Novel Antidepressant-Like Activity of Caffeic Acid Phenethyl
Ester is Mediated by Enhanced Glucocorticoid Receptor Function in the
Hippocampus
Evid Based Complement Alternat Med. 2014; 2014: 646039
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.
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