Page 323 - 2025中醫藥與天然藥物聯合學術研討會-中醫藥與天然藥物的挑戰Ｘ機遇與未來大會手冊

TC-08

Antidepressant-like effect of hispidin involves activation of BDNF signaling

in mice

1
2
2
Yen-Yu Kuo, Han‑Wen Chuang, Chih-Chia Huang, 3,4 Kuang-Ti Chen, Mang-Hung
,2
2
Tsai, Cheng-Han Lin, I‑Hua Wei*
2

1 School of Graduate Institute of Biomedical Sciences, China Medical University, Taichung
404328, Taiwan
2 Department of Anatomy, China Medical University, Taichung 404328, Taiwan
3 Tsaotun Psychiatric Center, Ministry of Health and Welfare, Nantou 54249, Taiwan
4 Program in Translational Medicine, National Chung Hsing University, Taichung 402202,
Taiwan
* E-mail: ihwei@mail.cmu.edu.tw

Abstract
Depressive disorders are among the most prevalent psychiatric illnesses worldwide and are
ranked by the World Health Organization as one of the top three global diseases. Conventional
antidepressants remain clinically limited by their slow onset of action, particularly in high-risk
suicidal populations and patients with severe major depressive disorder. Ketamine, a fast-acting
antidepressant, exerts effects through N-methyl-D-aspartate receptor (NMDAR) antagonism,
which enhances glutamatergic transmission, activates AMPA receptors (AMPAR), and triggers
downstream mammalian target of rapamycin (mTOR) and brain-derived neurotrophic factor
(BDNF) signaling. However, adverse effects and abuse potential restrict its clinical utility,
underscoring the need for safer alternatives. Hispidin, a phenolic compound derived from
Phellinus linteus and widely used in traditional Asian medicine, has been reported to exhibit
antioxidant, anticancer, and neuroprotective properties. In this study, we examined the
antidepressant-like potential of hispidin in a mouse model of depression, referencing ketamine’s
rapid mechanism of action. We specifically investigated whether hispidin activates protein
kinase B (AKT)–glycogen synthase kinase-3β (GSK3β) and extracellular signal-regulated
kinase (ERK) signaling to mediate similar behavioral and molecular outcomes. Behaviorally,
hispidin significantly reduced immobility in the forced swim test (FST) without affecting
locomotor activity in the open field test (OFT). Molecular analyses of hippocampal tissue
revealed enhanced phosphorylation of ERK, AKT, GSK3β, AMPAR GluA1 (Ser831/Ser845),
and mTOR, alongside upregulated BDNF expression. Overall, these findings demonstrate that
hispidin exerts rapid antidepressant-like actions via ERK/AKT–GSK3β mediated AMPAR–
mTOR signaling and BDNF upregulation, supporting its potential as a novel antidepressant
candidate.

Keywords: Depressive disorders; Ketamine; Antidepressant; Hispidin; BDNF