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

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 stressinduced 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.

UPLC-Q-TOF/MS-based metabonomic studies on the intervention effects of aspirin eugenol ester in atherosclerosis hamsters

“…The non-selective inhibitation of aspirin on both COX-1 and COX-2 is considered to be an underlying reason for the gastrointestinal side effects. Accumulated evidence indicates that eugenol displays antiulcer activities, in which eugenol can dose-dependently reduce gastric ulcers in rat gastric ulcer models 32 – 34 . Eugenol can also stimulate the synthesis of mucus, an important gastroprotective factor, which may be responsible for antiulcer activity.…”

Pathogenesis, Experimental Models and Contemporary Pharmacotherapy of Irritable Bowel Syndrome: Story About the Brain-Gut Axis

“…Henceforth, comparative examinations of electrophysiological as well as behavioral responses are often performed upon colorectal distention in research studies. With the aid of such setup, the effects of therapeutics can be evaluated according to the visceromotor responses or visceral nociception of the experimental subjects whereas components of the visceral pain pathway can be identified [ 62 ]. However, the main concern of this visceral pain model is the construction of the distending apparatus.…”

Nesfatin-1 in the dorsal raphe nucleus influences visceral sensitivity via 5-HT neurons in male maternally separated rats

“…IBS is recognized as a stress-related disorder 20 , 21 . Stress scores are higher in patients with IBS than with other functional bowel disorders, and stress is also significantly correlated with IBS symptoms 21 .…”