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Evidence-Based Complementary and Alternative Medicine
Volume 2013 (2013), Article ID 217853, 10 pages
Research Article

Novel Antidepressant-Like Activity of Propolis Extract Mediated by Enhanced Glucocorticoid Receptor Function in the Hippocampus

1Division of Bio-Imaging, Chuncheon Center, Korea Basic Science Institute, Chuncheon 200-701, Republic of Korea
2Acupuncture & Meridian Science Research Center, College of Oriental Medicine, Kyung Hee University, Seoul 130-701, Republic of Korea
3Laboratory of Neuropharmacology, Department of Nursing, Shikoku University, School of Health Sciences, Tokushima 771-1192, Japan

Received 3 January 2013; Accepted 3 June 2013

Academic Editor: Zenon Czuba

Copyright © 2013 Mi-Sook Lee et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


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.