Hydroxy-safflor yellow A inhibits neuroinflammation mediated by Aβ1-42 in BV-2 cells
Hydroxy-safflor yellow A inhibits neuroinflammation mediated by Aβ1-42 in BV-2 cells
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羟基红花黄 A 抑制 BV-2 细胞中 A beta(1-42) 介导的神经炎症
DOI：
10.1016/j.neulet.2014.01.005
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发表时间：
2014-03-06
影响因子：
2.5
通讯作者：
Xu, Yun
中科院分区：
文献类型：
--
作者：
Zhang, Zuohui;Wu, Zhengzheng;Xu, Yun
炎症是阿尔茨海默病（AD）发展的一个重要因素。抗炎药物可能为 AD 提供有前景的治疗方法。羟基红花黄 A (HSYA) 是红花黄色素的化学成分，据报道具有有效的免疫抑制作用。本研究检查了 HSYA 在 A beta(1-42) 处理的 BV-2 小胶质细胞中的抗炎作用。实时荧光定量PCR检测IL-1β、IL-4、IL-10、TNF-α、COX-2、iNOS mRNA水平。 Western blotting检测COX-2、TNF-α、iNOS、Janus激酶2（JAK2）、p-JAK2、信号转导和转录激活因子3（STAT3）和p-STAT3的蛋白表达。采用BV2条件培养基处理SH-SY5Y细胞和原代神经元细胞进行间接毒性实验。分别使用 MTT 测定和膜联蛋白 V/PI 染色评估细胞活力和凋亡。结果表明，HSYA 显着降低促炎介质的表达并抑制 A beta(1-42) 诱导的神经炎症。此外，HSYA 保护原代皮质神经元和 SH-SY5Y 细胞免受小胶质细胞介导的神经毒性。 HSYA 还增强了 JAK2/STAT3 通路的磷酸化，AG 490 对 JAK2 的抑制减弱了 HSYA 的抗炎作用。总体而言，我们的研究结果表明，HSYA 抑制 A beta(1-42) 诱导的炎症，并部分通过 JAK2/STAT3 通路赋予神经保护作用，表明 HSYA 可能是治疗 AD 的潜在药物。 (C) 2014 Elsevier Ireland Ltd. 保留所有权利。
Inflammation is an important contributor to the development of Alzheimer's disease (AD). Anti-inflammatory medication may offer promising treatment for AD. Hydroxy-safflor yellow A (HSYA), a chemical component of the safflower yellow pigments, has been reported to exert potent immuno-suppressive effects. This study examined the anti-inflammatory effects of HSYA in A beta(1-42)-treated BV-2 microglia cells. The mRNA levels of IL-1 beta, IL-4, IL-10, TNF-alpha, COX-2 and iNOS were detected by real-time PCR. Western blotting was used to determine the protein expression of COX-2,TNF-alpha, iNOS, Janus Kinase 2 (JAK2), p-JAK2, signal transducers and activators of transcription 3 (STAT3) and p-STAT3.BV2-conditioned medium was used to treat SH-SY5Y cells and primary neuronal cells in indirect toxicity experiments. Cell viability and apoptosis were assessed using MTT assay and Annexin V/PI staining respectively. The results demonstrated that HSYA significantly reduced the expression of the pro-inflammatory mediators and inhibited A beta(1-42)-induced neuroinflammation. Moreover, HSYA protected primary cortical neurons and SH-SY5Y cells against microglia-mediated neurotoxicity. HSYA also enhanced the phosphorylation of JAK2/STAT3 pathway and inhibition of JAK2 by AG 490 attenuated the anti-inflammatory effects of HSYA. Overall, our findings suggested that HSYA inhibited A beta(1-42)-induced inflammation and conferred neuroprotection partially through JAK2/STAT3 pathway, indicating that HSYA could be a potential drug for the treatment of AD. (C) 2014 Elsevier Ireland Ltd. All rights reserved.