Fang Yu, Li Yanqing, Wang Shumin, Deng Jie, Liang Jingtao, Li Siman, Yang Dongdong, Yan Bohua
Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China.
Chengdu University of Traditional Chinese Medicine / Affiliated Reproductive Maternity and Child Hospital, Chengdu, Sichuan, China.
Brain Res. 2025 Oct 1;1864:149780. doi: 10.1016/j.brainres.2025.149780. Epub 2025 Jun 11.
Depression is a common emotional disorder characterized by persistent low mood and decreased interest. Corydalis yanhusuo polysaccharides (CYP) are extracts from Corydalis yanhusuo, which have the effects of promoting blood circulation, relieving pain, anti-inflammation, and neuroprotection. This study investigates the effects and its underlying mechanisms of CYP in a chronic unpredictable mild stress (CUMS)-induced depression model using C57BL/6J mice. After 4 weeks of CYP treatment, the depressive behavior of mice was observed, and Nissl staining, H&E staining, and immunofluorescence were performed. The hypothalamic-pituitary-adrenal (HPA) axis factors levels were determined by enzyme-linked immunosorbent assay. Western blotting was used to detect protein expression. The results showed that CYP treatment improved depression-like behaviors in mice that received CUMS and ameliorated pathological damage the hippocampus and synaptic damage via regulating the expression of NeuN, SYP, and PSD95 proteins. CYP also reduced neuroinflammation by decreasing the expression of IL-1β, IL-18, NLRP3, and Caspase-1. In addition, CYP reduced adrenocorticotropic hormone (ACTH), corticotropin-releasing hormone (CRH), corticosterone (CORT), corticotropin releasing factor (CRF), mineralocorticoid receptor (MR) levels, and increased glucocorticoid receptor (GR) levels. Furthermore, CYP could regulate microglial activation and transform A1 astrocytes into neuroprotective A2 astrocytes, thereby mitigating neuronal damage by decreasing the expression of complement C3 (C3) and ionized calcium-binding adaptor molecule 1 (Iba-1), while increasing the expression of S100A10. However, CORT treatment significantly reversed above changes and aggravated depressive behavior in mice. In conclusion, CYP could improve CUMS-induced depression-like behaviors by regulating HPA axis-mediated microglial activation and inhibiting A1 transformation of astrocytes.
抑郁症是一种常见的情绪障碍，其特征为持续的情绪低落和兴趣减退。延胡索多糖（CYP）是从延胡索中提取的，具有促进血液循环、止痛、抗炎和神经保护作用。本研究使用C57BL/6J小鼠，在慢性不可预测轻度应激（CUMS）诱导的抑郁模型中研究CYP的作用及其潜在机制。CYP治疗4周后，观察小鼠的抑郁行为，并进行尼氏染色、苏木精-伊红染色和免疫荧光检测。采用酶联免疫吸附测定法测定下丘脑-垂体-肾上腺（HPA）轴因子水平。使用蛋白质免疫印迹法检测蛋白质表达。结果表明，CYP治疗改善了接受CUMS的小鼠的抑郁样行为，并通过调节NeuN、SYP和PSD95蛋白的表达减轻了海马体的病理损伤和突触损伤。CYP还通过降低IL-1β、IL-18、NLRP3和Caspase-1的表达减轻神经炎症。此外，CYP降低了促肾上腺皮质激素（ACTH）、促肾上腺皮质激素释放激素（CRH）、皮质酮（CORT）、促肾上腺皮质激素释放因子（CRF）、盐皮质激素受体（MR）水平，并增加了糖皮质激素受体（GR）水平。此外，CYP可调节小胶质细胞活化，并将A1星形胶质细胞转化为具有神经保护作用的A2星形胶质细胞，从而通过降低补体C3（C3）和离子钙结合衔接分子1（Iba-1）的表达，同时增加S100A10的表达来减轻神经元损伤。然而，CORT治疗显著逆转了上述变化，并加重了小鼠的抑郁行为。总之，CYP可通过调节HPA轴介导的小胶质细胞活化和抑制星形胶质细胞的A1转化来改善CUMS诱导的抑郁样行为。
