A Novel Antiinflammatory Role for Andrographolide in Asthma via Inhibition of the Nuclear Factor-κB Pathway
A Novel Antiinflammatory Role for Andrographolide in Asthma via Inhibition of the Nuclear Factor-κB Pathway
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DOI：
10.1164/rccm.200809-1516oc
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发表时间：
2009-04-15
影响因子：
24.7
通讯作者：
Wong, W. S. Fred
中科院分区：
文献类型：
--
作者：
Bao, Zhang;Guan, Shouping;Wong, W. S. Fred
理由：核因子- κ B的持续激活与哮喘的发生有关。穿心莲内酯是药用植物穿心莲的主要活性成分，具有抑制nf - κ B活性的作用。目的：我们假设穿心术可能通过抑制nf - κ B信号通路来减轻过敏性哮喘。方法：BALB/c小鼠致敏，卵清蛋白（OVA）致敏，引起气道炎症。评估支气管肺泡灌洗液的总细胞和分化细胞计数、细胞因子和趋化因子水平。同时测定血清IgE水平。检测肺组织细胞浸润、粘液分泌、炎症生物标志物的表达。直接气道阻力分析监测气道高反应性。测量和主要结果：穿心莲内酯剂量依赖性地抑制ova诱导的支气管肺泡灌洗液中总细胞计数、嗜酸性粒细胞计数和IL-4、IL-5、IL-13水平的增加，并降低ova特异性IgE水平。它能减弱va诱导的肺组织嗜酸性粒细胞增多和气道粘液生成，降低肺组织中e -选择素、几丁质酶、Muc5ac和诱导型一氧化氮合酶mRNA的表达，降低气道对甲胆碱的高反应性。在正常人支气管上皮细胞中，穿心针可阻断肿瘤坏死因子α诱导的抑制性kappa B激酶β磷酸化，抑制下游kappa B α降解、p65亚基NF-kappa B磷酸化，以及p65核易位和dna结合活性。同样地，穿心莲可阻断ova小鼠肺组织核提取物的p65核易位和dna结合活性。结论：我们的研究结果提示穿心术在治疗哮喘方面具有潜在的治疗价值，它可能通过抑制κ B激酶β激活水平抑制nf - κ B通路起作用。
Rationale Persistent activation of nuclear factor (NF)-kappa B has been associated with the development of asthma. Andrographolide, the principal active component of the medicinal plant Andrographis paniculata, has been shown to inhibit NF-kappa B activity.Objectives: We hypothesized that andrographolicle may attenuate allergic asthma via inhibition of the NF-kappa B signaling pathway.Methods: BALB/c mice sensitized and challenged with ovalbumin (OVA) developed airway inflammation. Bronchoalveolar lavage fluid was assessed for total and differential cell counts, and cytokine and chemokine levels. Serum IgE levels were also determined. 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.Measurements and Main Results: Andrographolide dose-dependently inhibited OVA-induced increases in total cell count, eosinophil count, and IL-4, IL-5, and IL-13 levels recovered in bronchoalveolar lavage fluid, and reduced serum level of OVA-specific IgE. It attenuated OVA-induced lung tissue eosinophilia and airway mucus production, mRNA expression of E-selectin, chitinases, Muc5ac, and inducible nitric oxide synthase in lung tissues, and airway hyperresponsiveness to methacholine. In normal human bronchial epithelial cells, andrographolicle blocked tumor necrosis factor-alpha-induced phosphorylation of inhibitory kappa B kinase-beta, and downstream inhibitory kappa B alpha degradation, p65 subunit of NF-kappa B phosphorylation, and p65 nuclear translocation and DNA-binding activity. Similarly, andrographolicle blocked p65 nuclear translocation and DNA-binding activity in the nuclear extracts from lung tissues of OVA-challenged mice.Conclusions: Our findings implicate a potential therapeutic value of andrographolicle in the treatment of asthma and it may act by inhibiting the NF-kappa B pathway at the level of inhibitory kappa B kinase-beta activation.