Journal
MOLECULAR NUTRITION & FOOD RESEARCH
Volume 65, Issue 6, Pages -Publisher
WILEY
DOI: 10.1002/mnfr.202000660
Keywords
Alzheimer' s disease; brain insulin resistance; gut microbiota; inflammation; quercetin‐ 3‐ O‐ glucuronide
Categories
Funding
- National Natural Science Foundation of China [NSFC81472978]
- Fundamental Research Funds for the Central Universities [2019kfyXMBZ050]
- Angel Nutrition Research Fund [AF2019001]
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This study demonstrated that quercetin-3-O-glucuronide (Q3G) can protect AD mouse and cell models by improving neuroinflammation, brain insulin resistance, and gut microbiome dysbiosis. Q3G not only ameliorates various pathological changes associated with AD, but also helps restore Aβ-induced cognitive impairment.
Scope Alzheimer's disease (AD) is characterized by amyloid-beta (A beta) related imbalance, Tau-hyperphosphorylation, and neuroinflammation, in which A beta 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 A beta(1-42) and AD cell model developed through the SH-SY5Y cell line and A beta(1-42) are 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 A beta(1-42)-injected mice and relieves apoptosis in A beta(1-42)-treated SH-SY5Y cells by interrupting the downstream insulin signaling. Q3G ameliorates A beta accumulation and Tau phosphorylation, restores CREB and BDNF levels in the hippocampus , and reverses A beta(1-42)-induced cognitive impairment. Besides, Q3G restores A beta(1-42)-induced reduction of short-chain fatty acids (SCFAs) and gut microbiota dysbiosis. Conclusion Q3G can alleviate brain IR through directly acting on the brain or modulating the gut-brain axis, ultimately to relieve A beta(1-42)-induced cognitive dysfunction.
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