College of Animal Science and Veterinary Medicine, Jilin University, Changchun 130062, China.
Int J Mol Sci. 2018 Jul 31;19(8):2242. doi: 10.3390/ijms19082242.
Parkinson's disease (PD), a frequent degenerative disease in the elderly, is characterized by dopaminergic neurodegeneration in the substantia nigra pars compacta (SNpc). Neuroinflammation caused by over-activated microglia plays a crucial role in the pathogenesis of PD. Tubeimoside I (TBMS1) has a broad anti-inflammatory effect in peripheral tissues, but the effect on neuroinflammation has not been reported. Therefore, we explored whether TBMS1 could protect dopaminergic neurons by inhibiting the activation of microglia in lipopolysaccharide (LPS)-induced PD rat model. In addition, then, the effect and mechanism of TBMS1 on neuroinflammation were assessed in LPS-exposed murine microglial BV-2 cells. The results in vivo showed that TBMS1 suppressed microglial activation and dopaminergic neurons' reduction in LPS-injected PD rat model. In vitro study found that TBMS1 could inhibit LPS-induced inflammatory responses in BV-2 cells, and this effect was mediated by suppressing the phosphorylation of protein kinase B (AKT), nuclear factor-kappa B (NF-κB p65), p38 and extracellular regulated protein kinases (ERK1/2). Taken together, these results demonstrated for the first time that TBMS1 played a role in protecting dopaminergic neurons by inhibiting neuroinflammation mediated by microglia.
帕金森病（PD）是一种常见的老年退行性疾病，其特征是黑质致密部（SNpc）中的多巴胺能神经元变性。由过度激活的小胶质细胞引起的神经炎症在 PD 的发病机制中起着关键作用。 葫芦素 I（TBMS1）在周围组织中具有广泛的抗炎作用，但尚未报道其对神经炎症的作用。因此，我们探讨了 TBMS1 是否可以通过抑制脂多糖（LPS）诱导的 PD 大鼠模型中小胶质细胞的激活来保护多巴胺能神经元。此外，我们评估了 TBMS1 对 LPS 暴露的鼠小胶质细胞 BV-2 细胞中神经炎症的作用和机制。体内研究结果表明，TBMS1 抑制了 LPS 注射 PD 大鼠模型中小胶质细胞的激活和多巴胺能神经元的减少。体外研究发现，TBMS1 可以抑制 LPS 诱导的 BV-2 细胞中的炎症反应，这种作用是通过抑制蛋白激酶 B（AKT）、核因子-κB p65（NF-κB p65）、p38 和细胞外调节蛋白激酶（ERK1/2）的磷酸化来介导的。综上所述，这些结果首次表明，TBMS1 通过抑制小胶质细胞介导的神经炎症在保护多巴胺能神经元中发挥作用。
