Neural Regeneration Research ›› 2025, Vol. 20 ›› Issue (11): 3330-3344.doi: 10.4103/NRR.NRR-D-23-01890

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The compound (E)-2-(3,4-dihydroxystyryl)-3-hydroxy4H-pyran-4-one alleviates neuroinflammation and cognitive impairment in a mouse model of Alzheimer’s disease

Xueyan Liu1, 2, #, Wei Wu2, #, Xuejuan Li1, 2, Chengyan Wang3 , Ke Chai2 , Fanru Yuan1, 2, Huijuan Zheng1, 2, Yuxing Yao1 , Chenlu Li4, 5, *, Zu-Cheng Ye2, *, Daijun Zha1, *   

  1. 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
  • Online:2025-11-15 Published:2025-02-25
  • Contact: Chenlu Li, MD, lichenlu@fjmu.edu.cn; Zu-Cheng Ye, PhD, zcye@fjmu.edu.cn; Daijun Zha, PhD, zhadj@fjmu.edu.cn.
  • Supported by:
    The study was supported by the Research Foundation for Talented Scholars of Fujian Medical University, No. XRCZX2018014 (to DZ), the Natural Science Foundation of Fujian Province, China, Nos. 2021J01693 (to DZ), 2021J02032 (to ZCY), and Startup Fund for Scientific Research, Fujian Medical University, No. 2019QH1017 (to CW).

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Abstract: 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-β introduced 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.

Key words: Alzheimer’s disease, amyloid-β, astrocyte, cognitive impairment, D30, dendritic spines, galectin-3, microglia, neuroinflammation, neuron