穿心莲内酯通过抑制NF-κB途径抑制哮喘发生
2009/05/18
穿心莲内酯是植物穿心莲中提取的主要活性成分，具有清热解毒、凉血消肿的作用，传统主要用于上呼吸道感染。而在该研究中，Bao Z等观察了穿心莲内酯对哮喘的抑制作用及其机制。该研究采用BALB/c小鼠，通过OVA致敏激发建立哮喘模型，观察肺泡灌洗液（BALF）中细胞总数和分类计数，细胞因子和趋化因子水平，血清IgE水平，肺组织炎症细胞浸润和黏液分泌情况，以及气道反应性变化。
结果：穿心莲内酯可降低哮喘小鼠BALF中细胞总数、嗜酸性粒细胞数，降低BALF中IL-4、IL-5、IL-13水平，降低血清IgE水平，降低OVA致敏激发所致的肺组织嗜酸性粒细胞浸润和黏液分泌，抑制气道高反应性。肺组织表达E-选择蛋白、chitinases, Muc5ac、和诱生型一氧化氮合酶的mRNA水平下降。同时通过体外气道上皮培养和体内研究发现，穿心莲内酯可阻断NF-κB亚单位P65磷酸化、核转位和DNA结合活性。因此作者认为穿心莲内酯可通过NF-κB途径抑制哮喘发生。
(王苹莉 浙江医科大学附属第二医院呼吸科 310009 摘译)
（Am J Respir Crit Care Med. 2009 Apr 15;179(8):657-665）
novel antiinflammatory role for andrographolide in asthma via inhibition of the nuclear factor-kappaB pathway.
Bao Z, Guan S, Cheng C, Wu S, Wong SH, Kemeny DM, Leung BP, Wong WSA
Am J Respir Crit Care Med. 2009 Apr 15;179(8):657-65.
RATIONALE: Persistent activation of nuclear factor (NF)-kappaB 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-kappaB activity.
OBJECTIVES: We hypothesized that andrographolide may attenuate allergic asthma via inhibition of the NF-kappaB 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, andrographolide blocked tumor necrosis factor-alpha-induced phosphorylation of inhibitory kappaB kinase-beta, and downstream inhibitory kappaB alpha degradation, p65 subunit of NF-kappaB phosphorylation, and p65 nuclear translocation and DNA-binding activity. Similarly, andrographolide 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 andrographolide in the treatment of asthma and it may act by inhibiting the NF-kappaB pathway at the level of inhibitory kappaB kinase-beta activation.
结果：穿心莲内酯可降低哮喘小鼠BALF中细胞总数、嗜酸性粒细胞数，降低BALF中IL-4、IL-5、IL-13水平，降低血清IgE水平，降低OVA致敏激发所致的肺组织嗜酸性粒细胞浸润和黏液分泌，抑制气道高反应性。肺组织表达E-选择蛋白、chitinases, Muc5ac、和诱生型一氧化氮合酶的mRNA水平下降。同时通过体外气道上皮培养和体内研究发现，穿心莲内酯可阻断NF-κB亚单位P65磷酸化、核转位和DNA结合活性。因此作者认为穿心莲内酯可通过NF-κB途径抑制哮喘发生。
(王苹莉 浙江医科大学附属第二医院呼吸科 310009 摘译)
（Am J Respir Crit Care Med. 2009 Apr 15;179(8):657-665）
novel antiinflammatory role for andrographolide in asthma via inhibition of the nuclear factor-kappaB pathway.
Bao Z, Guan S, Cheng C, Wu S, Wong SH, Kemeny DM, Leung BP, Wong WSA
Am J Respir Crit Care Med. 2009 Apr 15;179(8):657-65.
RATIONALE: Persistent activation of nuclear factor (NF)-kappaB 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-kappaB activity.
OBJECTIVES: We hypothesized that andrographolide may attenuate allergic asthma via inhibition of the NF-kappaB 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, andrographolide blocked tumor necrosis factor-alpha-induced phosphorylation of inhibitory kappaB kinase-beta, and downstream inhibitory kappaB alpha degradation, p65 subunit of NF-kappaB phosphorylation, and p65 nuclear translocation and DNA-binding activity. Similarly, andrographolide 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 andrographolide in the treatment of asthma and it may act by inhibiting the NF-kappaB pathway at the level of inhibitory kappaB kinase-beta activation.
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哮喘患者的蛋白质微阵列分析
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游泳和冷空气运动员的哮喘、气道炎症和上皮损伤
