小檗碱通过限制 NF-κB 信号、氧化应激和神经炎症之间的自我延续性致病循环，减轻认知障碍并改善 tau 过度磷酸化。
Berberine attenuates cognitive impairment and ameliorates tau hyperphosphorylation by limiting the self-perpetuating pathogenic cycle between NF-κB signaling, oxidative stress and neuroinflammation.
机构信息
Department of Neurology, Renmin Hospital, Hubei University of Medicine, Shiyan Renmin Hospital, Shiyan, Hubei Province, China.
Department of Internal Medicine, Chongqing Prevention and Treatment Center for Occupational Diseases, Chongqing, China.
出版信息
Pharmacol Rep. 2017 Dec;69(6):1341-1348. doi: 10.1016/j.pharep.2017.06.006. Epub 2017 Jun 15.
BACKGROUND
Berberine (BBR) plays an important role in the prevention and treatment of Alzheimer's disease (AD). The present work was to explore whether BBR ameliorates cognitive deficits in AD and to investigate whether its underlying mechanism involves inhibiting hyperphosphorylated tau protein.
METHODS
The cognitive function was measured by the Morris water maze (MWM) test. The levels of hyperphosphorylated tau proteins were determined by Western blot. The biomarkers of NF-κB signaling pathway and oxidative stress were detected by Western blot and biochemical assays. The biomarkers of neuroinflammation were determined by Western blot and immunohistochemistry.
RESULTS
BBR improved learning and memory in APP/PS1 mice. BBR decreased the hyperphosphorylated tau protein in the hippocampus of APP/PS1 mice. BBR lowered the activity of NF-κB signaling in the hippocampus of AD mice. BBR-administration promoted the activity of glutathione (GSH) and inhibited lipid peroxidation in the hippocampus of AD mice.
CONCLUSION
BBR attenuated cognitive deficits and limited hyperphosphorylation of tau via inhibiting the activation of NF-κB signaling pathway, and by retarding oxidative stress and neuro-inflammation.
背景
小檗碱（BBR）在阿尔茨海默病（AD）的预防和治疗中起着重要作用。本研究旨在探讨 BBR 是否能改善 AD 患者的认知功能障碍，并研究其潜在机制是否涉及抑制过度磷酸化的 tau 蛋白。
方法
通过 Morris 水迷宫（MWM）测试测量认知功能。通过 Western blot 测定过度磷酸化 tau 蛋白的水平。通过 Western blot 和生化测定检测 NF-κB 信号通路和氧化应激的生物标志物。通过 Western blot 和免疫组化测定神经炎症的生物标志物。
结果
BBR 改善了 APP/PS1 小鼠的学习和记忆能力。BBR 降低了 APP/PS1 小鼠海马体中的过度磷酸化 tau 蛋白。BBR 降低了 AD 小鼠海马体中 NF-κB 信号通路的活性。BBR 给药促进了 AD 小鼠海马体中谷胱甘肽（GSH）的活性，并抑制了脂质过氧化。
结论
BBR 通过抑制 NF-κB 信号通路的激活，以及通过减缓氧化应激和神经炎症，减轻了认知功能障碍，并限制了 tau 的过度磷酸化。
Zotero 插件