Cao Min-Min, Guo Zhe, Wang Jun, Ma Hui-Yong, Qin Xiao-Yan, Hu Yang, Lan Rongfeng
Key Laboratory of Ecology and Environment in Minority Areas National Ethnic Affairs Commission, Center on Translational Neuroscience, College of Life and Environmental Sciences, Minzu University of China, Beijing, 100081, China.
The Emergency Department, The Third Affiliated Hospital of Guangxi Medical University, Nanning, 530021, China.
Free Radic Biol Med. 2025 May;232:340-352. doi: 10.1016/j.freeradbiomed.2025.03.014. Epub 2025 Mar 13.
Astragalin (AST) is a flavonoid glycoside commonly found in edible plants and medicinal herbs with a variety of therapeutic effects. This study aimed to investigate whether AST protects the integrity of the blood-brain barrier (BBB) and inhibits neuroinflammation, thereby alleviating depressive-like behaviors. LPS-stimulated cultured cells and LPS-induced BBB disruption and depressive-like behavior mice models were employed. We founded that AST inhibited LPS-induced inflammatory responses in microglial BV2 cells and protected SH-SY5Y cells from inflammatory injury. In mice, AST effectively ameliorated LPS-induced depressive-like behaviors, which was attributed to its ability to maintain BBB integrity and inhibit inflammatory damage caused by LPS invasion. Furthermore, AST suppressed LPS-induced activation of glial cells, protecting neuronal dendritic spines, synapses, and mitochondria from inflammatory damage. It also reduced the elevation of pro-inflammatory factors such as TNF-α, IL-1β, and IL-6, and normalized the aberrant activation of inflammatory signaling pathways, including RIPK1/RIPK3/MLKL and mTOR/NF-κB. In conclusion, AST protects BBB integrity and brain tissue from inflammatory damage, offering new insights for drug development and clinical interventions in systemic inflammatory responses, such as sepsis-induced encephalitis.
黄芪苷（AST）是一种常见于可食用植物和药草中的黄酮糖苷，具有多种治疗作用。本研究旨在探讨AST是否能保护血脑屏障（BBB）的完整性并抑制神经炎症，从而减轻抑郁样行为。采用了脂多糖（LPS）刺激的培养细胞以及LPS诱导的BBB破坏和抑郁样行为小鼠模型。我们发现，AST可抑制小胶质细胞BV2中LPS诱导的炎症反应，并保护SH-SY5Y细胞免受炎症损伤。在小鼠中，AST有效改善了LPS诱导的抑郁样行为，这归因于其维持BBB完整性以及抑制LPS侵袭所致炎症损伤的能力。此外，AST抑制了LPS诱导的胶质细胞活化，保护神经元树突棘、突触和线粒体免受炎症损伤。它还降低了促炎因子如肿瘤坏死因子-α、白细胞介素-1β和白细胞介素-6的升高，并使包括RIPK1/RIPK3/MLKL和mTOR/核因子-κB在内的炎症信号通路的异常激活恢复正常。总之，AST保护BBB完整性和脑组织免受炎症损伤，为全身炎症反应（如脓毒症诱导的脑炎）的药物开发和临床干预提供了新的见解。
