5-Heptadecylresorcinol, a Biomarker for Whole Grain Rye Consumption, Ameliorates Cognitive Impairments and Neuroinflammation in APP/PS1 Transgenic Mice.

Abstract

5-heptadecylresorcinol (AR-C17) is a biomarker for whole grain rye consumption, which is also an important active component with potential health benefits. The aim of this study is to investigate the protective effect of AR-C17 on cognitive deficits in amyloid precursor protein (APP)/PS1 transgenic mice. Cognitive function is evaluated using Morris water maze test. The result shows that oral administration of AR-C17 (150mg kg-1 day-1 ) for 5 months can ameliorate APP/PS1 transgenic mice memory impairment and improve learning ability. Moreover, AR-C17 treatment can notably reduce β-amyloid plaques accumulation and tau hyperphosphorylation while enhancing a disintegrin and metalloprotease 10 (ADAM10), postsynaptic density protein-95 (PSD-95), and synaptophysin protein expression in APP/PS1 transgenic mice. Furthermore, AR-C17 treatment reduces neuroinflammation by inhibiting microglial activation and astrogliosis as well as decreasing NOD-like receptor family, pyrin domain-containing 3 (NLRP3) inflammasome-mediated IL-1β production and activating the sirtuin 3 (SIRT3)/superoxide dismutase 2 (SOD2) signaling pathway. Additionally, AR-C17 consumption significantly modulated gut dysbiosis in APP/PS1 transgenic mice through improving the relative abundance of Akkermansia and Lactobacillus while reducing the abundance of Clostridium and Desulfovibr according to16S rRNA analysis. AR-C17 can be applied as a potential functional food ingredient to ameliorate cognitive impairments and prevent Alzheimer's disease.