Immunosuppressive Effects of Fisetin in Ovalbumin-Induced Asthma through Inhibition of NF-κB Activity

Immunosuppressive Effects of Fisetin in Ovalbumin-Induced Asthma through Inhibition of NF-κB Activity
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DOI:
10.1021/jf202756f
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发表时间:
2011-10-12
影响因子:
6.1
通讯作者:
Fu, Shu-Ling
Fu, Shu-Ling
中科院分区:
农林科学1区
文献类型:
--
作者:
Wu, Mei-Yao;Hung, Shih-Kai;Fu, Shu-Ling

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非瑟酮是一种常见于水果和蔬菜中的类黄酮化合物,可以通过抑制NF-κ B信号通路发挥抗炎活性。本研究旨在评价非瑟酮的抗哮喘活性并探讨其可能的分子机制。我们发现,非瑟酮减弱了卵白蛋白诱导的哮喘中的肺部炎症、杯状细胞增生和气道高反应性,并降低了支气管肺泡灌洗液中的嗜酸性粒细胞和淋巴细胞。非瑟酮治疗降低了肺中过敏性气道炎症的关键起始物(嗜酸细胞活化趋化因子-1和TSLP)、Th 2相关细胞因子(IL-4、IL-5和IL-13)以及胸淋巴结细胞和脾细胞中Th 2主导转录因子加塔-3和细胞因子的表达。值得注意的是,非瑟酮处理损害了OVA刺激的肺组织和TNF-α刺激的支气管上皮细胞中的NF-κ B活化。总的来说,这项研究证明了非瑟酮在改善哮喘表型方面的有益作用。非瑟酮的抗哮喘活性与减少Th 2应答以及抑制NF-κ B及其下游趋化因子有关。
Fisetin, a flavonoid compound commonly present in fruits and vegetables, can exert anti-inflammation activities via inhibition of the NF-kappa B-signaling pathway. This study aims to evaluate the antiasthma activity of fisetin and investigate its possible molecular mechanisms. We found that fisetin attenuated lung inflammation, goblet cell hyperplasia, and airway hyperresponsiveness in ovalbumin-induced asthma and decreased eosinophils and lymphocytes in bronchoalveolar lavage fluid. Fisetin treatment reduced expression of the key initiators of allergic airway inflammation (eotaxin-1 and TSLP), Th2-associated cytokines (IL-4, IL-5, and IL-13) in lungs, and Th2-predominant transcription factor GATA-3 and cytokines in thoracic lymph node cells and splenocytes. Notably, fisetin treatment impaired NF-kappa B activation in OVA-stimulated lung tissues and TNF-alpha-stimulated bronchial epithelial cells. Collectively, this study demonstrated the beneficial effect of fisetin in the amelioration of asthmatic phenotypes. The antiasthma activity of fisetin is associated with reduction of Th2 responses as well as suppression of NF-kappa B and its downstream chemokines.