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  

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 

机构地区：[1]Department of Medicinal Chemistry,School of Pharmacy,Fujian Medical University,Fuzhou,Fujian Province,China [2]Fujian Provincial Key Laboratory of Brain Aging and Neurodegenerative Diseases,School of Basic Medical Sciences,Fujian Medical University,Fuzhou,Fujian Province,China [3]Institute of Laboratory Animal Center,Fujian Medical University,Fuzhou,Fujian Province,China [4]Department of Neurosurgery,Neurosurgery Research Institute,The First Affiliated Hospital,Fujian Medical University,Fuzhou,Fujian Province,China [5]Department of Hyperbaric Oxygen,National Regional Medical Center,Binhai Campus of the First Affiliated Hospital,Fujian Medical University,Fuzhou,Fujian Province,China

出　　处：《Neural Regeneration Research》2025年第11期3330-3344,共15页中国神经再生研究（英文版）

基　　金：supported by the Research Foundation for Talented Scholars of Fujian Medical University,No.XRCZX2018014(to DZ);Startup Fund for Scientific Research,Fujian Medical University,No.2019QH1017(to CW);the Natural Science Foundation of Fujian Province,China,Nos.2021J01693(to DZ),2021J02032(to ZCY)。

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.

关 键 词：Alzheimer's disease amyloid-β ASTROCYTE cognitive impairment D30 dendritic spines GALECTIN-3 MICROGLIA NEUROINFLAMMATION neuron 

分 类 号：R749.16[医药卫生—神经病学与精神病学]