Abstract
Alzheimer’s disease (AD) is a serious neurodegenerative disease in aging populations with no effective method for the diagnosis or for the treatment. Although some physiological and pathological functional parameters have been studied, little knowledge about the changes of small metabolites in biofluids has been reported, which may result in poor diagnosis and treatment for AD. Ginsenoside Rg1 and Rb1, the pharmacologically active ingredients of ginseng, were known to have anti-AD effects, while, their mechanism remain unclear completely. This study was designed to explore globally metabolomic character of AD induced by Aβ1-42 in brain and the holistic efficacy of ginsenoside Rg1 (GRg1) and ginsenoside Rb1 (GRb1) on AD. Morris water maze was performed to examine the behavioral changes in mice. Global metabolic profiling with UPLC/MS (ultra-high-performance liquid chromatography-mass spectrometry) and principal component analysis (PCA) were performed to discover differentiating metabolites. A total of 9 potential biomarkers were identified that were associated with the metabolism of lecithin, purine, and sphingolipids in AD mice. The peak intensities of lysophosphatidylcholine, dihydrosphingosine, hexadecasphinganine, phytosphingosine were lower, while that of hypoxanthine and ceremide were higher, in AD than in control mice. GRg1 and GRb1 treatment affected lecithin and sphingolipid pathways, while not purine metabolism. These results provide the first evidence of a link between metabolite imbalance and AD, and reveal a molecular basis for the therapeutic benefits of ginsenosides in AD treatment.
Highlights
Alzheimer’s disease (AD) is among the most debilitating neurodegenerative diseases in aging populations, and is characterized by progressive memory loss and the impairment of behavioral, language, and visuospatial skills [1]
High doses of ginsenoside Rg1 (GRg1) or ginsenoside Rb1 (GRb1) reduced escape latency compared to the AD group on days 4 (P
The number of platform crossings was significantly decreased in the AD than in the control group (P
Summary
Alzheimer’s disease (AD) is among the most debilitating neurodegenerative diseases in aging populations, and is characterized by progressive memory loss and the impairment of behavioral, language, and visuospatial skills [1]. There is a critical need to identify agents that can prevent AD progression. Ginsenosides Rg1 (GRg1) and Rb1 (GRb1) as the main pharmacologically active ingredients of ginseng have been proved in their effectiveness in AD prevention and treatment [5,6]. Previous studies have mainly focused on the biochemical and pathological changes that occur in AD, while few studies have examined changes in metabolite profiles upon treatment with GRg1 and GRb1, or examined how these agents affect metabolism
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