Tenuifolin, a secondary saponin from hydrolysates of polygalasaponins, counteracts the neurotoxicity induced by Aβ25-35 Peptides in vitro and in vivo

Tenuifolin, a secondary saponin from hydrolysates of polygalasaponins, counteracts the neurotoxicity induced by Aβ25-35 Peptides in vitro and in vivo
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DOI:
10.1016/j.pbb.2014.11.010
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发表时间:
2015-01-01
影响因子:
3.6
通讯作者:
Liu, Xin-min
Liu, Xin-min
中科院分区:
心理学4区
文献类型:
--
作者:
Liu, Ya-min;Li, Zong-yang;Liu, Xin-min

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阿尔茨海默病(AD)与海马神经元损伤和认知功能下降有关。淀粉样肽的积累被认为是AD发病的关键事件。采用A - β(25-35)肽诱导的神经毒性体外筛选细胞保护因子,采用海马注射A - β(25-35)诱导的认知缺陷评价其对学习记忆的影响。我们之前的研究表明,水解的聚半乳糖皂苷(HPS)可以明显改善小鼠注射A β(25-35)引起的认知缺陷,但HPS的潜在活性成分尚不清楚。本研究的目的是分离纯化HPS的次生皂苷,筛选其体外神经保护作用,并评价其在体内的认知作用。采用多种色谱方法对HPS进行分离纯化。在A β(25-35)损伤诱导的PC12细胞中检测其神经保护作用。采用Morris水迷宫法和步进式被动回避法评价替诺依林对A β(25-35)注射所致认知障碍的保护作用。从HPS中分离得到Tenuifolin和fallax皂苷A。Tenuifolin对A β(25-35)诱导的PC12细胞凋亡具有神经保护作用,并显著改善海马内注射A β(25-35)诱导的小鼠认知缺陷。因此,tenuifolin是HPS抗A β(25-35)肽诱导的神经毒性的有效成分之一。(C) 2014爱思唯尔公司版权所有。
Alzheimer's disease (AD) is associated with damage to hippocampal neurons and declines in cognitive functions. The accumulation of amyloid peptides is regarded as a crucial event in the initiation of AD. The neurotoxicity induced by A beta(25-35) peptides was used to screen for cytoprotective factors in vitro, and the cognitive deficits induced by the injection of A beta(25-35) into the hippocampus were used to evaluate effect on learning and memory. Our previous study revealed that hydrolysate of polygalasaponins (HPS) clearly improve the cognitive deficits induced by the injection of A beta(25-35) in mice, but the potential active constituent of HPS remains unclear. The purposes of this study were to separate and purify the secondary saponins of HPS, screen for neuroprotective effects of the constituents in vitro, and to evaluate the effect of cognition in vivo. Various chromatographic methods were used to separate and purify the HPS. The neuroprotective effects were examined in A beta(25-35)-damage-induced PC12 cells. The protective effect of tenuifolin on the cognitive impairments induced by A beta(25-35) injection was assessed using the Morris water maze and step-through passive avoidance tests. Tenuifolin and fallaxsaponin A were isolated from the HPS. Tenuifolin possessed neuroprotective effects against A beta(25-35)-induced apoptosis in PC12 cells and significantly improved the cognitive deficits induced by the intrahippocampal injection of A beta(25-35) in mice. Thus, tenuifolin is one of the active constituents of HPS against the neurotoxicity induced by A beta(25-35) peptides in vitro and in vivo. (C) 2014 Elsevier Inc. All rights reserved.