Serum and Brain Metabolomic Variations Reveal Perturbation of Sleep Deprivation on Rats and Ameliorate Effect of Total Ginsenoside Treatment

Abstract

Sleep loss or sleep deprivation (SD) refers to shorter sleep than average baseline need, and SD has been a serious problem of modern societies which affects health and well-being. Panax ginseng is a well-known traditional Chinese medicine (TCM). Our previous study has demonstrated that total ginsenosides (GS), the extracts from Panax ginseng, could effectively improve cognition and behavior on SD rats. However, little is known about its metabolomic study. In this study, serum and brain metabolomic method based on gas chromatography coupled with mass spectrometry (GC/MS) was employed to evaluate the efficacy and study the mechanism of GS on a rat model of SD. With pattern recognition analysis of serum and brain tissue metabolite profile, a clear separation of the model group and control group was acquired for serum and brain tissue samples; the MGS (model + GS) group showed a tendency of recovering when compared to control group, which was consistent with behavioral and biochemical parameters. 39 and 40 potential biomarkers of brain tissues and serum samples, respectively, were identified and employed to explore the possible mechanism. Our work revealed that GS has significant protective effects on SD, and metabolomics is a useful tool for evaluating efficacy and elucidating mechanism in TCM.

Metabolomics in Sleep, Insomnia and Sleep Apnea

“…The three BCAAs are key elements in the de novo synthesis of glutamate [ 93 ]. An excess of BCAAs caused by sleep-wake disorders, can reduce the uptake of the serotonin precursor tryptophan and the catecholamine precursors tyrosine and phenylalanine; therefore, the decreased inhibitory neurotransmitters (serotonin and catecholamines) and increased excitatory neurotransmitters (glutamate and aspartate) might maintain the waking of the brain [ 68 ]. Elevation of BCAAs during nighttime has also been linked to daytime fatigue, likely due to their capacity to reduce the transport of tryptophan through the blood–brain barrier, finally affecting serotonin levels [ 94 ].…”

Comparative metabolome analysis of serum changes in sheep under overgrazing or light grazing conditions

“…Lower levels of hypoxanthine can be considered a sign of less degradation of adenosine, indicating higher concentrations of adenosine in biofluids in the body [33]. In sleep loss or sleep deprivation experimental model groups, serum adenosine was elevated, but its product of degradation, hypoxanthine, was decreased, suggesting disordered nucleotide metabolism [34]. It was reported that with increasing grazing intensity, sheep decreased their time at rest to maintain their grazing time [17].…”

“…Lower levels of 4-pyridoxic acid reflect vitamin B6 dysfunction [43]. The active form of vitamin B6 is involved in various enzyme reactions that are related to amino acid and lipid metabolism [34]. In contrast, defects in vitamin B6 affected antioxidant defenses in animal livers [45,46].…”

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“…Detailed analysis of constituents of a sample by hyphenated techniques such as gas chromatography -mass spectrometry (GC/MS) is called profiling. With the help of these techniques, a comprehensive chromatographic profile of a sample with the relative or absolute quantification of all compounds of the sample could be obtained 4 . It is estimated that in plant kingdom approximately 200,000 compounds may be present and of these, about 10,000 are known 5 .…”

“…Such methods have high accuracy and precision which is further increased with the use of stable isotope labelled internal standards. But, stable isotope labelled standards are highly expensive and are commercially available only for a limited number of compounds 4 . In non-targeted analysis all compounds which show peaks above certain intensity, can be characterized on the basis of their GC retention indices and mass spectral patterns.…”