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

Scope 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. Methods and results Cognitive function is evaluated using Morris water maze test. The result shows that oral administration of AR‐C17 (150 mg 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. Conclusion AR‐C17 can be applied as a potential functional food ingredient to ameliorate cognitive impairments and prevent Alzheimer's disease. 5‐heptadecylresorcinol (AR‐C17) is a biomarker for whole grain rye consumption, which is also an important active component with potential health benefits. In this study, AR‐C17 consumption could ameliorate cognitive impairments and neuroinflammation in amyloid precursor protein (APP)/PS1 transgenic mice through activation of the sirtuin 3/superoxide dismutase 2 signaling pathway and modulating gut microbiota.