title: Protective effect of eugenol against restraint stress-induced gastrointestinal dysfunction: Potential use in irritable bowel syndrome.
abstract: BACKGROUND
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Neurotherapeutics Laboratory, Department of Pharmaceutics, Indian Institute of Technology (Banaras Hindu University) , Varanasi, Uttar Pradesh , India.
authors.forename: Debapriya
authors.initials: D
authors.lastname: Garabadu
authors.forename: Ankit
authors.initials: A
authors.lastname: Shah
authors.forename: Sanjay
authors.initials: S
authors.lastname: Singh
authors.forename: Sairam
authors.initials: S
authors.lastname: Krishnamurthy
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D005054:Eugenol / Q000494:pharmacology / Q000627:therapeutic use*; D043183:Irritable Bowel Syndrome / Q000188:drug therapy* / Q000378:metabolism* / Q000523:psychology; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D020011:Protective Agents; D051381:Rats; D012149:Restraint, Physical; D013315:Stress, Psychological / Q000188:drug therapy* / Q000378:metabolism* / Q000523:psychology; D016896:Treatment Outcome
chemical_list: D020011:Protective Agents; D005054:Eugenol
keywords: Amygdala; corticosterone; monoamine; oxidative stress; pre-frontal cortex