Effects of isopentyl ferulate on oxidative stress biomarkers and a possible GABAergic anxiolytic-like trait in Swiss mice

This study aimed to evaluate the anxiolytic-like effect and the possible neuronal mechanism of action of isopentyl ferulate (IF). For this purpose, we used the marble burying test in Swiss albino mice. The biomarkers involved in oxidative stress were measured in the hippocampus homogenate of the test animals. In addition, the toxicity and antioxidant capacities were tested in Artemia salina and rat erythrocytes, respectively. The results suggest that, an acute administration of the IF at doses of 25, 50, 75 and 150 mg/kg (intraperitoneal, i.p.) significantly (p < 0.05) reduced the marble burying behavior of the animals as compared to the vehicle group, which demonstrates a calming effect of this chemical. It was observed that, the pre-treatment with flumazenil (2.5 mg/kg, i.p.), an antagonist of the gamma-amino butyrinc acid (GABAA) receptor, significantly reversed the marble burying behavioral activity in the animals treated with the IF 150 mg/kg dose. Moreover, the reduction in nitrite content and lipid peroxidation levels, while an increased in the reduced glutathione (GSH), glutathione peroxidase (GPx), superoxide dismutase (SOD) and catalase (CAT) activities were also observed their hippocampus. Although, IF (2.36-14.16 mM) did not show toxicity in A. salina but exhibited a prominent antioxidant capacity in hydrogen peroxide-induced oxidative damage in rat erythrocytes. In conclusion, IF exhibited an anxiety-like effect in mice along with a potent antioxidant capacity, and we suppose it may have neuroprotective effects possibly via GABAergic transmission pathway.