Bi Yu, Li Mengmeng, Wang Yue, Yao Junhan, Wang Yuxuan, Wang Siyi, Zhuang Leixin, Liu Shuang, Li Ziwei, Hao Zhichao, Guan Wei, Pan Juan, Jiang Peng, Zhang Yiqiang, Kuang Haixue, Chen Qingshan, Zhang Lili, Yang Bingyou, Liu Yan
Heilongjiang University of Chinese Medicine, Key Laboratory of Basic and Application Research of Beiyao (Heilongjiang University of Chinese Medicine), Ministry of Education, Traditional Chinese medicine (TCM) biological genetics (Heilongjiang province double first-class construction interdiscipline), Heilongjiang Touyan Innovation Team Program, 150040, China.
College of Agriculture, Northeast Agricultural University, Harbin 150030, China.
Phytomedicine. 2025 Jan;136:156240. doi: 10.1016/j.phymed.2024.156240. Epub 2024 Nov 19.
The major depressive disorder (MDD) is a heterogeneous condition and characterized by a high recurrence rate, with neuroinflammation playing a significant role in its various potential pathologies. In recent years, neuronal pyroptosis induced by neuroinflammation has garnered increasing attention in depression research. Bupleurum scorzonerifolium Willd. is depression research in traditional Chinese medicine prescriptions to treat depression and exhibits notable anti-inflammatory properties. Saikosaponins (SSs) are the primary active components of Bupleurum scorzonerifolium Willd., although their mechanism of action in relation to anti-depressive effects remains unclear.
The purpose is to evaluate the efficacy of Chinese herbal medicine in treating depression through the lens of modern pharmacology. Additionally, it aims to explore the potential value of new mechanisms in the treatment of depression.
An in vivo model of depression was established by intraperitoneal injection of LPS. HE staining, Nissl staining, and Golgi staining were used to evaluate the effectiveness of depression treatments in each group of mice. The activation of microglia was analyzed using immunofluorescence to evaluate the anti-inflammatory effects of drugs. In vitro models, N9 cells induced by LPS and ATP used CCK-8 assay, and lactate dehydrogenase assay were conducted to explore the therapeutic effect of the SSs. Western blot and immunohistochemical methods were employed to investigate the expression of P2X7 and apoptosis-related proteins. BzATP was introduced as a P2X7 agonist, and CETSA and CHX pulse-chase assay were utilized to verify the combined action and stability of the SSs with P2X7.
57 triterpenoid saponin compounds were identified by Unifi in Bupleurum scorzonerifolium Willd. In both in vivo and in vitro models, the SSs has been shown to significantly improve depression-like behavior, reduce central inflammation, and significantly inhibit neuronal pyroptosis in mice. The SSs can significantly decrease the expression of P2X7 in the brains of depressed mice and enhance the stability of P2X7 protein in N9 cells.
SSs in Bupleurum scorzonerifolium Willd. bind and inhibit the P2X7 receptor to alleviate neuronal pyroptosis and improve symptoms of depression.
重度抑郁症（MDD）是一种异质性疾病，具有高复发率的特点，神经炎症在其多种潜在病理过程中起重要作用。近年来，神经炎症诱导的神经元焦亡在抑郁症研究中受到越来越多的关注。柴胡是治疗抑郁症的中药方剂中的一味药材，具有显著的抗炎特性。柴胡皂苷（SSs）是柴胡的主要活性成分，但其抗抑郁作用的机制尚不清楚。
旨在从现代药理学角度评估中药治疗抑郁症的疗效。此外，还旨在探索抑郁症治疗新机制的潜在价值。
通过腹腔注射脂多糖建立抑郁症体内模型。采用苏木精-伊红（HE）染色、尼氏染色和高尔基染色评估每组小鼠抑郁症治疗的效果。利用免疫荧光分析小胶质细胞的激活情况，以评估药物的抗炎作用。在体外模型中，用脂多糖和三磷酸腺苷（ATP）诱导N9细胞，采用细胞计数试剂盒-8（CCK-8）法和乳酸脱氢酶测定法探索柴胡皂苷的治疗效果。采用蛋白质免疫印迹法和免疫组织化学方法研究P2X7和凋亡相关蛋白的表达。引入2’-(3’-氨基苯甲酰基)-ATP（BzATP）作为P2X7激动剂，并利用热蛋白质组分析（CETSA）和环己酰亚胺脉冲追踪试验验证柴胡皂苷与P2X7的联合作用和稳定性。
通过Unifi在柴胡中鉴定出57种三萜皂苷化合物。在体内和体外模型中，柴胡皂苷均显示出能显著改善抑郁样行为、减轻中枢炎症，并显著抑制小鼠神经元焦亡。柴胡皂苷可显著降低抑郁小鼠大脑中P2X7的表达，并增强N9细胞中P2X7蛋白的稳定性。
柴胡中的柴胡皂苷通过结合并抑制P2X7受体来减轻神经元焦亡，改善抑郁症症状。
