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姜黄素通过抑制 NF-κB 减轻小鼠过敏性气道炎症和气道高反应性。

Curcumin attenuates allergic airway inflammation and hyper-responsiveness in mice through NF-κB inhibition.

机构信息

Central Research Institute, Choongwae Pharma Corp., Hwaseong, Republic of Korea.

出版信息

J Ethnopharmacol. 2011 Jul 14;136(3):414-21. doi: 10.1016/j.jep.2010.07.026. Epub 2010 Jul 17.

DOI:10.1016/j.jep.2010.07.026
PMID:20643202
Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

Curcumin, a polyphenol compound from Curcuma longa L. has been used for centuries as an anti-inflammatory remedy including asthma. Curcumin has been reported to exert an anti-inflammatory effect, in part, through inhibition of the NF-κB pathway.

AIM OF THE STUDY

The purposes of this study were to determine whether curcumin inhibits NF-κB-dependent transcription in vitro, and test whether treatment with curcumin reduces allergen-induced airway inflammation and hyper-responsiveness in a mouse model of asthma through inhibition of NF-κB pathway.

MATERIALS AND METHODS

The effect of curcumin on NF-κB transcriptional activity was investigated using a cell-based luciferase reporter assay in A549 cells and by measuring inhibitory κBα (IκBα), p65, and p50 levels after exposure of Raw264.7 cells to lipopolysaccharide (LPS). BALB/c mice were sensitized to ovalbumin (OVA) by intraperitoneal injection, and challenged with repeated exposure to aerosolized OVA. The effects of daily administered curcumin (200mg/kg body weight, i.p.) on airway hyper-responsiveness (AHR), inflammatory cell number, and IgE levels in bronchoalveolar lavage (BAL) fluid were analyzed. NF-κB activation in lung tissue was also assessed by Western blot analyses.

RESULTS

Curcumin inhibited NF-κB-dependent transcription in reporter assays in A549 cells with an IC(50) of 21.50±1.25μM. Curcumin stabilized IκBα and inhibited nuclear translocation of p65 and p50 in LPS-activated Raw264.7 cells, and curcumin-treated mice showed reduced nuclear translocation of p65 in lung tissue. Treatment with curcumin significantly attenuated AHR and reduced the numbers of total leukocytes and eosinophils in BAL fluid. Infiltration of inflammatory cells and mucus occlusions in lung tissue were significantly ameliorated by treatment with curcumin, which also markedly decreased the level of IgE in BAL fluid.

CONCLUSION

Curcumin attenuates the development of allergic airway inflammation and hyper-responsiveness, possibly through inhibition of NF-κB activation in the asthmatic lung tissue. Our results indicate that curcumin may attenuate development of asthma by inhibition of NF-κB activation.

摘要

民族药理学相关性

姜黄素是姜黄属植物中的一种多酚化合物,作为一种抗炎药物,其应用已有数百年历史,包括治疗哮喘。姜黄素具有抗炎作用,部分是通过抑制 NF-κB 途径来实现的。

研究目的

本研究旨在确定姜黄素是否能在体外抑制 NF-κB 依赖性转录,并通过抑制 NF-κB 途径,检测姜黄素治疗是否能减少变应原诱导的哮喘小鼠模型中的气道炎症和高反应性。

材料和方法

采用细胞荧光素酶报告基因法检测姜黄素对 A549 细胞 NF-κB 转录活性的影响,并用 LPS 处理 Raw264.7 细胞后检测抑制性κBα(IκBα)、p65 和 p50 的水平。BALB/c 小鼠经腹腔注射卵清蛋白(OVA)致敏,然后反复雾化 OVA 激发。分析每天腹腔注射 200mg/kg 体重姜黄素对气道高反应性(AHR)、支气管肺泡灌洗液(BAL)中炎性细胞数量和 IgE 水平的影响。通过 Western blot 分析评估肺组织中 NF-κB 的激活情况。

结果

姜黄素在 A549 细胞的报告基因检测中,对 NF-κB 依赖性转录的 IC50 为 21.50±1.25μM。姜黄素稳定 IκBα,抑制 LPS 激活的 Raw264.7 细胞中 p65 和 p50 的核转位,姜黄素治疗组小鼠肺组织中 p65 的核转位减少。姜黄素治疗可显著减轻 AHR,减少 BAL 液中总白细胞和嗜酸性粒细胞的数量。姜黄素治疗可显著改善炎症细胞浸润和肺组织中的黏液阻塞,同时显著降低 BAL 液中的 IgE 水平。

结论

姜黄素可减轻变应性气道炎症和高反应性的发展,可能是通过抑制哮喘肺组织中的 NF-κB 激活。我们的结果表明,姜黄素通过抑制 NF-κB 激活可能减轻哮喘的发展。

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