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解析 α- 没药醇负载固体脂质纳米粒的抗细胞凋亡作用及其对神经-2a 细胞中 Aβ 诱导的神经毒性的影响。

Deciphering the anti-apoptotic potential of α-bisabolol loaded solid lipid nanoparticles against Aβ induced neurotoxicity in Neuro-2a cells.

机构信息

Department of Biotechnology, Alagappa University, Karaikudi, 630003, Tamil Nadu, India.

Department of Biotechnology, Alagappa University, Karaikudi, 630003, Tamil Nadu, India.

出版信息

Colloids Surf B Biointerfaces. 2020 Jun;190:110948. doi: 10.1016/j.colsurfb.2020.110948. Epub 2020 Mar 5.

Abstract

Nanoparticles based drug delivery system offers an alternative strategy to overcome several therapeutic limitations of various human ailments, particularly in age-linked Alzheimer's disease. Results of our previous cell-free studies indicated that α-bisabolol loaded solid lipid nanoparticles (ABS) significantly inhibited the aggregation of Aβ. The present study intended to evaluate the neuroprotective effect of ABS against Aβ induced toxicity in Neuro-2a cell lines. The results of in vitro cell line study revealed that pretreatment of Neuro-2a cell lines with ABS (5 & 10 μg/ml) significantly suppressed the production of free radicals such as reactive oxygen species (ROS)/reactive nitrogen species (RNS), and also augmented the ROS mediated macromolecular damages and loss of mitochondrial membrane potential induced by toxic Aβ peptide when compared to the standard drug donepezil (50 μg/ml). Moreover, reduced β-secretase, caspase-3, and cholinesterase activities were observed in the cells pretreated with ABS, which clearly evidenced the neuroprotective effect of ABS. Reduced expression of Bax and induced expression of Bcl-2 proteins observed through western blot analysis and live/dead cell viability analysis of Neuro-2a cells through confocal microscope further validated that ABS protects the cells from Aβ induced apoptosis. Taken together, the outcome of the present study signifies the neuroprotective effect of ABS against the Aβ induced toxicity in in vitro model of Neuro-2a cells.

摘要

基于纳米粒子的药物传递系统提供了一种替代策略,以克服各种人类疾病的许多治疗限制,特别是在与年龄相关的阿尔茨海默病中。我们之前的无细胞研究结果表明,α- 姜烯醇负载的固体脂质纳米颗粒(ABS)显著抑制了 Aβ 的聚集。本研究旨在评估 ABS 对 Aβ 诱导的 Neuro-2a 细胞系毒性的神经保护作用。体外细胞系研究的结果表明,与标准药物多奈哌齐(50 μg/ml)相比,ABS(5 和 10 μg/ml)预处理 Neuro-2a 细胞系可显著抑制自由基(如活性氧(ROS)/活性氮(RNS))的产生,并增强 ROS 介导的大分子损伤和线粒体膜电位丧失,由有毒 Aβ 肽引起。此外,在用 ABS 预处理的细胞中观察到 β- 分泌酶、半胱天冬酶-3 和胆碱酯酶活性降低,这清楚地证明了 ABS 的神经保护作用。通过 Western blot 分析观察到 Bax 表达降低和 Bcl-2 蛋白表达诱导,通过共聚焦显微镜对 Neuro-2a 细胞进行活/死细胞活力分析进一步验证了 ABS 可保护细胞免受 Aβ 诱导的细胞凋亡。综上所述,本研究的结果表明 ABS 对 Aβ 诱导的 Neuro-2a 细胞体外模型的毒性具有神经保护作用。

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