背景：锁阳。在亚洲中药中长期以来被用作抗炎、抗抑郁和抗衰老药物。其乙酸乙酯提取物（ECS）已被确定为主要的抗氧化成分，具有神经保护和雌激素样作用。然而，ECS 在治疗抑郁症方面的潜力尚未得到探索。方法：我们在本研究中使用液相色谱-电喷雾串联质谱 (LC-MS/MS) 鉴定了 ECS 中的主要代谢物。使用网络分析来寻找与 ECS 抗神经炎症抑郁作用相关的潜在靶点和途径。此外，我们建立了皮质酮（CORT）诱导的抑郁小鼠模型，通过监测各种行为变化（例如蔗糖偏好、强迫游泳、悬尾和旷场试验）和海马生化指标来评估ECS的抗抑郁作用，以及验证网络分析结果。重要途径通过基于网络分析预测的蛋白质印迹进行验证。结果：我们的研究表明 ECS 具有显着的抗抑郁活性。 ECS 的 LC-MS/MS 分析鉴定出 30 种主要代谢物，包括根皮苷、根皮苷、熊果酸和柚皮素，以及其他黄酮类化合物、萜类化合物和酚酸。这些代谢物被发现与数据库中64个与神经炎症抑郁相关的候选靶蛋白相关，并通过过滤鉴定出10个中心蛋白：CXCL8、ICAM1、NOS2、SELP、TNF、IL6、APP、ACHE、MAOA和ADA。候选靶标的功能富集分析揭示了它们在调节细胞因子产生、炎症反应、细胞因子活性和肿瘤坏死因子受体结合中的主要作用。在体内，ECS 改善了小鼠模型的海马神经炎症。具体来说，ECS通过调节NF-κB-NLRP3炎症通路，减少海马炎症因子的表达，抑制M1小胶质细胞极化，缓解抑郁症。结论：基于实验和网络分析，本研究首次揭示ECS通过抗神经炎症发挥抗抑郁作用。我们的研究提供了关于使用 ECS 作为抑郁症替代治疗方法的宝贵信息。版权所有 © 2023 张、李、陈、胡、张、张和陆。

Background: Cynomorium songaricum Rupr. has long been used as an anti-inflammatory, antidepressant, and anti-aging agent in traditional Chinese medicine in Asia. Its ethyl acetate extract (ECS) has been identified as the main antioxidant component with neuroprotective and estrogen-like effects. However, the potential of ECS in treating depression has not been explored yet. Methods: We identified the primary metabolites in ECS in this study using liquid chromatography-electrospray tandem mass spectrometry (LC-MS/MS). Network analysis was used to find the potential targets and pathways associated with the anti-neuroinflammatory depression action of the ECS. In addition, we established a corticosterone (CORT)-induced depression mouse model to assess ECS's antidepressant effects by monitoring various behavioral changes (e.g., sucrose preference, forced swimming, tail suspension, and open field tests) and biochemical indices of the hippocampus, and validating the network analysis results. Significant pathways underwent verification through western blotting based on network analysis prediction. Results: Our study demonstrates that ECS possesses significant antidepressant activity. The LC-MS/MS analysis of ECS identified 30 main metabolites, including phloridzin, phlorizin, ursolic acid, and naringenin, as well as other flavonoids, terpenoids, and phenolic acids. These metabolites were found to be associated with 64 candidate target proteins related to neuroinflammatory depression from the database, and ten hub proteins were identified through filtration: CXCL8, ICAM1, NOS2, SELP, TNF, IL6, APP, ACHE, MAOA and ADA. Functional enrichment analyses of the candidate targets revealed their primary roles in regulating cytokine production, inflammatory response, cytokine activity, and tumor necrosis factor receptor binding. In vivo, ECS improved hippocampal neuroinflammation in the mouse model. Specifically, ECS reduced the expression of inflammatory factors in the hippocampus, inhibited M1 microglial cell polarization, and alleviated depression through the regulation of the NF-κB-NLRP3 inflammation pathway. Conclusion: Based on experimental and network analysis, this study revealed for the first time that ECS exerted antidepression effect via anti-neuroinflammation. Our research provides valuable information on the use of ECS as an alternative therapeutic approach for depression.Copyright © 2023 Zhang, Li, Chen, Hu, Zhang, Zhang and Lu.