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Quercetin‐3‐ O ‐Glucuronide Alleviates Cognitive Deficit and Toxicity in Aβ 1‐42 ‐Induced AD‐Like Mice and SH‐SY5Y Cells
Author(s) -
Xu Mengdai,
Huang Hao,
Mo Xiaoxing,
Zhu Yalun,
Chen Xi,
Li Xiaoqin,
Peng Xiaobo,
Xu Zihui,
Chen Liangkai,
Rong Shuang,
Yang Wei,
Liu Shuang,
Liu Liegang
Publication year - 2021
Publication title -
molecular nutrition and food research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.495
H-Index - 131
eISSN - 1613-4133
pISSN - 1613-4125
DOI - 10.1002/mnfr.202000660
Subject(s) - neuroinflammation , neurogenesis , insulin resistance , inflammation , medicine , endocrinology , amyloid beta , pharmacology , chemistry , insulin , biology , neuroscience , disease
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 Aβ 1‐42 and AD cell model developed through the SH‐SY5Y cell line and Aβ 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 Aβ 1‐42 ‐injected mice and relieves apoptosis in Aβ 1‐42 ‐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 Aβ 1‐42 ‐induced cognitive impairment. Besides, Q3G restores Aβ 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 Aβ 1‐42 ‐induced cognitive dysfunction.