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Phytomedicine, Available online 30 January 2026, 157906 | https://doi.org/10.1016/j.phymed.2026.157906 Dieckol, a phlorotannin from Ecklonia cava, alleviates stress hormone-induced depressive-like behaviors through glucocorticoid receptor antagonism

Inhye Park ^a,b#, Jung-Eun Lee ^a#, Minji Kim ^a,b#, Minseok Yoon ^a, Min Jung Kim ^a,b, Min-Sun Kim ^c, Suengmok Cho ^d, Min Young Um ^a,b*

^aFood Functionality Research Division, Korea Food Research Institute, Wanju 55365, Republic of Korea
^bDepartment of Food Biotechnology, University of Science and Technology, Daejeon 34113, Republic of Korea
^cFood Analysis Research Center, Korea Food Research Institute, Wanju 55365, Republic of Korea
^dDepartment of Food Science and Technology, Institute of Food Science, Pukyong National University, Busan 48513, Republic of Korea.

^#These contributed equally to this work.
^*Corresponding author: Min Young Um

Abstract

Background
Depression imposes significant social, economic, and health burdens worldwide. Although phlorotannin-rich extract from Ecklonia cava (PS) and its active compound dieckol (DK) exhibit various biological activities, their antidepressant- and anxiolytic-like effects and underlying mechanisms remain unclear.

Purpose
This study investigated the antidepressant- and anxiolytic-like potential of PS and DK in a corticosterone (CORT)-induced mouse model of depression and anxiety, focusing on glucocorticoid receptor (GR) signaling.
Methods
CORT-treated mice were orally administered PS or DK, and behavioral tests were performed to assess depressive- and anxiety-like behaviors. PS composition was analyzed using LC-MS/MS. Molecular docking predicted the binding of PS components to GR. GR nuclear translocation, target gene expression, and downstream signaling were examined using behavioral, molecular, and computational approaches.

Results
PS alleviated CORT-induced depressive- and anxiety-like behaviors, accompanied by reduced GR nuclear translocation, suppression of Mkp-1, and restoration of ERK–CREB–BDNF signaling. Molecular docking analysis predicted strong binding of DK to the GR ligand-binding domain. Consistently, DK reduced GR nuclear translocation and GRE binding, downregulated GR target genes (Mkp-1, Sgk-1, Fkbp5, and Bdnf), and restored ERK-CREB-BDNF signaling. In vivo, DK also improved CORT-induced behavioral deficits and normalized HPA axis activity and neurotransmitter levels.

Conclusion
Collectively, our results suggest that DK, a major bioactive phlorotannin from E. cava, exerts antidepressant- and anxiolytic-like effects in association with modulation antagonism of GR signaling, highlighting its therapeutic potential as a natural GR-modulating agent for stress-related mood disorders.

논문소개전체 설명

Dieckol은 Ecklonia cava(감태)의 대표적인 폴리페놀(phlorotannin)로, 스트레스 호르몬인 corticosterone으로 유도된 우울·불안 유사 행동 생쥐 모델에서 항우울 및 항불안 효과를 나타냄. Dieckol은 glucocorticoid receptor(GR)의 핵 이동 및 타깃 유전자 발현을 억제하고, 시상하부–뇌하수체–부신(HPA) 축 기능과 신경전달물질 수준을 정상화함으로써 GR 신호의 과활성을 조절하는 것으로 확인됨. 이러한 결과는 dieckol이 스트레스 관련 기분장애에 대한 자연 유래 GR 조절제로서 치료적 잠재력을 지님을 시사함

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