title: Novel antidepressant-like activity of caffeic Acid phenethyl ester is mediated by enhanced glucocorticoid receptor function in the hippocampus.
abstract: Caffeic acid phenethyl ester (CAPE) is an active component of propolis that has a variety of potential pharmacological effects. Although we previously demonstrated that propolis has antidepressant-like activity, the effect of CAPE on this activity remains unknown. The present study assessed whether treatment with CAPE (5, 10, and 20 µmol/kg for 21 days) has an antidepressant-like effect in mice subjected to chronic unpredictable stress via tail suspension (TST) and forced swim (FST) tests. CAPE administration induced behaviors consistent with an antidepressant effect, evidenced by decreased immobility in the TST and FST independent of any effect on serum corticosterone secretion. Western blots, conducted subsequent to behavioral assessment, revealed that CAPE significantly decreased glucocorticoid receptor phosphorylation at S234 (pGR(S234)), resulting in an increased pGR(S220/S234) ratio. We also observed negative correlations between pGR(S220)/(S234) and p38 mitogen-activated protein kinase (p38MAPK) phosphorylation, which was decreased by CAPE treatment. These findings suggest that CAPE treatment exerts an antidepressant-like effect via downregulation of p38MAPK phosphorylation, thereby contributing to enhanced GR function.
authors.affiliation: Division of Bio-Imaging, Chuncheon Center, Korea Basic Science Institute, Chuncheon 200-701, Republic of Korea ; Department of Science in Korean Medicine, Graduate School, College of Korean Medicine, Kyung Hee University, Seoul 130-701, Republic of Korea.
authors.forename: Mi-Sook
authors.initials: MS
authors.lastname: Lee
authors.affiliation: Division of Bio-Imaging, Chuncheon Center, Korea Basic Science Institute, Chuncheon 200-701, Republic of Korea.
authors.forename: Young Han
authors.initials: YH
authors.lastname: Kim
authors.affiliation: Division of Bio-Imaging, Chuncheon Center, Korea Basic Science Institute, Chuncheon 200-701, Republic of Korea.
authors.forename: Bo-Ram
authors.initials: BR
authors.lastname: Lee
authors.affiliation: Division of Bio-Imaging, Chuncheon Center, Korea Basic Science Institute, Chuncheon 200-701, Republic of Korea.
authors.forename: Seung-Hae
authors.initials: SH
authors.lastname: Kwon
authors.affiliation: Gwangju Center, Korea Basic Science Institute, Gwangju 500-757, Republic of Korea.
authors.forename: Won-Jin
authors.initials: WJ
authors.lastname: Moon
authors.affiliation: MR Research Center, Korea Basic Science Institute, Cheongwon 363-883, Republic of Korea.
authors.forename: Kwan-Su
authors.initials: KS
authors.lastname: Hong
authors.affiliation: College of Pharmacy, Sookmyung Women's University, Seoul 140-742, Republic of Korea.
authors.forename: Yun Seon
authors.initials: YS
authors.lastname: Song
authors.affiliation: Laboratory of Neuropharmacology, Department of Nursing, School of Health Sciences, Shikoku University, Tokushima 771-1192, Republic of Korea.
authors.forename: Kyoji
authors.initials: K
authors.lastname: Morita
authors.affiliation: Acupuncture & Meridian Science Research Center, College of Oriental Medicine, Kyung Hee University, Seoul 130-701, Japan.
authors.forename: Dae Hyun
authors.initials: DH
authors.lastname: Hahm
authors.affiliation: Department of Science in Korean Medicine, Graduate School, College of Korean Medicine, Kyung Hee University, Seoul 130-701, Republic of Korea.
authors.forename: Insop
authors.initials: I
authors.lastname: Shim
authors.affiliation: Division of Bio-Imaging, Chuncheon Center, Korea Basic Science Institute, Chuncheon 200-701, Republic of Korea.
authors.forename: Song
authors.initials: S
authors.lastname: Her