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International Journal of Clinical and Experimental Medicine Research

ISSN Online: 2575-7970 ISSN Print: 2575-7989 CODEN: IJCEMH
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ArticleOpen Access http://dx.doi.org/10.26855/ijcemr.2026.07.015

Mechanistic Study of Curcumin Ameliorating Manic-like Behaviors in a Bipolar Disorder-like Mouse Model Associated with GPX4/ACSL4-related Ferroptosis Inhibition

Shuhan Jing1, Jun Zhou2,*

1Shanghai Pinghe Bilingual School, Shanghai 201206, China.

2Wuhan Jingkai Foreign Language School, Wuhan 430118, Hubei, China.

*Corresponding author: Jun Zhou

Published: July 31, 2026

Abstract

Bipolar disorder (BD) has limited proven treatments, and pharmacotherapy in adolescents raises significant safety concerns due to adverse effects such as renal toxicity, thyroid dysfunction, and mood switching. Curcumin, the principal polyphenolic constituent of Curcuma longa, has emerged as a promising alternative therapeutic intervention, yet its underlying biological mechanisms in BD remain largely unexplored. In this study, a bipolar disorder-like (BD-like) mouse model was established using an amphetamine-induced hyperlocomotion paradigm combined with chronic unpredictable mild stress (CUMS) to examine whether curcumin exerts therapeutic effects through the modulation of GPX4/ACSL4-mediated ferroptosis. Behavioral assessments showed that curcumin alleviated manic-like hyperlocomotion, reduced anxiety-like behaviors, and improved cognitive performance. BD-like model mice showed ferroptosis-related alterations in the hippocampus, marked by iron accumulation, elevated malondialdehyde, reduced GPX4, and increased ACSL4. Curcumin attenuated these alterations, whereas erastin, a ferroptosis inducer, counteracted both the behavioral and molecular benefits. These findings indicate that curcumin alleviates BD-like behaviors in association with the suppression of ferroptosis-related alterations, supporting the involvement of the GPX4/ACSL4 axis and suggesting a mechanistic link with iron-dependent neuronal vulnerability and positioning curcumin as a potential adjunctive therapy for bipolar disorder.

Keyword

Bipolar disorder; curcumin; ferroptosis; GPX4; ACSL4; manic-like behavior

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Copyright

© 2026 by the author(s).
This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution-NonCommercial-NoDerivatives (CC BY-NC-ND) license, which permits non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited and is not modified or adapted.
https://creativecommons.org/licenses/by-nc-nd/4.0/

How to cite this paper

Mechanistic Study of Curcumin Ameliorating Manic-like Behaviors in a Bipolar Disorder-like Mouse Model Associated with GPX4/ACSL4-related Ferroptosis Inhibition

How to cite this paper: Shuhan Jing, Jun Zhou. (2026) Mechanistic Study of Curcumin Ameliorating Manic-like Behaviors in a Bipolar Disorder-like Mouse Model Associated with GPX4/ACSL4-related Ferroptosis Inhibition. International Journal of Clinical and Experimental Medicine Research10(4), 334-343.

DOI: http://dx.doi.org/10.26855/ijcemr.2026.07.015