Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale Ferdinando Stagno D ׳Alcontres, 31, 98166, Messina, Italy.
Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale Ferdinando Stagno D ׳Alcontres, 31, 98166, Messina, Italy; Department of Pharmacological and Physiological Science, Saint Louis University, USA.
Neuropharmacology. 2020 Apr;166:107977. doi: 10.1016/j.neuropharm.2020.107977. Epub 2020 Jan 28.
Sodium propionate (SP) is one of the main short chain fatty acids (SCFA) that can be produced naturally through host metabolic pathways. SP have been documented and include the reduction of pro-inflammatory mediators in an in vivo model of colitis. The aim of this study is to evaluate the neuroprotective effects of SP in reducing inflammatory process associated to neurological disorders. We performed both in vitro model of Alzheimer's disease, induced by oligomeric Aβ stimulation, and in in vivo model of spinal cord injury (SCI) in which neuroinflammation plays a crucial role. For in vitro model, the human neuroblastoma SH-SY5Y cell line was first differentiated with retinoic acid (100 μM) for 24 h and then stimulated by oligomeric Aβ (1 μg/ml) and treated with SP at 0.1- 1-10 μM concentrations for another 24 h. Instead, the in vivo model of SCI was induced by extradural compression of the spinal cord at T6-T8 levels, and animals were treated with SP (10-30-100 mg/kg o.s) 1 and 6 h after SCI. Our results demonstrated that both in in vitro neuroinflammatory model and in vivo model of SCI the treatment with SP significantly reduced NF-κB nuclear translocation and IκBα degradation, as well as decreases COX-2 and iNOS expressions evaluated by Western blot analysis. Moreover, we showed that SP treatment significantly ameliorated histopathology changes and improved motor recovery in a dose-dependent manner. In conclusion, our results demonstrated that SP possesses neuroprotective effects, suggesting it could represent a target for therapeutic intervention in neuroinflammatory disorders.
丙酸钠（SP）是一种主要的短链脂肪酸（SCFA），可以通过宿主代谢途径自然产生。SP 已被证实可减少结肠炎的体内模型中的促炎介质。本研究旨在评估 SP 通过减少与神经紊乱相关的炎症过程的神经保护作用。我们进行了阿尔茨海默病的体外模型，该模型由寡聚体 Aβ 刺激诱导，以及在脊髓损伤（SCI）的体内模型中，神经炎症起着至关重要的作用。对于体外模型，首先用视黄酸（100 μM）将人神经母细胞瘤 SH-SY5Y 细胞系分化 24 小时，然后用寡聚体 Aβ（1 μg/ml）刺激，并在 0.1-1-10 μM 浓度下用 SP 处理 24 小时。相反，SCI 的体内模型通过 T6-T8 水平的硬膜外脊髓压迫诱导，并用 SP（10-30-100 mg/kg 口服）在 SCI 后 1 和 6 小时进行治疗。我们的结果表明，在体外神经炎症模型和 SCI 的体内模型中，SP 治疗均可显著降低 NF-κB 核易位和 IκBα 降解，以及通过 Western blot 分析评估的 COX-2 和 iNOS 表达。此外，我们表明 SP 治疗可显著改善组织病理学变化，并以剂量依赖的方式改善运动恢复。总之，我们的结果表明 SP 具有神经保护作用，表明它可能成为神经炎症性疾病治疗干预的靶点。
