Related Experiment Video
Updated: Apr 19, 2026

Network Pharmacology and Validation of the Antidepressant Mechanisms of Qiangzhifang in a Chronic Restraint Stress-induced Depression Rat Model
Published on: June 6, 2025
Novel antidepressant-like activity of caffeic Acid phenethyl ester is mediated by enhanced glucocorticoid receptor
Mi-Sook Lee1, Young Han Kim2, Bo-Ram Lee2
1Division 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.
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.
More Related Videos
Related Concept Videos
Antidepressant Drugs: MAOIs and Other Agents
Adrenergic Agonists: Indirect-Acting Agents
One mechanism involves depleting stored catecholamines by displacing them from synaptic vesicles. These agents, known as "displacers," are transported into vesicles at the expense of noradrenaline. Examples include amphetamine and tyramine, which lack a catechol moiety, resulting in prolonged action, improved oral...
Antidepressant Drugs: Overview
Cognitive Enhancers: Cholinesterase Inhibitors and NMDA Receptor Antagonists
Antidepressant Drugs: Tricyclics, SSRIs, and SNRIs
Drug Abuse and Addiction: Pharmacological Phenomena

