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

Kengo Iwata; Qingqing Wu; Farhana Ferdousi; Kazunori Sasaki; Kenichi Tominaga; Haruhisa Uchida; Yoshinobu Arai; Francis G Szele; Hiroko Isoda

doi:10.3389/fcell.2020.573487

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

Front Cell Dev Biol. 2020 Oct 6:8:573487. doi: 10.3389/fcell.2020.573487. eCollection 2020.

Authors

Kengo Iwata^{1

2}, Qingqing Wu^{3

4}, Farhana Ferdousi^{3

5}, Kazunori Sasaki^{3

5}, Kenichi Tominaga⁵, Haruhisa Uchida², Yoshinobu Arai², Francis G Szele⁴, Hiroko Isoda^{1

3

5

6}

Affiliations

¹ School of Integrative and Global Majors, University of Tsukuba, Tsukuba, Japan.
² Nippo Co., Ltd., Daito, Japan.
³ Alliance for Research on the Mediterranean and North Africa, University of Tsukuba, Tsukuba, Japan.
⁴ Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, United Kingdom.
⁵ AIST-University of Tsukuba Open Innovation Laboratory for Food and Medicinal Resource Engineering (FoodMed-OIL), AIST, University of Tsukuba, Tsukuba, Japan.
⁶ Faculty of Life and Environmental Sciences, University of Tsukuba, Tsukuba, Japan.

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.

Keywords: SAMP8; cognitive function; energy metabolism; neural development; polyphenol; sugarcane top.