Abstract
Age-related biological alterations in brain function increase the risk of mild cognitive impairment and dementia, a global problem exacerbated by aging populations in developed nations. Limited pharmacological therapies have resulted in attention turning to the promising role of medicinal plants and dietary supplements in the treatment and prevention of dementia. Sugarcane (Saccharum officinarum L.) top, largely considered as a by-product because of its low sugar content, in fact contains the most abundant amounts of antioxidant polyphenols relative to the rest of the plant. Given the numerous epidemiological studies on the effects of polyphenols on cognitive function, in this study, we analyzed polyphenolic constituents of sugarcane top and examined the effect of sugarcane top ethanolic extract (STEE) on a range of central nervous system functions in vitro and in vivo. Orally administrated STEE rescued spatial learning and memory deficit in the senescence-accelerated mouse prone 8 (SAMP8) mice, a non-transgenic strain that spontaneously develops a multisystemic aging phenotype including pathological features of Alzheimer’s disease. This could be correlated with an increased number of hippocampal newborn neurons and restoration of cortical monoamine levels in STEE-fed SAMP8 mice. Global genomic analysis by microarray in cerebral cortices showed multiple potential mechanisms for the cognitive improvement. Gene set enrichment analysis (GSEA) revealed biological processes such as neurogenesis, neuron differentiation, and neuron development were significantly enriched in STEE-fed mice brain compared to non-treated SAMP8 mice. Furthermore, STEE treatment significantly regulated genes involved in neurotrophin signaling, glucose metabolism, and neural development in mice brain. Our in vitro results suggest that STEE treatment enhances the metabolic activity of neuronal cells promoting glucose metabolism with significant upregulation of genes, namely PGK1, PGAM1, PKM, and PC. STEE also stimulated proliferation of human neural stem cells (hNSCs), regulated bHLH factor expression and induced neuronal differentiation and astrocytic process lengthening. Altogether, our findings suggest the potential of STEE as a dietary intervention, with promising implications as a novel nutraceutical for cognitive health.
Highlights
Cognitive decline, such as memory loss and learning deficit, is highly associated with aging
We determined the effects of Sugarcane Top Ethanolic Extract (STEE) on hippocampal neurogenesis and cortical monoamine levels in SAMP8 mice brains by immunohistochemical and biochemical analysis, respectively
No significant difference was found between groups, STEE showed a non-significant trend of elevated BrdU+DCX+ newborn neurons. These results indicate that the cognitive decline of SMAP8 was independent of Adult Hippocampal Neurogenesis (AHN), but that the rescue effect of STEE might be correlated with the increased AHN and further neurodevelopment
Summary
Cognitive decline, such as memory loss and learning deficit, is highly associated with aging. This has been implicated to be mediated by oxidative stress, mitochondrial dysfunction, and defective apoptotic processes in the process of normal brain aging (Ginneken, 2017). Other protein abnormalities such as increased amyloid-β (Aβ) plaques, phosphorylated tau and neurofibrillary tangles, and Lewy bodies are the pathological hallmarks of severe brain disorders, including Alzheimer’s disease (AD). Age-related brain disorders are generally accompanied by other pathologies, including cortical ( hippocampal) shrinkage, abnormal immune response and neurogenesis, and decreased neurotransmitter concentration, which could theoretically be pharmacological targets (Nelson and Tabet, 2015; Poulose et al, 2017). Pharmacological therapies are currently limited, and recently attention has turned to the role of dietary interventions or nutraceuticals in this respect (Williams et al, 2011; Howes et al, 2020)
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