Eugenol as an anti-stress agent: Modulation of hypothalamic–pituitary–adrenal axis and brain monoaminergic systems in a rat model of stress

Abstract

Stress is the leading psychopathological cause for several mental disorders. Physiological and psychological responses to stress are mediated by the hypothalamic?pituitary?adrenal (HPA), sympathoadrenal system (SAS), and brain monoaminergic systems (BMS). Eugenol is reported to substantially modulate brain functions by regulating voltage-gated cation channels and release of neurotransmitters. This study was designed to evaluate the anti-stress effect of eugenol in the 4-h restraint model using rats. Ulcer index was measured as a parameter of the stress response. HPA axis and the SAS were monitored by estimating plasma corticosterone and norepinephrine (NE), respectively. Analysis of NE, serotonin (5-HT), dopamine, and their metabolites in discrete brain regions was performed to understand the role of BMS in the anti-stress effect of eugenol. Stress exposure increased the ulcer index as well as plasma corticosterone and NE levels. Eugenol pretreatment for 7 days decreased the stress-induced increase in ulcer index and plasma corticosterone but not NE levels, indicating a preferential effect on the HPA axis. Furthermore, eugenol showed a ?U?-shaped dose?response curve in decreasing ulcer index and plasma corticosterone levels. Eugenol also reversed the stress-induced changes in 5-HT levels in all brain regions, whereas NE levels were reversed in all brain regions except hippocampus. These results suggest that eugenol possesses significant anti-stress activity in the 4-h restraint model and the effect is due to modulation of HPA and BMS.

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

“…They are altered in different brain regions such as hippocampus, hypothalamus, PFC, and amygdala in both stress and IBS conditions p50.05 compared with RS+OÀ4 (one-way ANOVA followed by the Student Newman-Keuls test). (Garabadu et al, 2011;Greenwood-Van Meerveld et al, 2001). Here, eugenol per se did not cause any change in the monoaminergic system in any brain regions of normal animals.…”

“…The plasma level of corticosterone was estimated in control, stress control, and eugenol (50 mg/kg) group animals using HPLC with an ultraviolet detector (Garabadu et al, 2011;Woodward & Emery, 1987).…”

“…The brain was microdissected (Palkovits & Brownstein, 1988) into hippocampus, hypothalamus, PFC, and amygdala and, the level of neurotransmitters and their metabolites were estimated in discrete brain regions using HPLC with an electrochemical detector (Garabadu et al, 2011;Kim et al, 1987).…”

“…Eugenol has been reported to have several neuropharmacological activities such as anxiolytic, antidepressant, and neuroprotection against N-methyl-D-aspartic acid-induced neurotoxicity in experimental animal models (Ardjmand et al, 2006;Garabadu et al, 2011). Eugenol has been reported to show an anti-stress effect by modulating HPA-axis and the brain monoamine system in experimental animals (Garabadu et al, 2011). As eugenol exhibits anti-stress and neuroprotective activities, we assumed that it may have a protective effect against the restraint stress (RS)-induced animal model of irritable bowel syndrome (IBS).…”

Neuroprotective effects of eugenol against aluminiuminduced toxicity in the rat brain

“…In addition, a direct neurotrophic effect of eugenol on BDNF was previously reported since the administration of eugenol in drinking water for two consecutive weeks to male mice induced BDNF gene expression in the hippocampus (47). Similarly, eugenol was able to reverse the stress-induced changes of serotonin level in all rat brain regions and such modulation in brain functions is attributed to the ability of eugenol to regulate voltage-gated cation channels and the release of neurotransmitters (48). Taken altogether, eugenol exerts a multitude of actions, either directly or indirectly, to restore a normal neurotrophic and serotonergic balance in the brain of Al-intoxicated rats.…”