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负载磺丁基醚-β-环糊精的姜黄素纳米载体通过下调 NLRP3/Caspase-1 信号通路抑制 APP/PS1 双转基因 AD 模型小鼠海马神经元炎症损伤

Neurotherapeutic efficacy of loaded sulforaphane on iron oxide nanoparticles against cuprizone-induced neurotoxicity: role of MMP-9 and S100β.

机构信息

Department of Therapeutic Chemistry, Pharmaceutical and Drug Industries Research Institute, National Research Centre, Cairo, Egypt.

Refractories, Ceramics and Building Materials Department, Advanced Materials, Technology and Mineral Resources Research Institute, National Research Centre, Cairo, Egypt.

出版信息

Toxicol Mech Methods. 2023 Nov;33(6):463-479. doi: 10.1080/15376516.2023.2177219. Epub 2023 Feb 12.

DOI:10.1080/15376516.2023.2177219
PMID:36775846
Abstract

Cuprizone (CUP) induces neurotoxicity and demyelination in animal models by provoking the activation of glial cells and the generation of reactive oxygen species (ROS). Sulforaphane (SF) is a phytochemical that exhibits a neuroprotective potential. In this study, we investigated the neurotherapeutic and pro-remyelinating activities of SF and SF-loaded within iron oxide nanoparticles (IONP-SF) in CUP-exposed rats. Magnetite iron oxide nanoparticles (IONPs) were prepared using the hydrothermal method that was further loaded with SF (IONP-SF). The loading of SF within the magnetite nanoparticles was assessed using FTIR, TEM, DLS, Zetasizer, and XPS. For the investigations, adult male Wistar rats ( = 40) were administrated either on a regular diet or a diet with CUP (0.2%) for 5 weeks. The rats were divided into four groups: negative control, CUP-induced, CUP + SF, and CUP + IONP-SF. CUP-exposed brains exhibited a marked elevation in lipid peroxidation, along with a significant decrease in the activities of glutathione peroxidase (GPx), and catalase (CAT). In addition, CUP intoxication downregulated the expression of myelin basic protein (MBP) and myelin proteolipid protein (PLP), upregulated the expression of Matrix metallopeptidase-9 (MMP-9) and S100β, and increased caspase-3 immunoexpression, these results were supported histopathologically in the cerebral cortexes. Treatment of CUP-rats with either SF or IONP-SF demonstrated remyelinating and neurotherapeutic activities. We could conclude that IONP-SF was more effective than free SF in mitigating the CUP-induced downregulation of MBP, upregulation of S100β, and caspase-3 immunoexpression.

摘要

杯状醇(CUP)通过激活神经胶质细胞和产生活性氧(ROS)在动物模型中引起神经毒性和脱髓鞘。萝卜硫素(SF)是一种具有神经保护潜力的植物化学物质。在这项研究中,我们研究了 SF 及其负载在氧化铁纳米粒子(IONP-SF)中的神经治疗和促髓鞘形成活性在暴露于 CUP 的大鼠中的作用。通过水热法制备了磁铁氧化铁纳米粒子(IONPs),然后进一步负载 SF(IONP-SF)。通过 FTIR、TEM、DLS、Zetasizer 和 XPS 评估 SF 在磁铁纳米粒子中的负载情况。在研究中,成年雄性 Wistar 大鼠( = 40)被给予正常饮食或含 CUP(0.2%)的饮食 5 周。大鼠分为四组:阴性对照组、CUP 诱导组、CUP+SF 组和 CUP+IONP-SF 组。暴露于 CUP 的大脑表现出脂质过氧化的明显升高,同时谷胱甘肽过氧化物酶(GPx)和过氧化氢酶(CAT)的活性显著降低。此外,CUP 中毒下调了髓鞘碱性蛋白(MBP)和髓鞘少突胶质细胞糖蛋白(PLP)的表达,上调了基质金属蛋白酶-9(MMP-9)和 S100β的表达,并增加了 caspase-3 免疫表达,这些结果在大脑皮层的组织病理学上得到了支持。用 SF 或 IONP-SF 治疗 CUP 大鼠表现出髓鞘形成和神经治疗活性。我们可以得出结论,与游离 SF 相比,IONP-SF 更能减轻 CUP 诱导的 MBP 下调、S100β 上调和 caspase-3 免疫表达。

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