Gelsemine, a natural alkaloid extracted from Gelsemium elegans Benth. alleviates neuroinflammation and cognitive impairments in Aβ oligomer-treated mice

Introduction 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. Results In this study, we have found, for the first time, that gelsemine at low concentrations (5-10 mu g/kg) significantly alleviated cognitive impairments induced by beta-amyloid (A beta) oligomer, a main neurotoxin of Alzheimer's disease (AD). In addition, gelsemine substantially prevented A beta 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-1 beta (IL-1 beta), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha), in the brain of mice. Moreover, gelsemine largely increased the expression of pSer9-glycogen synthase kinase-3 beta (GSK3 beta), and decreased the hyper-phosphorylation of tau protein as evidenced by Western blotting analysis. Furthermore, gelsemine prevented A beta oligomer-induced reduction of PSD-95, a representative post-synaptic protein. Conclusion All these results directly demonstrated the anti-A beta oligomer neuroprotective properties of gelsemine, opening a novel perspective for the development of gelsemine-based therapeutics against A beta-associated neurodegeneration disorders, including AD in particular.