Jin Ge, Wang Li-Hua, Ji Xue-Fei, Chi Tian-Yan, Qi Yue, Jiao Qing, Xu Qian, Zhou Xiao-Yu, Zhang Rui, Zou Li-Bo
Department of Pharmacology, Life Science and Biopharmaceutics School, Shenyang Pharmaceutical University, Shenyang 110016, PR China; Department of Pharmacology, Shenyang Medical Colleges, Shenyang 110034, PR China.
Shenyang Institute of Applied Ecology, Chinese Academy of Sciences, Shenyang 110016, PR China.
Neurosci Lett. 2014 Jun 24;573:58-63. doi: 10.1016/j.neulet.2014.04.032. Epub 2014 May 5.
Xanthoceraside, a triterpenoid saponin, has been shown to reverse cognitive deficits in several Alzheimer's disease (AD) animal models. However, the effects of xanthoceraside on the Aβ deposition pathology and the APP processing in AD are unclear. Here, we show that xanthoceraside at doses of 0.08 and 0.32 mg/kg/d for 6 months significantly improved learning and memory impairment in APP transgenic mice assessed by the Y maze and novel object recognition tests. Immunohistochemical analyses revealed that xanthoceraside strongly attenuated β-amyloid deposition in the brains of APP transgenic mice. Western blotting revealed that xanthoceraside decreased tau phosphorylation protein levels at Ser396 and Ser404 in the hippocampus; xanthoceraside also decreased APP protein levels and GSK-3β phosphorylation. These results suggest that xanthoceraside could be a promising novel candidate for the therapy of AD.
文冠果苷是一种三萜皂苷，已被证明可逆转多种阿尔茨海默病（AD）动物模型中的认知缺陷。然而，文冠果苷对AD中Aβ沉积病理和APP加工的影响尚不清楚。在此，我们表明，以0.08和0.32mg/kg/d的剂量给予文冠果苷6个月，通过Y迷宫和新物体识别测试评估，可显著改善APP转基因小鼠的学习和记忆障碍。免疫组织化学分析显示，文冠果苷可强烈减弱APP转基因小鼠大脑中的β-淀粉样蛋白沉积。蛋白质免疫印迹分析显示，文冠果苷可降低海马体中Ser396和Ser404位点的tau磷酸化蛋白水平；文冠果苷还可降低APP蛋白水平和GSK-3β磷酸化水平。这些结果表明，文冠果苷可能是一种有前途的AD治疗新候选药物。
