Preventive and curative glycoside kaempferol treatments attenuate the TH2-driven allergic airway disease
Preventive and curative glycoside kaempferol treatments attenuate the TH2-driven allergic airway disease
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DOI：
10.1016/j.intimp.2009.09.005
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发表时间：
2009-12-01
影响因子：
5.6
通讯作者：
Russo, M.
中科院分区：
文献类型：
--
作者：
Medeiros, K. C. P.;Faustino, L.;Russo, M.
哮喘是一种以气道炎症和气道高反应性（AHR）为特征的慢性呼吸道疾病。治疗过敏性疾病的一个策略是开发新药。黄酮类化合物是从植物中提取的化合物，具有抗过敏、抗炎和抗氧化的特性。在哮喘实验模型中，研究类黄酮山奈酚糖苷3-O-[β - d -糖- iranosil-(1 - bbb6)- α - l- ramnopiranol]-7- o - α - l- ramnopiransil -山奈酚（GRRK）是否能够作为预防（GRRK P）或治疗（GRRK C）治疗调节变应性气道疾病（AAD）。每隔一周，BALB/c小鼠被皮下（sc）致敏两次卵清蛋白(OVA)/明矾，并被鼻内注射两次OVA。为了评估任何预防作用，在每次OVA致敏和攻击前1小时给予GRRK，而为了分析疗效，小鼠首先用OVA致敏，然后在第18至21天给予GRRK。最后一次攻卵24 h后评估AAD的发病情况。两种治疗均导致支气管肺泡灌洗液（BAL）中总白细胞和嗜酸性粒细胞计数的剂量依赖性降低。GRRK还能降低BAL细胞CD4（+）、B220（+）、MHC II类和CD40分子的表达。组织学和肺力学结果表明，GRRK抑制了黏液的产生，改善了虫卵攻击引起的AHR。此外，GRRK破坏了Th2细胞因子（IL-5和IL-13）的产生，并没有诱导Th1型炎症。这些发现表明，在确定过敏性肺病之前或之后，GRRK治疗可下调关键的哮喘特征。因此。GRRK具有治疗过敏性哮喘的潜在临床应用价值。(C) 2009 Elsevier B.V.版权所有
Asthma is a chronic respiratory disease characterized by airway inflammation and airway hyperresponsiveness (AHR). One strategy to treat allergic diseases is the development of new drugs. Flavonoids are compounds derived from plants and are known to have antiallergic, anti-inflammatory, and antioxidant properties. To investigate whether the flavonoid kaempferol glycoside 3-O-[beta-D-glycopiranosil-(1 -> 6)-alpha-L-ramnopiranosil]-7-O-alpha-L-ramnopiranosil-kaempferol (GRRK) would be capable of modulating allergic airway disease (AAD) either as a preventive (GRRK P) or curative (GRRK C) treatment in an experimental model of asthma. At weekly intervals, BALB/c mice were subcutaneously (sc) sensitized twice with ovalbumin (OVA)/alum and challenged twice with OVA administered intranasally. To evaluate any preventive effects GRRK was administered 1 h (hour) before each OVA-sensitization and challenge, while to analyze the curative effects mice were first sensitized with OVA, followed by GRRK given at day 18 through 21. The onset: of AAD was evaluated 24 h after the last OVA challenge. Both treatments resulted in a dose-dependent reduction in total leukocyte and eosinophil counts in the bronchoalveolar lavage fluid (BAL). GRRK also decreased CD4(+), B220(+), MHC class II and CD40 molecule expressions in BAL cells. Histology and lung mechanic showed that GRRK suppressed mucus production and ameliorated the AHR induced by OVA challenge. Furthermore, GRRK impaired Th2 cytokine production (IL-5 and IL-13) and did not induce a Th1 pattern of inflammation. These findings demonstrate that GRRK treatment before or after established allergic lung disease down-regulates key asthmatic features. Therefore. GRRK has a potential clinical use for the treatment of allergic asthma. (C) 2009 Elsevier B.V. All rights reserved.