Gelsemine, a natural alkaloid extracted from Gelsemium elegans Benth. alleviates neuroinflammation and cognitive impairments in Aβ oligomer-treated mice
Gelsemine, a natural alkaloid extracted from Gelsemium elegans Benth. alleviates neuroinflammation and cognitive impairments in Aβ oligomer-treated mice
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钩吻碱是从钩吻花中提取的天然生物碱。
DOI：
10.1007/s00213-020-05522-y
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发表时间：
2020-05-04
影响因子：
3.4
通讯作者：
Xian，Yan-Fang
中科院分区：
文献类型：
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作者：
Chen，Liping;Pan，Hanbo;Xian，Yan-Fang
钩吻碱是从钩吻中提取的一种天然生物碱，钩吻碱是一种传统的中草药。钩吻碱已被证明能渗透大脑，并能产生神经活性，如抗焦虑和缓解神经痛的作用，这表明这种天然化合物可能用于治疗神经系统疾病。本研究首次发现，低浓度（5-10 μg/kg）钩吻素能显著减轻阿尔茨海默病（AD）主要神经毒素β-淀粉样蛋白（Aβ）寡聚体所致的认知功能损害。此外，钩吻素可显著抑制Aβ寡聚体诱导的小胶质细胞和星形胶质细胞过度活化，表明钩吻素可减少AD相关的神经胶质增生。结论：钩吻素可抑制小鼠脑内促炎细胞因子白细胞介素1β（IL-1β）、白细胞介素6（IL-6）和肿瘤坏死因子α（TNF-α）的过度表达。Western blotting结果显示，钩吻碱可显著增加pSer 9-糖原合成酶激酶3β（GSK 3 β）的表达，降低tau蛋白的过度磷酸化。此外，钩吻素阻止Aβ寡聚体诱导的PSD-95（一种代表性突触后蛋白）减少。所有这些结果直接证明了钩吻素的抗A β寡聚体神经保护特性，为开发基于钩吻素的治疗Aβ相关神经变性疾病（特别是AD）的药物开辟了新的视角。
Gelsemine is a natural alkaloid extracted from Gelsemium elegans Benth., a traditional Chinese medicinal herb. Gelsemine has been shown to penetrate the brain, and could produce neurological activities, such as anxiolytic and neuralgia-alleviating effects, suggesting that this natural compound might be used for treating nervous system diseases. In this study, we have found, for the first time, that gelsemine at low concentrations (5–10 μg/kg) significantly alleviated cognitive impairments induced by β-amyloid (Aβ) oligomer, a main neurotoxin of Alzheimer’s disease (AD). In addition, gelsemine substantially prevented Aβ oligomer-induced over-activation of microglia and astrocytes, indicating that gelsemine might reduce AD-related gliosis. Consistently, gelsemine inhibited the over-expression of pro-inflammatory cytokines, including interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α), in the brain of mice. Moreover, gelsemine largely increased the expression of pSer9-glycogen synthase kinase-3β (GSK3β), and decreased the hyper-phosphorylation of tau protein as evidenced by Western blotting analysis. Furthermore, gelsemine prevented Aβ oligomer-induced reduction of PSD-95, a representative post-synaptic protein. All these results directly demonstrated the anti-Aβ oligomer neuroprotective properties of gelsemine, opening a novel perspective for the development of gelsemine-based therapeutics against Aβ-associated neurodegeneration disorders, including AD in particular.