Protective effect of eugenol against restraint stress-induced gastrointestinal dysfunction: Potential use in irritable bowel syndrome

Pharm Biol. 2015 Jul;53(7):968-74. doi: 10.3109/13880209.2014.950674. Epub 2014 Dec 4.

Abstract

Context: Eugenol, an essential constituent found in plants such as Eugenia caryophyllata Thunb. (Myrtaceae) is reported to possess neuroprotective and anti-stress activities. These activities can potentially be useful in the treatment of stress-induced irritable bowel syndrome (IBS).

Objective: The protective effect of eugenol was assessed against restraint stress (RS)-induced IBS-like gastrointestinal dysfunction in rats. Further, its centrally mediated effect was evaluated in this model.

Materials and methods: Eugenol (12.5, 25, and 50 mg/kg), ondansetron (4.0 mg/kg, p.o.), and vehicle were administered to rats for 7 consecutive days before exposure to 1 h RS. One control group was not exposed to RS-induction. The effect of eugenol (50 mg/kg) with and without RS exposure was evaluated for mechanism of action and per se effect, respectively. The hypothalamic-pituitary-adrenal cortex (HPA)-axis function was evaluated by estimating the plasma corticosterone level. The levels of brain monoamines, namely serotonin, norepinephrine, dopamine, and their metabolites were estimated in stress-responsive regions such as hippocampus, hypothalamus, pre-frontal cortex (PFC), and amygdala. Oxidative damage and antioxidant defenses were also assessed in brain regions.

Results: Eugenol (50 mg/kg) reduced 80% of RS-induced increase in fecal pellets similar to that of ondansetron. Eugenol attenuated 80% of stress-induced increase in plasma corticosterone and modulated the serotonergic system in the PFC and amygdala. Eugenol attenuated stress-induced changes in norepinephrine and potentiated the antioxidant defense system in all brain regions.

Conclusion: Eugenol protected against RS-induced development of IBS-like gastrointestinal dysfunction through modulation of HPA-axis and brain monoaminergic pathways apart from its antioxidant effect.

Keywords: Amygdala; corticosterone; monoamine; oxidative stress; pre-frontal cortex.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Dose-Response Relationship, Drug
  • Eugenol / pharmacology
  • Eugenol / therapeutic use*
  • Irritable Bowel Syndrome / drug therapy*
  • Irritable Bowel Syndrome / metabolism*
  • Irritable Bowel Syndrome / psychology
  • Male
  • Oxidative Stress / drug effects
  • Oxidative Stress / physiology
  • Protective Agents
  • Rats
  • Restraint, Physical
  • Stress, Psychological / drug therapy*
  • Stress, Psychological / metabolism*
  • Stress, Psychological / psychology
  • Treatment Outcome

Substances

  • Protective Agents
  • Eugenol