Jujuboside A improves insomnia by maintaining mitochondrial homeostasis in prefrontal neurons

IF 3.5 3区医学 Q2 NEUROSCIENCES

Brain Research Bulletin Pub Date : 2025-05-05 DOI:10.1016/j.brainresbull.2025.111372

Zhen Zhang , Xinyue Che , Tingyu Feng , Juntao Zou , Guangpei Chen , Wenping Guo , Chunmei Ma , Haozhe Yuan , Jingying Chen , Xiaowu Xu

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引用次数: 0

Abstract

Objective

Jujuboside A (JB-A) is the major component of Semen Ziziphi Spinosae (SZS), a traditional Chinese herbal medicine used to treat sleep with clinical efficacy. This is the first study to investigate the effects of JB-A on mitochondrial structure and function in the prefrontal cortex of the insomnia model mice.

Methods

Young adult C57BL/6 mice were induced to develop insomnia by P-chlorophenylalanine. After 14 d of JB-A treatment via gavage, anxiety level was assessed using the open field and elevated plus maze tests. Next, the mitochondrial metabolic activity and morphological changes in the prefrontal cortex of each group of mice, as well as their effects on mitochondrial membrane potential, oxidative phosphorylation levels, and cytochrome c (Cyt c) content in neurons were measured.

Results

In our mouse model, JB-A ameliorated anxiety-like behaviors; up-regulated the membrane potential (Δψm) and had a therapeutic effect on the metabolic activity and damaged microscopic structure of mitochondria in the prefrontal cortex; effectively improved mitochondrial function by increasing the expression of Cyt c oxidase I and IV proteins, ATPase activity, and ATP content; and reduced the accumulation of Cyt c in the neuronal cytoplasm while inhibiting mitochondrial permeability transition pore (mPTP) opening.

Conclusions

JB-A can improve insomnia by restoring mitochondrial intracellular oxidative phosphorylation, regulating mPTP to maintain mitochondrial homeostasis, and alleviating structural damage, providing a scientific basis for finding new targets for insomnia treatment.

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红枣苷A通过维持前额叶神经元线粒体稳态改善失眠

目的研究酸枣皂苷A （JB-A）是治疗睡眠的中药，具有临床疗效。这是首次研究JB-A对失眠模型小鼠前额皮质线粒体结构和功能的影响。方法采用对氯苯丙氨酸诱导C57BL/6小鼠失眠。b - a灌胃治疗14 d后，采用开阔场和升高加迷宫测试评估焦虑水平。接下来，测量各组小鼠前额叶皮层线粒体代谢活性和形态变化，以及它们对线粒体膜电位、氧化磷酸化水平和神经元细胞色素c （Cyt c）含量的影响。结果在小鼠模型中，JB-A可改善焦虑样行为；上调膜电位（Δψm），对前额皮质线粒体代谢活性和微观结构损伤有治疗作用；通过提高Cyt c氧化酶I和IV蛋白的表达、ATP酶活性和ATP含量，有效改善线粒体功能；减少神经元细胞质中Cyt c的积累，同时抑制线粒体通透性过渡孔（mPTP）的开放。结论sjb - a可通过恢复线粒体胞内氧化磷酸化、调节mPTP维持线粒体稳态、减轻结构损伤等途径改善失眠，为寻找失眠治疗新靶点提供科学依据。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Brain Research Bulletin 医学-神经科学

CiteScore

6.90

自引率

2.60%

发文量

253

审稿时长

67 days

期刊介绍： The Brain Research Bulletin (BRB) aims to publish novel work that advances our knowledge of molecular and cellular mechanisms that underlie neural network properties associated with behavior, cognition and other brain functions during neurodevelopment and in the adult. Although clinical research is out of the Journal''s scope, the BRB also aims to publish translation research that provides insight into biological mechanisms and processes associated with neurodegeneration mechanisms, neurological diseases and neuropsychiatric disorders. The Journal is especially interested in research using novel methodologies, such as optogenetics, multielectrode array recordings and life imaging in wild-type and genetically-modified animal models, with the goal to advance our understanding of how neurons, glia and networks function in vivo.