Quercetin is protective against short‐term dietary advanced glycation end products intake induced cognitive dysfunction in aged ICR mice

Abstract

Dietary advanced glycation end products (dAGEs) might be potential toxins involved in the pathogenesis of Alzheimer’s disease (AD). Quercetin is a flavonoid possessing neuroprotective effects. We aimed to explore whether a 21 days of dAGEs intake would result in cognitive dysfunction in aged ICR mice, and the protective effects of quercetin, with potential mechanisms explored. Fourteen‐month old ICR mice were randomly assigned into four groups, that is, Control, AGEs, quercetin, and AGE diet supplemented with quercetin. Key markers involved in Aβ, tau, and neuroinflammation from hippocampus and cortex were measured via western blot. Gut microbiota and short chain fatty acids profiles from intestinal contents were measured via 16S rRNA gene sequencing and gas chromatography (GC), respectively. Quercetin alleviated cognitive impairment induced by dAGEs in aged mice. This might be associated with that quercetin reduced cathepsin B, tau phosphorylation, and neuroinflammation, and elevated α‐diversity index (ACE, Chao1, and Shannon index), and reduced phylum Verrucomicrobia of gut microbiota. Practical applications Alzheimer’s disease (AD) has been regarded as the commonest cause of progressive dementia for the elderly. This study is the very first to demonstrate that even a short‐term dietary advanced glycation end product (dAGEs) intake induced impaired cognitive function in aged ICR mice, and querectin is capable of reversing dAGEs‐induced cognitive dysfunction. Reduced tau phosphorylation, neuroinflammation, and altered gut microbiota profiles may be involved in querectin’s protective effects against dAGEs‐induced cognitive impairment. Our study suggested that quercetin supplementation might be beneficial for improving cognitive function in elderly subjects with high consumption of dAGEs such as grilling, frying, and broiling of food.

Cognitive-Behavioural Correlates of Dysbiosis: A Review

“…In contrast, the level of propionate was found to be associated with cognitive dysfunction when examining the faecal content of mice previously transplanted with gut microbiota from AD patients [ 37 ]. Similar results have been reported in mice with cognitive impairment induced by dietary advanced glycation end products [ 38 ]. The 3xTg-AD mice also showed elevated propionate levels in both faeces and brain [ 25 ].…”

“…The 3xTg-AD mice also showed elevated propionate levels in both faeces and brain [ 25 ]. Animal studies focusing on the effects of acetate and butyrate on cognitive function reported conflicting results [ 23 , 30 , 34 , 38 ]. This inconsistency could relate to the different models used to generate cognitive impairment along with the different animal strains.…”

The effect of 24-week continuous intake of quercetin-rich onion on age-related cognitive decline in healthy elderly people: a randomized, double-blind, placebo-controlled, parallel-group comparative clinical trial

“…(21) In vivo, on the other hand, plasma exosome loaded with quercetin improved the cognitive function of Alzheimer model mice, (22) and quercetin alleviated the cognitive impairment of aged ICR mice induced by advanced glycation end products. (23) We previously conducted a randomized, placebo-controlled, double-blind, parallel-group comparison study evaluating the effect of continuous intake of quercetin-rich onions 'Quel Gold' and 'Sarasara Gold' in 50 elderly subjects. (4) The study showed that continuous intake of quercetin-rich onion powder failed to improve cognitive function as evaluated by Mini-Mental State Examination (MMSE) and cognitive impairment rating scale scores, but an improvement of MMSE scores was observed in a younger group in a subclass analysis.…”

Immature Persimmon Suppresses Amyloid Beta (Aβ) Mediated Cognitive Dysfunction via Tau Pathology in ICR Mice

“…Ellagic acid contained in IPEE reduced the BAX/BCl-2 ratio and expression of caspase 3 in D-galactose-induced rats [75]. In addition, quercetin suppressed cognitive deficit dietary advanced glycation end product-induced aged mice by reducing cathepsin B, tau phosphorylation and neuroinflammation such as the glial fibrillary acidic protein (GFAP) and Ibα1 [76]. Similar to a previous study, IPEE increased the neuronal survival by regulating the expression of p-JNK, p-Akt and p-GSK3β through JNK/Akt pathway regulation.…”