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鞣花酸改善早发性阿尔茨海默病症状:行为学与生理学关联

Ellagic acid improves the symptoms of early-onset Alzheimer's disease: Behavioral and physiological correlates.

作者信息

Jha Abhishek B, Chaube Udit J, Jha Ashish B

机构信息

Department of Pharmacology, Institute of Pharmacy, Nirma University, Ahmedabad, 382481, Gujarat, India.

Department of Pharmaceutical Chemistry, Institute of Pharmacy, Nirma University, Ahmedabad, 382481, Gujarat, India.

出版信息

Heliyon. 2024 Sep 7;10(18):e37372. doi: 10.1016/j.heliyon.2024.e37372. eCollection 2024 Sep 30.

Abstract

is a globally recognized staple food, rich in essential phyto-phenolic compounds such as γ-Oryzanol (OZ), Ferulic acid (FA), and Ellagic acid (EA). These phytochemicals are known for their potential to beneficially modulate molecular biochemistry. The present investigation aimed to evaluate the neuroprotective and cognitive enhancement effects of phyto-phenolics in a model of early-onset Alzheimer's disease (EOAD) induced by Aβ (1-42) in animals. studies suggested that FA, OZ, and EA have target specificity for Aβ, with EA being further selected based on its potent Aβ anti-aggregatory effects for exploring neurodegenerative conditions. The experiments demonstrated that EA exerts therapeutic effects in Aβ-induced EOAD, modulating both biochemical and behavioral outcomes. EA treatment at two dose levels, EA and EA (70 μM and 140 μM, respectively, administered i.c.v.), significantly counteracted Aβ aggregation and modulated the Ca⁺/Calpain/GSK-3β/CDK5 signaling pathways, exhibiting anti-tauopathy effects. Additionally, EA was shown to exert anti-inflammatory effects by preventing astroglial activation, modulating FAIM-L expression, and protecting against TNF-α-induced apoptotic signals. Moreover, the neuromodulatory effects of EA were attributed to the regulation of CREB levels, Dnm-1 expression, and synaptophysin levels, thereby enhancing LTP and synaptic plasticity. EA also induced beneficial cytological and behavioral changes, improving both long-term and short-term spatial memory as well as associative learning behavior in the animal model, which underscores its cognitive enhancement properties.

摘要

是一种全球公认的主食,富含γ-谷维素(OZ)、阿魏酸(FA)和鞣花酸(EA)等必需植物酚类化合物。这些植物化学物质以其有益调节分子生物化学的潜力而闻名。本研究旨在评估植物酚类物质在动物Aβ(1-42)诱导的早发性阿尔茨海默病(EOAD)模型中的神经保护和认知增强作用。研究表明,FA、OZ和EA对Aβ具有靶点特异性,基于其强大的Aβ抗聚集作用,进一步选择EA来探索神经退行性疾病。实验表明,EA在Aβ诱导的EOAD中发挥治疗作用,调节生化和行为结果。在两个剂量水平(分别为70μM和140μM,脑室内给药)给予EA治疗,显著对抗Aβ聚集并调节Ca⁺/钙蛋白酶/GSK-3β/CDK5信号通路,表现出抗tau病变作用。此外,EA通过防止星形胶质细胞活化、调节FAIM-L表达和抵抗TNF-α诱导的凋亡信号发挥抗炎作用。此外,EA的神经调节作用归因于对CREB水平、Dnm-1表达和突触素水平的调节,从而增强长时程增强(LTP)和突触可塑性。EA还诱导有益的细胞学和行为变化,改善动物模型中的长期和短期空间记忆以及联想学习行为,这突出了其认知增强特性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/87ad/11416286/97b805579e77/ga1.jpg

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