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.

IF 8.5 1区 农林科学 Q1 CHEMISTRY, APPLIED Food Chemistry Pub Date : 2025-01-15 Epub Date: 2024-09-18 DOI:10.1016/j.foodchem.2024.141328
Meng-Ling Zhang, Xiao-Peng Li, Li-Fang Gao, Jian Liu, Zi-Jun Bi, Yu-Han Miao, Yang Shan, Huan-Ling Yu
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Abstract

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.

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Nobiletin是丙酮酸激酶同工酶M1/M2蛋白的激活剂,它能上调糖酵解信号通路,缓解斑马鱼夜间因人工光照而产生的类似抑郁的行为。
我们建立了一个斑马鱼模型,通过夜间暴露于人造光(ALAN)诱导抑郁样行为,并发现金霉素(NOB)能缓解抑郁样行为。随后,根据24小时自由活动试验、时钟基因表达和脑组织转录组测序的结果,确定糖酵解信号通路是NOB发挥抗抑郁作用的潜在靶点。利用 ALAN 斑马鱼模型,我们发现补充外源 L-乳酸可减轻抑郁样行为。分子对接和分子动力学模拟揭示了 NOB 与丙酮酸激酶同工酶 M1/M2(PKM2)蛋白之间的分子间相互作用。然后,我们用化合物 3 k 构建了一个斑马鱼模型,在该模型中,PKM2 受到抑制。我们对该模型的分析表明,NOB 可通过抑制 PKM2 来缓解抑郁样行为。总之,NOB 通过靶向 PKM2 和激活糖酵解信号通路,减轻了 ALAN 诱导的斑马鱼抑郁样行为。
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来源期刊
Food Chemistry
Food Chemistry 工程技术-食品科技
CiteScore
16.30
自引率
10.20%
发文量
3130
审稿时长
122 days
期刊介绍: Food Chemistry publishes original research papers dealing with the advancement of the chemistry and biochemistry of foods or the analytical methods/ approach used. All papers should focus on the novelty of the research carried out.
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