Beta-naphthoflavone inhibits LPS-induced inflammation in BV-2 cells via AKT/Nrf-2/HO-1-NF-κB signaling axis
Beta-naphthoflavone inhibits LPS-induced inflammation in BV-2 cells via AKT/Nrf-2/HO-1-NF-κB signaling axis
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DOI：
10.1016/j.imbio.2020.151965
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发表时间：
2020-07-01
期刊：
影响因子：
2.8
通讯作者：
Fu, Shoupeng
中科院分区：
文献类型：
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作者：
Gao, Xiyu;He, Dewei;Fu, Shoupeng
大量研究表明，小胶质细胞过度激活可引起神经炎症，释放促炎介质，从而导致神经退行性疾病，如帕金森病、阿尔茨海默病等。β -萘黄酮（BNF）在交界组织中具有抗氧化和抗炎作用，但与神经炎症相关的作用尚未见报道。因此，本实验的目的是探讨BNF对神经炎症的影响及其机制。结果表明，BNF显著抑制lps暴露的BV-2细胞促炎介质(诱导型一氧化氮合酶（iNOS）、环氧合酶-2 （COX-2）、肿瘤坏死因子- α （tnf - α)和白细胞介素-6 (IL-6)）的产生。western blot结果分析发现，BNF可加速AKT/Nrf-2/HO-1信号通路的激活，抑制NF-kappa B通路的激活。进一步研究表明，BNF通过促进HO-1抑制NF-kappa B通路的激活，而HO-1抑制剂SnPP IX可抑制BNF的抗炎功能。我们还发现，BNF通过抑制lps暴露的BV2细胞中炎症介质的释放，降低了人神经母细胞瘤细胞（SHSY5Y）和小鼠海马神经元细胞系（HT22）的凋亡率。综上所述，我们的研究结果表明，BNF可以通过BV2细胞的AKT/Nrf-2/HO-1-NF-kappa B信号轴抑制炎症反应，并通过抑制BV2细胞的活化发挥神经保护作用。
Numerous studies have shown that over-activation of microglia could cause neuroinflammation and release proinflammatory mediators, which could result in neurodegenerative diseases, like Parkinson's disease, Alzheimer's disease etc. Beta-naphthoflavone (BNF) has anti-oxidant and anti-inflammatory effects in borderline tissues, but BNF has not been reported the effect associated with neuroinflammation. Therefore, the purpose of this experiment is to inquiry the impact and mechanism of BNF on neuroinflammation. The results indicated that BNF significantly inhibited the production of pro-inflammatory mediators (inducible nitric-oxide synthase (iNOS), Cyclooxygenase-2 (COX-2), tumor necrosis factor-alpha (TNF-alpha) andinterleukin-6 (IL-6)) in LPS-exposed BV-2 cells. Analysis of western blot results found that BNF accelerated the activation of AKT/Nrf-2/HO-1 signaling pathway and suppressed NF-kappa B pathway activation. Further study showed that BNF inhibited activation of NF-kappa B pathway via promoting HO-1, and SnPP IX (a HO-1 inhibitor) could inhibit anti-inflammatory function of BNF. We also found that BNF reduced the apoptosis rate of Human neuroblastoma cells (SHSY5Y) and mouse hippocampal neuron cell line (HT22) by inhibiting release of inflammatory mediators in LPS-exposed BV2 cells. In a word, our results suggested that BNF could inhibit inflammatory response via AKT/Nrf-2/HO-1-NF-kappa B signaling axis in BV2 cells and exerts neuroprotective impact via inhibiting the activation of BV2 cells.