LC/MS-based metabolomics strategy to assess the amelioration effects of ginseng total saponins on memory deficiency induced by simulated microgravity

• Published in: Journal of pharmaceutical and biomedical analysis 2016-06, Vol.125, p.329-338
• Main Authors: Feng, Li, Yue, Xiao-fei, Chen, Yi-xi, Liu, Xin-min, Wang, Li-sha, Cao, Fang-rui, Wang, Qiong, Liao, Yong-hong, Pan, Rui-le, Chang, Qi
• Format: Article
• Language: English
• Subjects: Animals; Chromatography, Liquid - methods; Ginseng total saponins; Hippocampus; LC/MS; Male; Mass Spectrometry - methods; Memory Disorders - drug therapy; Memory Disorders - etiology; Memory-improving effects; Metabolomics; Panax - metabolism; Panax ginseng; Plasma; Rats; Rats, Sprague-Dawley; Saponins - therapeutic use; Weightlessness - adverse effects
• ISSN: 0731-7085; 1873-264X
• DOI: 10.1016/j.jpba.2016.04.002

[Display omitted] •Ginseng total saponins (GTS) produce significant memory-improving effects.•The memory-improving effect of GTS was studied by a LC/MS based metabolomics method.•Metabolic changes of amino acids, neurotransmitters, and sphingolipids were noted.•The study provide new insights into ginseng's memory-improving effects. 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 not only can deepen our understanding of the underlying molecular mechanisms of