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

载有白藜芦醇的普卢兰尼克胶束可改善东莨菪碱引起的认知功能障碍,靶向乙酰胆碱酯酶活性和程序性细胞死亡

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

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.

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