Licochalcone A Prevents the Loss of Dopaminergic Neurons by Inhibiting Microglial Activation in Lipopolysaccharide (LPS)-Induced Parkinson's Disease Models.
Licochalcone A Prevents the Loss of Dopaminergic Neurons by Inhibiting Microglial Activation in Lipopolysaccharide (LPS)-Induced Parkinson's Disease Models.
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DOI：
10.3390/ijms18102043
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发表时间：
2017-09-22
影响因子：
5.6
通讯作者：
Fu S
中科院分区：
文献类型：
--
作者：
Huang B;Liu J;Ju C;Yang D;Chen G;Xu S;Zeng Y;Yan X;Wang W;Liu D;Fu S
甘草黄酮A是从甘草中分离得到的一种黄酮类化合物，其对帕金森病(PD)的神经保护作用尚不清楚。帕金森病最显著的病理特征是多巴胺能神经元的丢失。激活的小胶质细胞诱导的神经炎症在多巴胺能神经退行性变中的关键作用已被证实。在本研究中，我们探讨了荔枝甲素对内毒素诱导的帕金森病模型的治疗作用。我们发现，LICO.A通过阻断BV-2细胞中细胞外信号调节激酶(ERK1/2)和核因子κB(NF-κB)p65的磷酸化，显著抑制内毒素刺激的促炎介质的产生和小胶质细胞的激活。此外，通过原代培养的中脑神经元-神经胶质细胞实验，我们证明了Lico.A可以减轻脂多糖诱导的帕金森病模型中[~3H]多巴胺(DA)摄取的减少和酪氨酸羟基酶免疫反应(TH-IR)神经元的丢失。此外，内毒素中毒可导致大鼠小胶质细胞活化、多巴胺能神经变性和明显的在体行为障碍。防止小胶质细胞激活和多巴胺能神经元减少，并改善帕金森病样行为损害。因此，这些结果首次证明了在帕金森病模型中，荔枝油A的神经保护作用与小胶质细胞和抗炎作用有关。
The neuroprotective effects of Licochalcone A (Lico.A), a flavonoid isolated from the herb licorice, in Parkinson’s disease (PD) have not been elucidated. The prominent pathological feature of PD is the loss of dopaminergic neurons. The crucial role of neuroinflammation induced by activated microglia in dopaminergic neurodegeneration has been validated. In this study, we explore the therapeutic effects of Lico.A in lipopolysaccharide (LPS)-induced PD models in vivo and in vitro. We find that Lico.A significantly inhibits LPS-stimulated production of pro-inflammatory mediators and microglial activation by blocking the phosphorylation of extracellular signal-regulated kinase (ERK1/2) and nuclear factor κB (NF-κB) p65 in BV-2 cells. In addition, through cultured primary mesencephalic neuron-glia cell experiments, we illustrate that Lico.A attenuates the decrease in [3H] dopamine (DA) uptake and the loss of tyrosine hydroxylase-immunoreactive (TH-ir) neurons in LPS-induced PD models in vitro. Furthermore, LPS intoxication in rats results in microglial activation, dopaminergic neurodegeneration and significant behavioral deficits in vivo. Lico.A treatment prevents microglial activation and reduction of dopaminergic neuron and ameliorates PD-like behavioral impairments. Thus, these results demonstrate for the first time that the neuroprotective effects of Lico.A are associated with microglia and anti-inflammatory effects in PD models.
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