Tchantchou Flaubert, Xu Yanan, Wu Yanjue, Christen Yves, Luo Yuan
Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland, Baltimore, MD 21201, USA.
FASEB J. 2007 Aug;21(10):2400-8. doi: 10.1096/fj.06-7649com. Epub 2007 Mar 13.
Standardized Ginkgo biloba extract EGb 761 exhibits beneficial effects to patients with Alzheimer's disease (AD). It was previously demonstrated that EGb 761 inhibits amyloid beta (Abeta) oligomerization in vitro, protects neuronal cells against Abeta toxicity, and improves cognitive defects in a mouse model of AD (Tg 2576). In this study, the neurogenic potential of EGb 761 and its effect on cAMP response element binding protein (CREB) were examined in a double transgenic mouse model (TgAPP/PS1). EGb 761 significantly increases cell proliferation in the hippocampus of both young (6 months) and old (22 months) TgAPP/PS1 mice, and the total number of neuronal precursor cells in vitro in a dose-dependent manner. Furthermore, Abeta oligomers inhibit phosphorylation of CREB and cell proliferation in the hippocampus of TgAPP/PS1 mice. Administration of EGb 761 reduces Abeta oligomers and restores CREB phosphorylation in the hippocampus of these mice. The present findings suggest that 1) enhanced neurogenesis by EGb 761 may be mediated by activation of CREB, 2) stimulation of neurogenesis by EGb 761 may contribute to its beneficial effects in AD patients and improved cognitive functions in the mouse model of AD, and 3) EGb 761 has therapeutic potential for the prevention and improved treatment of AD.
标准化银杏叶提取物EGb 761对阿尔茨海默病（AD）患者具有有益作用。先前已证明EGb 761在体外可抑制淀粉样β蛋白（Aβ）寡聚化，保护神经元细胞免受Aβ毒性影响，并改善AD小鼠模型（Tg 2576）中的认知缺陷。在本研究中，在双转基因小鼠模型（TgAPP/PS1）中检测了EGb 761的神经发生潜力及其对环磷酸腺苷反应元件结合蛋白（CREB）的影响。EGb 761显著增加了年轻（6个月）和老年（22个月）TgAPP/PS1小鼠海马体中的细胞增殖，并以剂量依赖方式增加了体外神经元前体细胞的总数。此外，Aβ寡聚体抑制TgAPP/PS1小鼠海马体中CREB的磷酸化和细胞增殖。给予EGb 761可减少这些小鼠海马体中的Aβ寡聚体并恢复CREB磷酸化。目前的研究结果表明：1）EGb 761增强神经发生可能是通过激活CREB介导的；2）EGb 761刺激神经发生可能有助于其对AD患者的有益作用以及改善AD小鼠模型中的认知功能；3）EGb 761对AD的预防和改善治疗具有治疗潜力。
