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负载白藜芦醇的普朗尼克胶束通过靶向乙酰胆碱酯酶活性和程序性细胞死亡改善东莨菪碱诱导的认知功能障碍。

Resveratrol-Loaded Pluronic Micelles Ameliorate Scopolamine-Induced Cognitive Dysfunction Targeting Acetylcholinesterase Activity and Programmed Cell Death.

作者信息

Lazarova Maria, Stefanova Miroslava, Tsvetanova Elina, Georgieva Almira, Tasheva Krasimira, Radeva Lyubomira, Yoncheva Krassimira

机构信息

Institute of Neurobiology, Bulgarian Academy of Science, 1113 Sofia, Bulgaria.

Institute of Plant Physiology and Genetics, Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria.

出版信息

Int J Mol Sci. 2024 Nov 28;25(23):12777. doi: 10.3390/ijms252312777.

Abstract

Numerous experimental studies suggest the potential for resveratrol (RVT) to be useful in the Alzheimer's disease treatment, but its low bioavailability limits its application. This study aimed to assess the potential of resveratrol-loaded micelles as a neuronal delivery platform to protect rats from scopolamine-induced memory impairment. Resveratrol was incorporated into Pluronic micelles, and the effects of micellar (mRVT) and pure resveratrol (RVT) were compared in the model of scopolamine-induced dementia in male Wistar rats. Memory performance was assessed by a T maze test. The effect of the treatment on specific neurotransmitter levels and protein expression in the cortex and the hippocampus were evaluated biochemically. Our results revealed that the polymeric micelles were in nanoscale (approximately 33 nm) and reached 79% encapsulation efficiency. The treatment with mRVT demonstrated better spatial memory protective effect. The biochemical assays showed that mRVT in a dose of 10 mg/kg enhanced the effects of the pure drug in regard to noradrenalin neurotransmission and acetylcholinesterase inhibitory activity in the hippocampus. Furthermore, micellar resveratrol increased the cAMP-response element-binding protein expression in the cortex and hippocampus of rats as well as the Bcl2/BAX ratio, which indicated an anti-apoptotic effect in the experimental dementia model. In conclusion, our results indicated the potential of a micellar system loaded with resveratrol for neurodegenerative diseases treatment.

摘要

大量实验研究表明白藜芦醇(RVT)在阿尔茨海默病治疗中具有潜在作用,但其低生物利用度限制了其应用。本研究旨在评估载有白藜芦醇的胶束作为神经元递送平台保护大鼠免受东莨菪碱诱导的记忆损伤的潜力。将白藜芦醇包裹于普朗尼克胶束中,在雄性Wistar大鼠东莨菪碱诱导的痴呆模型中比较胶束白藜芦醇(mRVT)和纯白藜芦醇(RVT)的效果。通过T迷宫试验评估记忆表现。通过生化方法评估治疗对皮质和海马中特定神经递质水平及蛋白质表达的影响。我们的结果显示,聚合物胶束呈纳米级(约33nm),包封率达79%。mRVT治疗表现出更好的空间记忆保护作用。生化分析表明,10mg/kg剂量的mRVT在去甲肾上腺素神经传递和海马中乙酰胆碱酯酶抑制活性方面增强了纯药物的作用。此外,胶束白藜芦醇增加了大鼠皮质和海马中cAMP反应元件结合蛋白的表达以及Bcl2/BAX比值,这表明在实验性痴呆模型中具有抗凋亡作用。总之,我们的结果表明载有白藜芦醇的胶束系统在神经退行性疾病治疗中的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/378f/11641279/92a86ad95c8e/ijms-25-12777-g001.jpg

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