柴当博方乙酸乙酯组分改善CUMS小鼠海马神经可塑性：涉及糖皮质激素受体和Akt相关信号通路
Ethyl acetate fraction of Chaidangbo prescription (EAFC) improves hippocampal neural plasticity in CUMS mice: involving glucocorticoid receptors and Akt-related signaling pathway.
摘要(中文译文)
柴当堡方是通过拆方研究简化逍遥散（一种经典抗抑郁中药方剂）而衍生的抗抑郁中药方剂。尽管其展现出良好的抗抑郁疗效，但其物质基础和作用机制尚未阐明。本研究旨在明确EAFC增强CUMS小鼠海马神经可塑性的物质基础及作用机制。采用HPLC对EAFC中的活性成分进行定量分析。通过行为学测试评估CUMS小鼠的抑郁样行为，同时评价海马神经元形态、突触信号传导、凋亡及神经发生。整合非靶向代谢组学和网络药理学预测EAFC恢复抑郁症神经可塑性的机制，并对富集得到的靶点和通路进行验证。在体外研究中，采用CORT刺激的HT22细胞，结合MK-2206（Akt抑制剂）或ANA-12（TrkB抑制剂）处理，进一步证实EAFC的作用及机制。HPLC分析鉴定阿魏酸、柴胡皂苷A和迷迭香酸为EAFC的主要成分。EAFC显著减轻了包括快感缺失、行为绝望和探索减少在内的抑郁样行为；改善了小鼠海马突触结构和功能可塑性，维持了神经元完整性，并恢复了神经发生。此外，代谢组学鉴定出凋亡和mTOR信号传导的紊乱，网络药理学预测AKT1和NR3C1为关键靶点，PI3K/Akt通路为核心通路——这些发现随后通过Western blot得到验证。体外研究表明，EAFC减轻了HT22细胞的结构损伤和凋亡，同时增强了DCX表达。更重要的是，MK-2206而非ANA-12逆转了EAFC对GR核转位的影响，进一步研究发现EAFC增加了GR与Akt之间的结合。综上所述，EAFC通过激活TrkB/PI3K/Akt轴增强神经可塑性，以及独立地通过增加Akt-GR相互作用抑制GR核转位，从而缓解抑郁行为并恢复神经可塑性。这一双重机制揭示了神经营养系统与糖皮质激素系统之间一种新型的协调整合关系。
Abstract
The Chaidangbo prescription is an antidepressant traditional Chinese medicine (TCM) prescription derived by simplifying Xiaoyaosan (a classic antidepressant TCM prescription) through dismantling research. While it shows promising antidepressant efficacy, its material basis and mechanism remain unelucidated. This study sought to identify the material basis and mechanisms by which EAFC enhances hippocampal neuroplasticity in CUMS mice. The active ingredients in EAFC were quantified using HPLC. Depressive-like behaviors in CUMS mice were assessed behavioral test, alongside evaluation of hippocampal neuronal morphology, synaptic signaling, apoptosis, and neurogenesis. Integrated non-targeted metabolomics and network pharmacology predicted EAFC's mechanisms for restoring neuroplasticity in depression, with enrichment-derived targets and pathways validated. In vitro studies on CORT-stimulated HT22 cells, combined with MK-2206 (Akt inhibitor) or ANA-12 (TrkB inhibitor) treatment, further confirmed EAFC's effects and mechanisms. HPLC analysis identified ferulic acid, saikosaponin A, and rosmarinic acid as the main constituents of EAFC. EAFC significantly attenuated depression-like behaviors including anhedonia, behavioral despair and reduced exploration; improved synaptic structure and functional plasticity in the mouse hippocampus, maintained neuronal integrity, and restored neurogenesis. Furthermore, metabolomics identified disturbances in apoptosis and mTOR signaling, while network pharmacology predicted AKT1 and NR3C1 as key targets, with the PI3K/Akt pathway as a hub-findings which were subsequently validated by Western blot. In vitro research demonstrated that EAFC reduced structural damage and apoptosis in HT22 cells while enhancing DCX expression. More importantly, MK-2206 but not ANA-12 reversed the effect of EAFC on GR nuclear translocation, and further findings revealed that EAFC increases the binding between GR and Akt. In summary, EAFC alleviates depressive behaviors and restores neuroplasticity by activating the TrkB/PI3K/Akt axis to enhance neuroplasticity, and independently, by increasing Akt-GR interaction to restrain GR nuclear translocation. This dual mechanism highlights a novel coordinated integration between neurotrophic and glucocorticoid systems.
如何引用
AMA
Jiuseng Zeng, Yu Tang, Aotao Zhao, Jincheng Yang, Xiongwei Zhang, Hu Qi, et al. Ethyl acetate fraction of Chaidangbo prescription (EAFC) improves hippocampal neural plasticity in CUMS mice: involving glucocorticoid receptors and Akt-related signaling pathway.. Phytomedicine : international journal of phytotherapy and phytopharmacology. 2026; doi:10.1016/j.phymed.2026.158411.
APA
Jiuseng Zeng, Yu Tang, Aotao Zhao, Jincheng Yang, Xiongwei Zhang, Hu Qi, et al (2026). Ethyl acetate fraction of Chaidangbo prescription (EAFC) improves hippocampal neural plasticity in CUMS mice: involving glucocorticoid receptors and Akt-related signaling pathway.. Phytomedicine : international journal of phytotherapy and phytopharmacology. https://doi.org/10.1016/j.phymed.2026.158411
GB/T 7714
Jiuseng Zeng, Yu Tang, Aotao Zhao, Jincheng Yang, Xiongwei Zhang, Hu Qi, et al. Ethyl acetate fraction of Chaidangbo prescription (EAFC) improves hippocampal neural plasticity in CUMS mice: involving glucocorticoid receptors and Akt-related signaling pathway.[J]. Phytomedicine : international journal of phytotherapy and phytopharmacology, 2026 doi:10.1016/j.phymed.2026.158411.
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