Chai Wen, Zhang Ji, Xiang Zhengbing, Zhang Honglian, Mei Zhujun, Nie Hongbing, Xu Renxu, Zhang Ping
Department of Neurology, The First Affiliated Hospital of Nanchang Medical College/Jaingxi Provincial People's Hospital, No.152, Aiguo Road, 330006, Nanchang, Jiangxi, P.R. China.
Department of General Practice/General Family Medicine, The First Affiliated Hospital of Nanchang Medical College/Jaingxi Provincial People's Hospital, 330006, Nanchang, Jiangxi, P.R. China.
Metab Brain Dis. 2022 Apr;37(4):1145-1154. doi: 10.1007/s11011-022-00932-7. Epub 2022 Mar 10.
This study aimed to explore the mechanism of Nobiletin attenuating Alzheimer's disease (AD) by inhibiting neuroinflammation.
The expression of inflammatory cytokines and HMGB-1 in serum of AD patients were examined. Microglia (MGs) were treated with different doses of Nobiletin before LPS and Nigericin induction. Cell viability and apoptosis were determined by CCK-8 and TUNEL assays, respectively. APP/PS1 mice were gavaged with Nobiletin, and Morris water maze (MWM) was established to record swimming speed, escape latency, the number of platform crossings, and time spent in the platform quadrant. MGs activation in brain tissues was evaluated by immunofluorescence. The expression of pyroptosis-related proteins, inflammatory cytokines, and HMGB-1 was determined in the hippocampus and MGs.
The levels of inflammatory cytokines and HMGB-1 were high in serum of AD patients. Treatment with different concentrations of Nobiletin prominently enhanced cell viability and reduced apoptosis and the expression of inflammatory cytokine and pyroptosis-related proteins in LPS + Nigericin-induced MGs. Gavage of different doses of Nobiletin into APP/PS1 mice shortened the escape latency in mice, diminished MGs activation in brain tissues, and remarkably elevated the number of platform crossings and the time spent in the platform quadrant without obvious change in swimming speed, suggesting that Nobiletin improved the spatial learning and memory abilities in APP/PS1 mice. The expression of pyroptosis-related proteins, HMGB-1, and inflammatory cytokines was decreased dramatically by Nobiletin in the hippocampus of APP/PS1 mice.
Nobiletin can inhibit neuroinflammation by inhibiting HMGB-1, pyroptosis-related proteins, and inflammatory cytokines, thus mitigating AD.
本研究旨在探讨诺比列汀通过抑制神经炎症减轻阿尔茨海默病（AD）的机制。
检测AD患者血清中炎性细胞因子和高迁移率族蛋白B1（HMGB-1）的表达。在脂多糖（LPS）和尼日利亚菌素诱导前，用不同剂量的诺比列汀处理小胶质细胞（MGs）。分别通过CCK-8法和TUNEL法测定细胞活力和凋亡情况。给APP/PS1小鼠灌胃诺比列汀，建立莫里斯水迷宫（MWM）以记录游泳速度、逃避潜伏期、穿越平台次数和在平台象限停留的时间。通过免疫荧光评估脑组织中MGs的激活情况。测定海马体和MGs中焦亡相关蛋白、炎性细胞因子和HMGB-1的表达。
AD患者血清中炎性细胞因子和HMGB-1水平较高。用不同浓度的诺比列汀处理可显著提高LPS + 尼日利亚菌素诱导的MGs的细胞活力，降低凋亡以及炎性细胞因子和焦亡相关蛋白的表达。给APP/PS1小鼠灌胃不同剂量的诺比列汀可缩短小鼠的逃避潜伏期，减少脑组织中MGs的激活，并显著提高穿越平台次数和在平台象限停留的时间，而游泳速度无明显变化，这表明诺比列汀改善了APP/PS1小鼠的空间学习和记忆能力。诺比列汀可显著降低APP/PS1小鼠海马体中焦亡相关蛋白、HMGB-1和炎性细胞因子的表达。
诺比列汀可通过抑制HMGB-1、焦亡相关蛋白和炎性细胞因子来抑制神经炎症，从而减轻AD。
