The compound(E)-2-(3,4-dihydroxystyryl)-3-hydroxy-4H-pyran-4-one alleviates neuroinflammation and cognitive impairment in a mouse model of Alzheimer's disease

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外文摘要：Previous studies have shown that the compound(E)-2-(3,4-dihydroxystyryl)-3-hydroxy-4H-pyran-4-one(D30),a pyromeconic acid derivative,possesses antioxidant and anti-inflammatory properties,inhibits amyloid-β aggregation,and alleviates scopolamine-induced cognitive impairment,similar to the phase Ⅲ clinical drug resveratrol.In this study,we established a mouse model of Alzheimer's disease via intracerebroventricular injection of fibrillar amyloid-β to investigate the effect of D30 on fibrillar amyloid-β-induced neuropathology.Our results showed that D30 alleviated fibrillar amyloid-β-induced cognitive impairment,promoted fibrillar amyloid-β clearance from the hippocampus and cortex,suppressed oxidative stress,and inhibited activation of microglia and astrocytes.D30 also reversed the fibrillar amyloid-β-induced loss of dendritic spines and synaptic protein expression.Notably,we demonstrated that exogenous fibrillar amyloid-βintroduced by intracerebroventricular injection greatly increased galectin-3 expression levels in the brain,and this increase was blocked by D30.Considering the role of D30 in clearing amyloid-β,inhibiting neuroinflammation,protecting synapses,and improving cognition,this study highlights the potential of galectin-3 as a promising treatment target for patients with Alzheimer's disease.

外文关键词：

Alzheimer's diseaseamyloid-βastrocytecognitive impairmentD30dendritic spinesgalectin-3microglianeuroinflammationneuron

作者：

Xueyan Liu、Wei Wu、Xuejuan Li、Chengyan Wang、Ke Chai、Fanru Yuan、Huijuan Zheng、Yuxing Yao、Chenlu Li、Zu-Cheng Ye、Daijun Zha

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作者单位：

Department of Medicinal Chemistry,School of Pharmacy,Fujian Medical University,Fuzhou,Fujian Province,China

Fujian Provincial Key Laboratory of Brain Aging and Neurodegenerative Diseases,School of Basic Medical Sciences,Fujian Medical University,Fuzhou,Fujian Province,China

Institute of Laboratory Animal Center,Fujian Medical University,Fuzhou,Fujian Province,China

Department of Neurosurgery,Neurosurgery Research Institute,The First Affiliated Hospital,Fujian Medical University,Fuzhou,Fujian Province,China

Department of Hyperbaric Oxygen,National Regional Medical Center,Binhai Campus of the First Affiliated Hospital,Fujian Medical University,Fuzhou,Fujian Province,China

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出版年：

2025

DOI：

10.4103/NRR.NRR-D-23-01890

中国神经再生研究(英文版)

中国康复医学会

中国神经再生研究(英文版)

影响因子：0.902

ISSN：1673-5374

年,卷(期)：2025.20(11)