Quercetin‐3‐O‐Glucuronide Alleviates Cognitive Deficit and Toxicity in Aβ1‐42‐Induced AD‐Like Mice and SH‐SY5Y Cells

Nov 3, 2020Molecular nutrition & food research

Quercetin-3-O-Glucuronide reduces memory problems and cell damage in mice and cells with Alzheimer's-like brain changes

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Abstract

Quercetin-3-O-glucuronide (Q3G) may alleviate cognitive dysfunction in Alzheimer's disease by addressing brain insulin resistance and gut microbiome imbalance.

Q3G reduces neuroinflammation and brain insulin resistance in a mouse model of Alzheimer's disease.
It decreases apoptosis in Aβ-treated human neural cells.
Q3G lowers amyloid-β accumulation and Tau hyperphosphorylation in the brain.
The treatment restores levels of CREB and BDNF in the hippocampus.
Q3G improves gut microbiota balance and increases short-chain fatty acids that are reduced by amyloid-β.

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SCOPE: Alzheimer's disease (AD) is characterized by amyloid-β (Aβ) related imbalance, Tau-hyperphosphorylation, and neuroinflammation, in which Aβ and neuroinflammation can induce brain insulin resistance (IR). Gut microbiome disorder is correlated with inflammation in AD. As of yet, there are no effective treatments clinically. Thus, it is focused on the potential benefit of quercetin-3-O-glucuronide (Q3G), a pharmacologically active flavonol glucuronide, on AD treatment by regulating brain IR and the gut microbiome.

METHODS AND RESULTS: AD mice model built through intracerebroventricular injection of Aβand AD cell model developed through the SH-SY5Y cell line and Aβare used to explore the protective effects of Q3G on AD. Neurobehavioral test, brain insulin signaling pathway, and high-throughput pyrosequencing of 16S rRNA are assessed. Data show that Q3G attenuates neuroinflammation and brain IR in Aβ-injected mice and relieves apoptosis in Aβ-treated SH-SY5Y cells by interrupting the downstream insulin signaling. Q3G ameliorates Aβ accumulation and Tau phosphorylation, restores CREB and BDNF levels in the hippocampus , and reverses Aβ-induced cognitive impairment. Besides, Q3G restores Aβ-induced reduction of short-chain fatty acids (SCFAs) and gut microbiota dysbiosis. 1-42 1-42 1-42 1-42 1-42 1-42

CONCLUSION: Q3G can alleviate brain IR through directly acting on the brain or modulating the gut-brain axis, ultimately to relieve Aβ-induced cognitive dysfunction. 1-42

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Quercetin‐3‐O‐Glucuronide Alleviates Cognitive Deficit and Toxicity in Aβ1‐42‐Induced AD‐Like Mice and SH‐SY5Y Cells

Abstract

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