生物活性黄酮醇—漆黄素—通过负向调节NF-κB抑制过敏性气道炎症
2012/02/29
结果显示,漆黄素能以剂量依赖性方式抑制卵清蛋白诱导的支气管肺泡灌洗液总细胞计数、嗜酸性粒细胞计数的增加,IL-4、IL-5和IL-13水平也显著改善。漆黄素能抑制卵清蛋白诱导的肺组织嗜酸性粒细胞浸润和气道粘膜分泌、粘附分子、几丁质酶、IL-17、IL-33、Muc5ac和诱导型一氧化氮合酶的mRNA表达,以及抑制针对乙酰甲胆碱的气道高反应性。对卵清蛋白激发小鼠肺组织的核提取物分析显示,漆黄素能阻断NF-κB亚单位p65核转位和其DNA结合活性。对于正常人支气管上皮细胞,漆黄素能抑制TNF-α诱导的NF-κB依赖性报告基因表达。我们结果显示,漆黄素通过负向调节NF-κB信号通路,对哮喘具有一定的治疗作用。
(苏楠 审校)
Eur J Pharmacol. 2012 Jan 20. [Epub ahead of print]
Fisetin, a bioactive flavonol, attenuates allergic airway inflammation through negative regulation of NF-κB.
Goh FY, Upton N, Guan S, Cheng C, Shanmugam MK, Sethi G, Leung BP, Wong WS.
Source
Department of Pharmacology, Yong Loo Lin School of Medicine, National University Health System, Singapore.
Abstract
Persistent activation of nuclear factor-κB (NF-κB) has been associated with the development of asthma. Fisetin (3,7,3’,4’-tetrahydroxyflavone), a naturally occurring bioactive flavonol, has been shown to inhibit NF-κB activity. We hypothesized that fisetin may attenuate allergic asthma via negative regulation of the NF-κB activity. Female BALB/c mice sensitized and challenged with ovalbumin developed airway inflammation. Bronchoalveolar lavage fluid was assessed for total and differential cell counts, and cytokine and chemokine levels. Lung tissues were examined for cell infiltration and mucus hypersecretion, and the expression of inflammatory biomarkers. Airway hyperresponsiveness was monitored by direct airway resistance analysis. Fisetin dose-dependently inhibited ovalbumin-induced increases in total cell count, eosinophil count, and IL-4, IL-5 and IL-13 levels recovered in bronchoalveolar lavage fluid. It attenuated ovalbumin-induced lung tissue eosinophilia and airway mucus production, mRNA expression of adhesion molecules, chitinase, IL-17, IL-33, Muc5ac and inducible nitric oxide synthase in lung tissues, and airway hyperresponsiveness to methacholine. Fisetin blocked NF-κB subunit p65 nuclear translocation and DNA-binding activity in the nuclear extracts from lung tissues of ovalbumin-challenged mice. In normal human bronchial epithelial cells, fisetin repressed TNF-α-induced NF-κB-dependent reporter gene expression. Our findings implicate a potential therapeutic value of fisetin in the treatment of asthma through negative regulation of NF-κB pathway.
Eur J Pharmacol. 2012 Jan 20. [Epub ahead of print]
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鞘氨醇-1-磷酸类似物抑制反复过敏原暴露后的气道重构
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有和无阿司匹林过敏的哮喘患者,支气管阿司匹林激发试验中呼出气类花生酸类物质含量:初步研究