LC/MS-based metabolomics strategy to assess the amelioration effects of ginseng total saponins on memory deficiency induced by simulated microgravity
LC/MS-based metabolomics strategy to assess the amelioration effects of ginseng total saponins on memory deficiency induced by simulated microgravity
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DOI：
10.1016/j.jpba.2016.04.002
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发表时间：
2016-06-05
影响因子：
3.4
通讯作者：
Chang, Qi
中科院分区：
文献类型：
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作者：
Feng, Li;Yue, Xiao-fei;Chang, Qi
微重力诱发的记忆缺陷严重影响航天员在航天飞行中的学习记忆能力，目前缺乏有效的应对措施。人参。在亚洲国家被用作益智草药已有数千年的历史。皂苷被认为是其主要活性成分。先前的研究表明，人参皂苷可以预防由各种因素引起的记忆缺陷。尽管如此，其益智作用的潜在机制仍然在很大程度上是未知的。在本研究中，我们采用代谢组学方法评估了人参总皂苷（GTS）对模拟微重力后肢卸车大鼠的记忆改善作用。后肢卸荷（HU） 7天后，采用液相色谱-质谱（LC-MS）非靶向代谢组学方法检测GTS干预前后大鼠血浆和海马代谢谱变化。随后，采用LC-MS/MS法测定8种海马神经递质。最后，进行基于LC-MS/MS的靶向代谢组学来验证非靶向分析中发现的生物标志物。此外，为了支持代谢组学结果，进行了被动回避（PA）试验、尼氏染色和血浆皮质酮（CORT）水平测定。结果表明，HU可导致7种神经递质发生变化，并显著改变血浆和海马代谢谱。GTS可以恢复大部分失衡的神经递质，特别是谷氨酸和乙酰胆碱，并纠正各种与学习和记忆相关的生物标志物，如天冬酰胺、苯丙氨酸、酪氨酸、色氨酸和胆碱。此外，GTS可以显著改善hu诱导的记忆缺陷，保护海马神经元免受损伤，并下调升高的CORT水平。综上所述，GTS主要通过调节氨基酸、神经递质、胆碱、犬尿氨酸和鞘脂的代谢发挥记忆改善作用。本研究结果不仅加深了我们对mg诱导记忆障碍的分子机制的理解，而且为选择人参作为对抗mg诱导记忆缺陷的对策提供了科学依据。(C) 2016 Elsevier B.V.版权所有
Microgravity-induced memory deficiency seriously affects learning and memory ability of the astronaut during spaceflight, with few effective countermeasures. Panax ginseng C. A. Mey. has been used as a nootropic herb for thousands of years in Asian countries. Saponins are recognized as its major active components. Previous studies have shown that ginseng saponins offer protection against memory deficits caused by various factors. Nevertheless, the underlying mechanisms of their nootropic effects are still largely unknown. In this study, we evaluated the memory-improving effects of ginseng total saponins (GTS) on simulated microgravity hindlimb-unloaded rats using a metabolomics approach. After being exposed to a 7-days hindlimb unloading (HU), variations of plasmatic and hippocampal metabolic profiles of rats with and without GTS intervention were examined by a liquid chromatography-mass spectrometry (LC-MS) based untargeted metabolomics method. Subsequently, 8 hippocampal neurotransmitters were determined using a LC-MS/MS method. Finally, a LC-MS/MS based targeted metabolomics was performed to validate biomarkers found in the untargeted analysis. Besides, to support the metabolomics results, passive avoidance (PA) test, Nissl staining, and plasmatic corticosterone (CORT) levels determination were performed. The results showed that HU could lead to variations of 7 neurotransmitters and significantly different plasmatic and hippocampal metabolic profiles. GTS could restore most of the imbalanced neurotransmitters, especially glutamic acid and acetylcholine, and correct the levels of various disturbed learning and memory relevant biomarkers such as asparagine, phenylalanine, tyrosine, tryptophan, and choline. In addition, GTS could markedly ameliorate HU-induced memory deficiency, protect hippocampal neurons from damage, and down-regulate elevated CORT levels. In conclusion, GTS exhibits memory-improving effects mainly through regulating the metabolism of amino acids, neurotransmitters, choline, kynurenine, and sphingolipids. The findings of this study notonly can deepen our understanding of the underlying molecular mechanisms of MG-induced memory disorders, but also provide scientific evidence for choosing ginseng as a countermeasure against MG-induced memory deficiency. (C) 2016 Elsevier B.V. All rights reserved.