Xue Wei, Hu Jin-feng, Yuan Yu-he, Sun Jian-dong, Li Bo-yu, Zhang Dong-ming, Li Chuang-jun, Chen Nai-hong
Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
Acta Pharmacol Sin. 2009 Sep;30(9):1211-9. doi: 10.1038/aps.2009.112. Epub 2009 Aug 17.
The aim of this study was to investigate the cognition-enhancing activity and underlying mechanisms of a triterpenoid saponin (polygalasaponin XXXII, PGS32) isolated from the roots of Polygala tenuifolia Willd.
The Morris water maze was used to evaluate the spatial learning and memory of mice. To detect the basic properties of synaptic transmission and long-term potentiation (LTP) in the dentate gyrus of rats, electrophysiological recordings were made of evoked potentials. Western blotting analysis and immunofluorescence assays were used to determine the phosphorylation of extracellular signal-regulated kinase (ERK), cAMP response element-binding protein (CREB), synapsin I and the expression of brain derived neurotrophic factor (BDNF).
When administered at 0.125, 0.5, or 2 mg/kg, PGS32 could significantly prevent scopolamine-induced cognitive impairments in mice. Intracerebroventricular (icv) administration of PGS32 greatly enhanced basic synaptic transmission in the dentate gyrus of rats and induced LTP. In primary hippocampal neurons, as well as in the hippocampus of maze-trained mice, PGS32 activated the mitogen-activated protein (MAP) kinase cascade by promoting phosphorylation of ERK, CREB and synapsin I. The expression of BDNF was also greatly enhanced in the hippocampus.
Our findings suggest that PGS32 can improve hippocampus-dependent learning and memory, possibly through improvement of synaptic transmission, activation of the MAP kinase cascade and enhancement of the level of BDNF. Therefore, PGS32 shows promise as a potential cognition-enhancing therapeutic drug.
本研究旨在探讨从远志（Polygala tenuifolia Willd.）根部分离出的三萜皂苷（远志皂苷XXXII，PGS32）的认知增强活性及其潜在机制。
采用莫里斯水迷宫评估小鼠的空间学习和记忆能力。为检测大鼠齿状回突触传递和长时程增强（LTP）的基本特性，记录诱发电位的电生理情况。采用蛋白质免疫印迹分析和免疫荧光测定法来确定细胞外信号调节激酶（ERK）、环磷腺苷效应元件结合蛋白（CREB）、突触素I的磷酸化情况以及脑源性神经营养因子（BDNF）的表达。
当以0.125、0.5或2mg/kg的剂量给药时，PGS32可显著预防东莨菪碱诱导的小鼠认知障碍。脑室内（icv）注射PGS32可极大增强大鼠齿状回的基本突触传递并诱导LTP。在原代海马神经元以及经迷宫训练的小鼠海马体中，PGS32通过促进ERK、CREB和突触素I的磷酸化激活丝裂原活化蛋白（MAP）激酶级联反应。海马体中BDNF的表达也显著增强。
我们的研究结果表明，PGS32可能通过改善突触传递、激活MAP激酶级联反应以及提高BDNF水平来改善海马体依赖的学习和记忆。因此，PGS32有望成为一种潜在的认知增强治疗药物。
