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

Abstract

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.

Dexmedetomidine Ameliorates Hippocampus Injury and Cognitive Dysfunction Induced by Hepatic Ischemia/Reperfusion by Activating SIRT3-Mediated Mitophagy and Inhibiting Activation of the NLRP3 Inflammasome in Young Rats

“…In contrast, SIRT2 has recently been shown to be an acetylation switch of the NLRP3 inflammasome to repress its activation [ 25 , 26 ]. SIRT3 is a key mitochondrial protein deacetylase, highly expressed in the brain [ 27 ], which has significant effects on oxidative stress, mitochondrial function, mitophagy, pyroptosis, and apoptosis [ 28 ]. Recent research proved that increasing SIRT3 levels alleviated mitochondrial dysfunction by normalizing mitochondrial bioenergetics in Parkinson's [ 29 ] and Alzheimer's diseases [ 30 ].…”

Piceatannol alleviate ROS‐mediated PC‐12 cells damage and mitochondrial dysfunction through SIRT3/FOXO3a signaling pathway

“…Although previous study has reported that piceatannol could attenuate neurological deficits and behavioral disorder in animal model (Zhang, Deng, et al, 2018), the neuroprotective mechanism of piceatannol has not been fully elucidated. Sirtuin 3 (SIRT3), a mitochondrial localized NAD + ‐dependent deacetylase, modulates cellular energy metabolism and stress resistance (Liu, Wang, Wang, et al, 2020). A growing number of evidences has shown that SIRT3 is involved in neuroprotective activity.…”

5‐Heptadecylresorcinol Protects against Atherosclerosis in Apolipoprotein E‐Deficient Mice by Modulating SIRT3 Signaling: The Possible Beneficial Effects of Whole Grain Consumption

“…Animal dosage of AR‐C17 (30 and 150 mg kg −1 ) was determined based on the recommended daily consumption of whole grain rye of 60–300 g 60 kg −1 body weight according to the reported study. [ 11 ]…”

“…[ 15 ] AR‐C17 also alleviated cognitive decline of APP/PS1 transgenic mice by inhibiting microglia activation and modulating gut microbiota. [ 11 ] However, there is no relevant study demonstrating the effect of AR‐C17 on atherosclerosis, and the mechanism of action is still unclear.…”

“…As a major homologue and an active ingredient of ARs, the biomarker of whole grain wheat and rye consumption, 5-heptadecylresorcinol (AR-C17) along with ARs have been proven with multiple health-promoting activities. [11][12][13] For instance, wheat ARs have been evidenced to inhibit the oxidative damage of ARPE-19 cell through modulating Nrf2/HO-1 pathway. [14] Likewise, AR-C17 treatment markedly alleviated oxidative stress induced neurocytes apoptosis and mitochon-drial dysfunction via activating SIRT3 signaling pathway.…”