• Protective effects of oleuropein against acute and chronic stress-induced anxiety and depression by reducing oxidative stress, serum corticosterone, and expression of IL-6 and mGluR1 genes
  • mahbubeh setorki,1,*
    1. Department of Biology, Izeh Branch, Islamic Azad University, Izeh, Iran


  • Introduction: Background: Various studies on oleuropein have shown that this compound has various neuroprotective properties in various neurological disorders, including neurological hippocampal damage during brain ischemia, hypoxic brain damage and re-oxygenation in mouse model of diabetes, audiogenic seizure related to high-fat diet, spinal cord injury in rat model, andneurotoxicities. The neuroprotective property of this compound is due to its free radical- and lipid peroxidationinhibiting, anti-inflammatory, glutathione restoring, and anti-apoptotic properties. The aim of this study was to investigate the efficacy of oleuropein on anxiety and epression in mice under acute and chronic stress
  • Methods: Methods: To induce acute restraint stress (ARS) in mice, they were exposed to immobility stress in restrainer once and to induce chronic restraint stress (CRS) twice for two hours daily for two weeks and then to a 2-min, 0.5-mA electrical shock. Mice under ARS and CRS were divided into 5 groups consisting of control (receiving drug solvent), treatments (oleuropein at 7.5, 15, 30 mg/kg), and positive control (diazepam).
  • Results: Results: In mice under ARS, 30 mg/kg of oleuropein increased the time on the open arms and decreased the time on the closed arms of elevated plus maze (EPM) (P<0.05). In mice under CRS, 30 mg/kg of oleuropein increased the number of entries into the open arms and the time on the open arms (P<0.05). In mice under ARS, all three doses of oleuropein significantly reduced immobility in the tail suspension test (TST) and forced swim test (FST) (P<0.05), and in those under CRS,oleuropein at 15 mg/kg significantly reduced immobility duration in the TST and, at 15 and 30 mg/kg, significantly decreased immobility duration in the FST (P<0.05). Oleuropein treatment did not significantly affect the behavior of mice under ARS, but oleuropein at 7.5 mg/kg decreased the number of entries into the margins in the open field test (P<0.05). Administration of different doses of oleuropein reduced lipid peroxidation and increased antioxidant capacity of brain and serum in mice under ARS and CRS (P<0.05). Oleuropein also reduced corticosterone levels in mice under CRS mice and decreased the expression of IL-6 gene and metabotropic glutamate receptor type 1 (mGluR1) in mice under ARS and CRS.
  • Conclusion: Conclusion: In this study, the administration of different doses of oleuropein reduced the anxietyand depression-like behaviors in mice under acute and chronic stress. Oleuropein also reduced lipid peroxidation and increased antioxidant capacity of the brain and serum in mice under acute and chronic stress. In mice under acute and chronic stress that received oleuropein, mGluR1 and IL-6 gene expression also reduced. Therefore, it seems that the antidepressant and anxiolytic effects of oleuropein are due to the reduction of oxidative stress, inflammation of the brain, and the modulation of glutaminergic signaling pathway.
  • Keywords: Key words: oleuropein, depression, anxiety, stress