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载百里香酚的硒纳米颗粒对体外帕金森病模型中6-羟基多巴胺诱导的细胞凋亡和氧化应激的神经保护作用

Neuroprotective Effects of Thymol-Loaded Selenium Nanoparticles Against 6-OHDA-Induced Apoptosis and Oxidative Stress in an In Vitro Parkinson's Disease Model.

作者信息

Abbasinezhad-Moud Farzaneh, Shirazinia Matin, Mirzabeyki Raheleh, Einafshar Elham, Alavi Mohaddeseh Sadat, Shaban Sayeh, Gheibi Elaheh, Bahrami Afsane

机构信息

Department of Medical Biochemistry, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

出版信息

Curr Pharm Des. 2025 Jul 16. doi: 10.2174/0113816128380006250630103711.

DOI:10.2174/0113816128380006250630103711
PMID:40676804
Abstract

INTRODUCTION

Parkinson's disease (PD) is characterized by the degeneration of dopaminergic neurons within the substantia nigra, leading to progressive motor dysfunction. There are still limited diseasemodifying options that counteract the process of disease progression. This study aimed to evaluate the neuroprotective effects of thymol, both in its free form and when loaded onto selenium nanoparticles (SeNPs), in a 6-hydroxydopamine (6-OHDA)-induced PD model using SH-SY5Y cells.

METHOD

SeNPs were synthesized using a chemical reduction method with ascorbic acid, achieving a 68% entrapment efficiency for thymol. FTIR analysis suggested an interaction between thymol and selenium, which was confirmed by EDX analysis. Nano-Se-thymol particles were observed to be spherical, with a mean size of 135.7 nm and a negative surface charge.

RESULTS

Nano-Se-thymol exhibited low toxicity in normal fibroblast cells and demonstrated greater neuroprotective effects against 6-OHDA-induced cytotoxicity compared to thymol. Nano-Se-thymol significantly reduced ROS generation and increased cell viability compared to 6-OHDA. Furthermore, Nano-Se-thymol decreased the expression of NF-κB inflammatory markers and caspase-3 apoptotic proteins, which were elevated by 6-OHDA, compared to thymol alone.

DISCUSSION

Nano-Se-Thymol significantly attenuates 6-OHDA-induced cytotoxicity in an established in vitro model of PD. The neuroprotective efficacy of Nano-Se-Thymol is attributed to its enhanced antioxidant capacity, as evidenced by a significant reduction in ROS levels, along with its ability to inhibit apoptosis and modulate cell cycle progression.

CONCLUSIONS

Nano-Se-thymol is a potential disease-modifying agent for the treatment of PD; however, further studies and long-term safety assessments are essential to confirm these benefits and understand the underlying mechanisms.

摘要

引言

帕金森病(PD)的特征是黑质内多巴胺能神经元变性,导致进行性运动功能障碍。目前对抗疾病进展过程的疾病修饰疗法仍然有限。本研究旨在评估百里酚及其负载于硒纳米颗粒(SeNPs)上时,在6-羟基多巴胺(6-OHDA)诱导的PD模型中对SH-SY5Y细胞的神经保护作用。

方法

采用化学还原法用抗坏血酸合成SeNPs,百里酚的包封率达到68%。傅里叶变换红外光谱(FTIR)分析表明百里酚与硒之间存在相互作用,能量色散X射线光谱(EDX)分析证实了这一点。观察到纳米硒-百里酚颗粒呈球形,平均粒径为135.7 nm,表面带负电荷。

结果

纳米硒-百里酚在正常成纤维细胞中表现出低毒性,与百里酚相比,对6-OHDA诱导的细胞毒性具有更强的神经保护作用。与6-OHDA相比,纳米硒-百里酚显著降低活性氧(ROS)生成并提高细胞活力。此外,与单独的百里酚相比,纳米硒-百里酚降低了6-OHDA升高的核因子κB(NF-κB)炎症标志物和半胱天冬酶-3凋亡蛋白的表达。

讨论

在已建立的PD体外模型中,纳米硒-百里酚显著减轻6-OHDA诱导的细胞毒性。纳米硒-百里酚的神经保护功效归因于其增强的抗氧化能力,这表现为ROS水平显著降低,以及其抑制细胞凋亡和调节细胞周期进程的能力。

结论

纳米硒-百里酚是一种潜在的用于治疗PD的疾病修饰剂;然而,需要进一步研究和长期安全性评估来证实这些益处并了解其潜在机制。

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