Department of Neurology, The Affiliated Nanhua Hospital, Hengyang Medical School, University of South China, 421001 Hengyang, Hunan, China.
Department of Intensive Care Unit, The Affiliated Nanhua Hospital, Hengyang Medical School, University of South China, 421001 Hengyang, Hunan, China.
J Integr Neurosci. 2024 Sep 30;23(10):185. doi: 10.31083/j.jin2310185.
Luteolin is a natural flavonoid and its neuroprotective and anti-inflammatory effects have been confirmed to mitigate neurodegeneration. Despite these findings, the underlying mechanisms responsible for these effects remain unclear. Toll-like receptor 4 (TLR4) is widely distributed in microglia and plays a pivotal role in neuroinflammation and neurodegeneration. Here studies are outlined that aimed at determining the mechanisms responsible for the anti-inflammatory and neuroprotective actions of luteolin using a rodent model of Parkinson's disease (PD) and specifically focusing on the role of TLR4 in this process.
The mouse model of PD used in this experiment was established through a single injection of lipopolysaccharide (LPS). Mice were then subsequently randomly allocated to either the luteolin or vehicle-treated group, then motor performance and dopaminergic neuronal injury were evaluated. BV2 microglial cells were treated with luteolin or vehicle saline prior to LPS challenge. MRNA expression of microglial specific marker ionized calcium-binding adapter molecule 1 () and M1/M2 polarization markers, as well as the abundance of indicated pro-inflammatory cytokines in the mesencephalic tissue and BV2 were quantified by real time-polymerase chain reaction (RT-PCR) and Enzyme-linked Immunosorbent Assay (ELISA), respectively. Cell viability and apoptosis of neuron-like PC12 cell line co-cultured with BV2 were detected. TLR4 RNA transcript and protein abundance in mesencephalic tissue and BV2 cells were detected. Nuclear factor kappa-gene binding (NF-κB) p65 subunit phosphorylation both and was evaluated by immunoblotting.
Luteolin treatment induced functional improvements and alleviated dopaminergic neuronal loss in the PD model. Luteolin inhibited apoptosis and promoted cell survival in PC12 cells. Luteolin treatment shifted microglial M1/M2 polarization towards an anti-inflammatory M2 phenotype both . Finally, it was found that luteolin treatment significantly downregulated both mRNA and protein expression as well as restraining NF-κB p65 subunit phosphorylation.
Luteolin restrained dopaminergic degeneration and by blocking TLR4-mediated neuroinflammation.
木犀草素是一种天然黄酮类化合物，其神经保护和抗炎作用已被证实可减轻神经退行性变。尽管有这些发现，但导致这些作用的潜在机制仍不清楚。 Toll 样受体 4（TLR4）广泛分布于小胶质细胞中，在神经炎症和神经退行性变中起关键作用。在这里，研究概述了使用帕金森病（PD）的啮齿动物模型确定木樨草素抗炎和神经保护作用的机制，特别是侧重于 TLR4 在该过程中的作用。
本实验中使用的 PD 小鼠模型是通过单次注射脂多糖（LPS）建立的。然后，将小鼠随机分配到木樨草素或载体处理组，然后评估运动表现和多巴胺能神经元损伤。用木樨草素或载体生理盐水处理 BV2 小胶质细胞，然后用 LPS 进行挑战。通过实时聚合酶链反应（RT-PCR）和酶联免疫吸附测定（ELISA）分别定量小胶质细胞特异性标记物离子钙结合接头分子 1（）和 M1/M2 极化标记物以及中脑组织和 BV2 中指示性促炎细胞因子的丰度。检测与 BV2 共培养的神经元样 PC12 细胞系的细胞活力和细胞凋亡。检测中脑组织和 BV2 细胞中 TLR4 RNA 转录物和蛋白丰度。通过免疫印迹评估核因子 kappa-基因结合（NF-κB）p65 亚基磷酸化和。
木樨草素治疗可诱导 PD 模型的功能改善并减轻多巴胺能神经元丢失。木樨草素抑制 PC12 细胞的凋亡并促进细胞存活。木樨草素治疗使小胶质细胞 M1/M2 极化向抗炎 M2 表型转变。最后发现，木樨草素治疗显著下调和的 mRNA 和蛋白表达，并抑制 NF-κB p65 亚基磷酸化。
木樨草素通过阻断 TLR4 介导的神经炎症来抑制多巴胺能变性和。
