipid Peroxidation / drug effects
  • Male
  • Oxidative Stress / drug effects*
  • Plant Oils / chemistry
  • Pogostemon / chemistry
  • Pogostemon / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Sesquiterpenes / chemistry
  • Sesquiterpenes / pharmacology*
  • Sesquiterpenes / therapeutic use
  • Stomach / pathology
  • Stomach Ulcer / chemically induced
  • Stomach Ulcer / pathology
  • Stomach Ulcer / prevention & control*
  • Superoxide Dismutase / metabolism

Substances

  • Anti-Inflammatory Agents
  • Cytokines
  • Plant Oils
  • Sesquiterpenes
  • Ethanol
  • Catalase
  • Superoxide Dismutase
  • Caspase 3