Tan Lin, Li Jiayue, Sun Dingcheng, Tian Xinyi, Zhong Xiaoli, Shan Yiyi
Department of Urology Surgery and Department of Nursing, People's Hospital of Deyang City, Deyang, Sichuan, China.
College of Food Science, Northeast Agricultural University, Haerbin, China.
Front Pharmacol. 2025 May 16;16:1585290. doi: 10.3389/fphar.2025.1585290. eCollection 2025.
Natural plant-derived active ingredients have gained increasing attention for their potential in the treatment of depression due to their safety and multi-target pharmacological activities. Saikosaponin A (SSA), a major bioactive saponin extracted from (a medicine and food homologous plant), has been reported to possess anti-inflammatory, neuroprotective, and antioxidative properties. In this study, we evaluated the antidepressant-like effects of SSA in a mouse model of chronic unpredictable mild stress (CUMS)-induced depression. Mice were subjected to CUMS, followed by daily administration of SSA (20 mg/kg, po for 6 weeks). Behavioral tests, including tail suspension test, open field test, elevated plus maze, and marble burying test, indicated that SSA significantly alleviated depressive-like and anxiety-like behaviors. Histopathological analysis by H&E staining showed that SSA reduced hippocampal neuronal damage induced by chronic stress. Biochemical assays revealed that SSA normalized levels of neurotransmitters (5-HT, DA, and 5-HIAA), enhanced antioxidant enzyme activity (SOD, CAT, and GSH), and suppressed neuroinflammatory cytokine production (TNF-α, IL-1β, and IL-6). Mechanistically, SSA exerted its antidepressant effects by inhibiting the TLR4/NF-κB signaling pathway and upregulating BDNF expression. In PC12 cells, TLR4 overexpression attenuated SSA's protective effects, whereas TLR4 silencing enhanced cellular resistance to corticosterone-induced damage. These findings suggest SSA alleviates CUMS-induced depression-like behaviors in mice by modulating neuroinflammation and oxidative stress through the TLR4/NF-κB/BDNF signaling axis, indicating its potential as a functional food-derived therapy for depression.
天然植物来源的活性成分因其安全性和多靶点药理活性，在抑郁症治疗中的潜力日益受到关注。柴胡皂苷A（SSA）是从一种药食同源植物中提取的主要生物活性皂苷，据报道具有抗炎、神经保护和抗氧化特性。在本研究中，我们评估了SSA在慢性不可预测轻度应激（CUMS）诱导的小鼠抑郁模型中的抗抑郁样作用。小鼠接受CUMS处理，随后每天给予SSA（20mg/kg，口服，持续6周）。行为学测试，包括悬尾试验、旷场试验、高架十字迷宫试验和大理石埋藏试验，表明SSA显著减轻了抑郁样和焦虑样行为。苏木精-伊红（H&E）染色的组织病理学分析表明，SSA减少了慢性应激诱导的海马神经元损伤。生化分析显示，SSA使神经递质（5-羟色胺、多巴胺和5-羟吲哚乙酸）水平正常化，增强了抗氧化酶活性（超氧化物歧化酶、过氧化氢酶和谷胱甘肽），并抑制了神经炎症细胞因子的产生（肿瘤坏死因子-α、白细胞介素-1β和白细胞介素-6）。机制上，SSA通过抑制Toll样受体4（TLR4）/核因子κB（NF-κB）信号通路并上调脑源性神经营养因子（BDNF）表达发挥其抗抑郁作用。在PC12细胞中，TLR4过表达减弱了SSA的保护作用，而TLR4沉默增强了细胞对皮质酮诱导损伤的抗性。这些发现表明，SSA通过TLR4/NF-κB/BDNF信号轴调节神经炎症和氧化应激来减轻CUMS诱导的小鼠抑郁样行为，表明其作为抑郁症功能性食品疗法的潜力。
