Timosaponin AIII, a saponin isolated from Anemarrhena asphodeloides, ameliorates learning and memory deficits in mice
Timosaponin AIII, a saponin isolated from Anemarrhena asphodeloides, ameliorates learning and memory deficits in mice
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DOI：
10.1016/j.pbb.2009.04.021
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发表时间：
2009-08-01
影响因子：
3.6
通讯作者：
Kim, Dong-Hyun
中科院分区：
文献类型：
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作者：
Lee, Bomi;Jung, Kangsik;Kim, Dong-Hyun
知母为百合科植物知母。其主要成分为芒果苷等苍耳酮类化合物和刺五加皂苷AIII、萨尔萨皂苷元等甾体皂苷类化合物，在中药中具有解热、抗炎、抗糖尿病、抗血小板聚集、抗抑郁等作用。在本研究中，我们研究了这些皂苷在东莨菪碱处理的小鼠中的增强记忆作用。在人参皂苷中，刺五加皂苷AIII(TA3)在被动回避实验和Morris水迷宫实验中能显著逆转东莨菪碱所致的小鼠学习记忆障碍。TA3还能提高东莨菪碱处理小鼠海马乙酰胆碱水平，并呈剂量依赖性抑制乙酰胆碱酯酶(AChE)活性(IC50值，35.4mU/L)。给小鼠灌胃TA3(50 mg/kg)，用高效液相色谱和串联质谱仪测定血药浓度时，TA3的C峰出现在给药后4~6h。TA3在习得试验前5h给药的记忆增强作用比给药前1h更明显。东莨菪碱治疗可增加小鼠脑内肿瘤坏死因子-α和白介素1β的表达。而TA3和东莨菪碱可抑制肿瘤坏死因子-α和白介素1-β的表达。这些结果表明，东莨菪碱可能会导致学习和记忆障碍，炎症会使学习和记忆障碍更加复杂。TA3还可抑制肿瘤坏死因子-α或东莨菪碱诱导的BV-2小胶质细胞和SK-N-SH神经母细胞瘤细胞中核因子-kappaB信号的激活。然而，TA3可能主要通过抑制AChE来改善记忆障碍。皇冠版权所有(C)2009由爱思唯尔公司出版。保留所有权利。
Anemarrhena asphodeloides Bunge (AA, family Liliaceae). which primarily contains xantones, such as mangiferin, and steroidal saponins, such as timosaponin AIII and sarsasapogenin, has been used as an antipyretic, anti-inflammatory, anti-diabetic, anti-platelet aggregation, and anti-depressant agent in traditional Chinese medicine. in the present study, the memory-enhancing effects of these saponins were investigated in scopolamine-treated mice. Among saponins, timosaponin AIII (TA3) significantly reversed the scopolamine-induced deficits in a passive avoidance test and in the Morris water maze test. TA3 also increased hippocampal acetylcholine levels in scopolamine-treated mice and dose-dependently inhibited acetylcholinesterase (AChE) activity (IC50 value, 35.4 mu M). When TA3 (50 mg/kg) was orally administered to mice and its blood concentration was measured by liquid chromatography and tandem mass spectrometry, the C-max of TA3 occurred 4-6 h after TA3 treatment. The memory-enhancing effect of TA3 was greater when it was administered 5 h before the acquisition trial than I h before. Scopolamine treatment in mice increased brain levels of TNF-alpha and IL-1 beta expression. However, treatment with TA3 and scopolamine inhibited the increase of TNF-alpha and IL-1 beta expression. These results suggest that scopolamine may cause learning and memory deficits that are further complicated by inflammation. TA3 also inhibited the activation of NF-kappa B signaling in BV-2 microglia and in SK-N-SH neuroblastoma cells induced with TNF-alpha or scopolamine. Nevertheless, TA3 may ameliorate memory deficits, mainly by inhibiting AChE. Crown Copyright (C) 2009 Published by Elsevier Inc. All rights reserved.