Sugarcane (Saccharum officinarum L.) Top Extract Ameliorates Cognitive Decline in Senescence Model SAMP8 Mice: Modulation of Neural Development and Energy Metabolism

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.

Dietary Anti-Aging Polyphenols and Potential Mechanisms

“…CQA provided at 5 mg/kg for 30 days was reported to enhance brain function of SAMP8 mice as demonstrated in the Morris water maze test [ 64 ]. Consistently, microarray analysis showed that sugarcane top ethanolic extract regulated neuron development-associated genes in the cerebral cortex of SAMP8 mice [ 63 ]. Isoorientin is a naturally occurring C -glycosyl flavone and exists in several dietary plants, including corn silks [ 65 ], rooibos tea [ 66 ], and buckwheat [ 67 ].…”

“…Supplementation of EC (10 mg/kg) per day for two weeks significantly ameliorated 6-hydroxydopamine (OHDA)-lesioned PD behavior, including increased locomotor activity and decreased rotational behavior, as compared with sham operated control group in male rats, suggesting a neuroprotective property of this compound [ 62 ]. Sugarcane ( Saccharum officinarum L.) top ethanolic extract was reported to contain several polyphenols with strong antioxidant effects, including 3-caffeoylquinic acid (CQA), 5-CQA, 3-O-feruloylquinic acid (FQA), and isoorientin [ 63 ]. CQA provided at 5 mg/kg for 30 days was reported to enhance brain function of SAMP8 mice as demonstrated in the Morris water maze test [ 64 ].…”

Interactions between Major Bioactive Polyphenols of Sugarcane Top: Effects on Human Neural Stem Cell Differentiation and Astrocytic Maturation

“…Therefore, identifying the bioactive compounds of interest in a plant extract and understanding their targeted pathways responsible for the observed health benefits need to be well understood to exploit their full potential [ 38 ]. In our previous study, we reported that STEE exerts beneficial effects on aging-related cognitive health by promoting neuronal differentiation and neuronal energy metabolism and extending the length of the astrocytic process in vitro [ 19 ]. We have identified four major polyphenols rich in STEE.…”

“…We have recently reported that oral administration of sugarcane top (ST) ethanolic extract (STEE) could ameliorate spatial learning and memory deficits in senescence-accelerated prone mouse 8 (SAMP8) that progressively develop aging phenotype. STEE improved cortical neurotransmission and stimulated hippocampal neurogenesis [ 19 ]. In vivo omics analysis and in vitro experiments with cultured cells have suggested the activation of pathways related to energy metabolism and neurodevelopment is the main mechanism underlying the above effects.…”

“…In vivo omics analysis and in vitro experiments with cultured cells have suggested the activation of pathways related to energy metabolism and neurodevelopment is the main mechanism underlying the above effects. Furthermore, a possible role of STEE in the promotion of astrocytic process formation has been suggested [ 19 ]. However, since the crude STEE consists of multicomponent mixtures, it is critical to identify the bioactive compounds of interest and elucidate their molecular modes of action to standardize the extract or scale-up of the bioactive lead compounds.…”