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

Abstract

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 Aβ1-42 and AD cell model developed through the SH-SY5Y cell line and Aβ1-42 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 Aβ1-42 -injected mice and relieves apoptosis in Aβ1-42 -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 Aβ1-42 -induced cognitive impairment. Besides, Q3G restores Aβ1-42 -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 Aβ1-42 -induced cognitive dysfunction.

• Authors: Mengdai Xu, Hao Huang, Xiaoxing Mo, Yalun Zhu, Xi Chen, Xiaoqin Li, Xiaobo Peng, Zihui Xu, Liangkai Chen, Shuang Rong, Wei Yang, Shuang Liu, Liegang Liu
• Journal: Molecular nutrition & food research (Mol Nutr Food Res) Vol. 65 Issue 6 Pg. e2000660 (03 2021) ISSN: 1613-4133 [Electronic] Germany
• PMID: 33141510 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2021 Wiley-VCH GmbH.

Chemical References

• Amyloid beta-Peptides
• Mapt protein, mouse
• Neuroprotective Agents
• Peptide Fragments
• amyloid beta-protein (1-42)
• quercetin 3-O-glucuronide
• tau Proteins
• Quercetin

Topics

• Alzheimer Disease (chemically induced, drug therapy, psychology)
• Amyloid beta-Peptides (toxicity)
• Animals
• Cell Line, Tumor
• Cognitive Dysfunction (drug therapy)
• Disease Models, Animal
• Gastrointestinal Microbiome (drug effects, genetics)
• Hippocampus (drug effects, metabolism, pathology)
• Humans
• Insulin Resistance
• Male
• Memory Disorders (chemically induced, drug therapy)
• Mice, Inbred C57BL
• Neuroblastoma (drug therapy, pathology)
• Neurons (drug effects, pathology)
• Neuroprotective Agents (pharmacology)
• Peptide Fragments (toxicity)
• Quercetin (analogs & derivatives, pharmacology)
• tau Proteins (metabolism)
• Mice