Abstract

Propolis is a natural product made by honeybees that has been widely used in folk medicine with a broad spectrum of biological activities. To investigate the antidepressant-like activity of propolis extract, CD-1 mice were administered an ethanol extract of propolis (50, 100, or 200 mg/kg, p.o.) prior to the behavioral test. The propolis extract-treated group showed a dose-dependent decrease in immobility time in the FST and tail suspension test without altering locomotor activity. Propolis extract decreased the limbic hypothalamic-pituitary-adrenal axis response to the FST as indicated by an attenuated corticosterone response and decreased in c-fos immunoreactive neurons in the hippocampal dentate gyrus. Western blot analysis revealed a reduction in hippocampal glucocorticoid receptor (GR) expression following the FST, which was reversed by propolis extract. Propolis extract also increased pGR(S220)/(S234) ratio by a differential phosphorylation in S220 and S234. FST-induced downregulation of cAMP-responsive element binding protein phosphorylation at S133 (pCREB) was restored by propolis extract, showing a strong and positive relationship between pCREB and pGR(S220)/(S234) ratio. These findings suggest that the propolis extract potentiates antidepressant-like activity by enhancing GR function which is one of the therapeutic mechanisms of antidepressant; thus, propolis extract may provide a novel therapy for depression.

Highlights

  • Propolis is a resinous substance collected by honeybees from various plants

  • A significant effect of treatment was found for the FSTinduced behaviors of immobility time (Figure 1(a), F4,45 = 5.15, P < 0.01) and swimming (Figure 1(b), F4,45 = 2.96, P < 0.05)

  • The post hoc test revealed that propolis extract (100 and 200 mg/kg) decreased immobility time during the forced swim test (FST) in a dose-dependent manner compared with vehicle treatment (P < 0.05; P < 0.01, resp.)

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Summary

Introduction

Propolis is a resinous substance collected by honeybees from various plants. It contains more than 200 natural constituents including polyphenols, phenolic aldehydes, sequiterpenequinones, coumarins, amino acids, fatty acids, steroids, and inorganic compounds [1]. Recent studies have shown that propolis essential oil has an anxiolytic effect on an acutely stressed mouse model through modulation of the hypothalamic-pituitary-adrenal (HPA) axis [8, 9]. This finding suggests that propolis has antidepressant-like effect, but this role of the substance has not been investigated

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