Nobiletin, an activator of the pyruvate kinase isozyme M1/M2 protein, upregulated the glycolytic signalling pathway and alleviated depressive-like behaviour caused by artificial light exposure at night in zebrafish.

Autor: Zhang ML; School of Public Health, Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing 100069, China; Institute of Chemicals Safety, Chinese Academy of Inspection and Quarantine, Beijing 100176, China., Li XP; Hunan Agricultural Product Processing Institute, Hunan Academy of Agricultural Sciences, Hunan Provincial Key Laboratory for Fruits and Vegetables Storage Processing and Quality Safety, Changsha 410000, China., Gao LF; School of Public Health, Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing 100069, China., Liu J; Hunan Agricultural Product Processing Institute, Hunan Academy of Agricultural Sciences, Hunan Provincial Key Laboratory for Fruits and Vegetables Storage Processing and Quality Safety, Changsha 410000, China., Bi ZJ; School of Public Health, Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing 100069, China., Miao YH; School of Public Health, Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing 100069, China., Shan Y; Hunan Agricultural Product Processing Institute, Hunan Academy of Agricultural Sciences, Hunan Provincial Key Laboratory for Fruits and Vegetables Storage Processing and Quality Safety, Changsha 410000, China., Yu HL; School of Public Health, Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing 100069, China. Electronic address: yuhlzjl@ccmu.edu.cn.
Jazyk: angličtina
Zdroj: Food chemistry [Food Chem] 2025 Jan 15; Vol. 463 (Pt 2), pp. 141328. Date of Electronic Publication: 2024 Sep 18.
DOI: 10.1016/j.foodchem.2024.141328
Abstrakt: We established a zebrafish model of depression-like behaviour induced by exposure to artificial light at night (ALAN) and found that nobiletin (NOB) alleviated depression-like behaviour. Subsequently, based on the results of a 24-h free movement assay, clock gene expression and brain tissue transcriptome sequencing, the glycolysis signalling pathway was identified as a potential target through which NOB exerted antidepressant effects. Using the ALAN zebrafish model, we found that supplementation with exogenous L-lactic acid alleviated depressive-like behaviour. Molecular docking and molecular dynamics simulations revealed an inter-molecular interaction between NOB and the pyruvate kinase isozyme M1/M2 (PKM2) protein. We then used compound 3 k to construct a zebrafish model in which PKM2 was inhibited. Our analysis of this model suggested that NOB alleviated depression-like behaviour via inhibition of PKM2. In summary, NOB alleviated depressive-like behaviour induced by ALAN in zebrafish via targeting of PKM2 and activation of the glycolytic signalling pathway.
Competing Interests: Declaration of competing interest The authors declare no conflict of interest. This work has not been submitted/published or being submitted to another journal.
(Copyright © 2024 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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