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
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 pha...
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| Format: | Article |
| Language: | English |
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Wolters Kluwer Medknow Publications
2025-11-01
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| Series: | Neural Regeneration Research |
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| Online Access: | https://journals.lww.com/10.4103/NRR.NRR-D-23-01890 |
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| author | Xueyan Liu Wei Wu Xuejuan Li Chengyan Wang Ke Chai Fanru Yuan Huijuan Zheng Yuxing Yao Chenlu Li Zu-Cheng Ye Daijun Zha |
| author_facet | Xueyan Liu Wei Wu Xuejuan Li Chengyan Wang Ke Chai Fanru Yuan Huijuan Zheng Yuxing Yao Chenlu Li Zu-Cheng Ye Daijun Zha |
| author_sort | Xueyan Liu |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-8c9f9f992c344600bd2633423d4a52af |
| institution | Kabale University |
| issn | 1673-5374 1876-7958 |
| language | English |
| publishDate | 2025-11-01 |
| publisher | Wolters Kluwer Medknow Publications |
| record_format | Article |
| series | Neural Regeneration Research |
| spelling | doaj-art-8c9f9f992c344600bd2633423d4a52af2025-01-07T09:49:29ZengWolters Kluwer Medknow PublicationsNeural Regeneration Research1673-53741876-79582025-11-0120113330334410.4103/NRR.NRR-D-23-01890The compound (E)-2-(3,4-dihydroxystyryl)-3-hydroxy-4H-pyran-4-one alleviates neuroinflammation and cognitive impairment in a mouse model of Alzheimer’s diseaseXueyan LiuWei WuXuejuan LiChengyan WangKe ChaiFanru YuanHuijuan ZhengYuxing YaoChenlu LiZu-Cheng YeDaijun ZhaPrevious 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.https://journals.lww.com/10.4103/NRR.NRR-D-23-01890alzheimer’s diseaseamyloid-βastrocytecognitive impairmentd30dendritic spinesgalectin-3microglianeuroinflammationneuron |
| spellingShingle | Xueyan Liu Wei Wu Xuejuan Li Chengyan Wang Ke Chai Fanru Yuan Huijuan Zheng Yuxing Yao Chenlu Li Zu-Cheng Ye Daijun Zha 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 Neural Regeneration Research alzheimer’s disease amyloid-β astrocyte cognitive impairment d30 dendritic spines galectin-3 microglia neuroinflammation neuron |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| topic | alzheimer’s disease amyloid-β astrocyte cognitive impairment d30 dendritic spines galectin-3 microglia neuroinflammation neuron |
| url | https://journals.lww.com/10.4103/NRR.NRR-D-23-01890 |
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