Liping Chen1, Hanbo Pan1, Yujing Bai1, Huiqin Li2, Wen Yang2, Zhi-Xiu Lin2,3,4, Wei Cui5,6, Yan-Fang Xian7,8. 1. Ningbo Key Laboratory of Behavioral Neuroscience, Zhejiang Provincial Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, Ningbo, People's Republic of China. 2. School of Chinese Medicine, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, SAR, People's Republic of China. 3. Brain Research Centre, School of Chinese Medicine, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, SAR, People's Republic of China. 4. Hong Kong Institute of Integrative Medicine, The Chinese University of Hong Kong, Hong Kong, SAR, People's Republic of China. 5. Ningbo Key Laboratory of Behavioral Neuroscience, Zhejiang Provincial Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, Ningbo, People's Republic of China. cuiwei@nbu.edu.cn. 6. Department of Physiology, School of Medicine, Ningbo University. Ningbo, Ningbo, 315211, People's Republic of China. cuiwei@nbu.edu.cn. 7. School of Chinese Medicine, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, SAR, People's Republic of China. lisaxian@cuhk.edu.hk. 8. Brain Research Centre, School of Chinese Medicine, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, SAR, People's Republic of China. lisaxian@cuhk.edu.hk.
Abstract
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 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. CONCLUSION: 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.
INTRODUCTION:Gelsemine is a natural alkaloid extracted from Gelsemium elegansBenth., 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 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. CONCLUSION: 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.
Authors: Fatemeh Zahedipour; Seyede Atefe Hosseini; Neil C Henney; George E Barreto; Amirhossein Sahebkar Journal: Neural Regen Res Date: 2022-08 Impact factor: 5.135