Monoaminergic system is implicated in the antidepressant-like effect of hyperoside and protocatechuic acid isolated from Impatiens glandulifera Royle in mice.

We have recently demonstrated that the hydroethanolic extracts of Impatiens glandulifera Royle (Balsaminaceae) have antianxiety effect in mice. The present study was aimed to investigate an antidepressant activity of hyperoside (HYP) and protocatechuic acid (PCA), two polyphenols isolated from the aerial parts of this plant, using the forced swimming test (FST) and tail suspension test (TST) in mice. The implication of the monoaminergic system in this effect was assessed and brain-derived neurotrophic factor (BDNF) expression was measured. At doses 1.875, 3.75 and 7.5 mg/kg, HYP and PCA significantly reduced immobility in the FST and TST, without affecting locomotor activity of mice. Pretreatment with p-chlorophenylalanine (PCPA 100 mg/kg, a serotonin synthesis inhibitor) or α-methyl-DL-tyrosine (AMPT 100 mg/kg, a catecholamine synthesis inhibitor) was able to prevent antidepressant-like effect of HYP and PCA (3.75 mg/kg). Sub-effective doses of fluoxetine (5 mg/kg) or reboxetine (2 mg/kg) were capable of potentiating the effect of a sub-effective dose of HYP (0.94 mg/kg) in the FST. Co-administration of sub-effective dose of PCA (0.94 mg/kg) and reboxetine (2 mg/kg) resulted in reducing immobility in the FST. The antidepressant-like effect of HYP and PCA was also prevented by the administration of sulpiride (50 mg/kg), a D2 antagonist. In addition, HYP (3.75 and 7.5 mg/kg) and PCA (7.5 mg/kg) improved the expression of hippocampal BDNF of mice subjected to TST. Altogether, our findings suggest that HYP and PCA exert antidepressant-like effects in mice, which was possibly mediated by monoaminergic system and the upregulation of BDNF level.

α-Tocopherol Ameliorates Redox Equilibrium and Reduces Inflammatory Response Caused by Chronic Variable Stress.

Chronic exposure to stress factors contributes to the development of depression by generating excess of reactive oxygen species which leads to oxidative stress and inflammatory processes. The aim of the study was to assess the potential protective properties of α-tocopherol supplementation on the rats exposed to chronic variable stress (CVS). Male Wistar rats (50-55 days old, weighing 200-250 g) were divided into three groups (n=10): control, stressed, and stressed and receiving (+)-α-tocopherol solution in a dose of 100 mg/kg/day. Rats in the stressed groups were exposed to CVS for 40 days. Markers of redox disorders (glutathione reduced and oxidized levels, GSH/GSSG ratio, glutathione peroxidase, glutathione reductase activities, total antioxidant status, and lipid peroxidation) and inflammatory response (IL-1ß, IL6, and TNF-α) were determined in the blood. Additionally, molecular biomarkers of depression (expression of Fkbp5 and Tph2) were studied in hippocampus. The biochemical analysis was inconclusive about the presence of oxidative stress in the blood of rats exposed to CVS. However, changes in all parameters suggest presence of redox equilibrium disorders. Similarly, activation of inflammatory processes was observed as a result of CVS. Molecular effects of environmental stress in hippocampus were also observed. Generally, α-tocopherol ameliorated redox equilibrium disorders, tempered inflammatory response, and protected from changes in determined molecular markers of depression.