Inhibitory effects of flavonoids extracted from licorice on lipopolysaccharide-induced acute pulmonary inflammation in mice
Inhibitory effects of flavonoids extracted from licorice on lipopolysaccharide-induced acute pulmonary inflammation in mice
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甘草黄酮对脂多糖诱导的小鼠急性肺部炎症的抑制作用
DOI：
10.1016/j.intimp.2008.11.004
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发表时间：
2009-02-01
影响因子：
5.6
通讯作者：
Xie, Qiang-Min
中科院分区：
文献类型：
--
作者：
Me, Yi-Cheng;Dong, Xin-Wei;Xie, Qiang-Min
呼吸道炎症在急性呼吸窘迫综合征(ARDS)、哮喘和慢性阻塞性肺疾病(COPD)的发病机制中起着重要作用，抗炎治疗有效地改善了这些疾病的症状。为了开发潜在的治疗肺部炎症的化合物，我们研究了从甘草根中提取的甘草黄酮类化合物(LF)对内毒素(LPS)诱导的小鼠急性肺炎症的影响。肺泡灌洗液(BALF)中中性粒细胞、巨噬细胞和淋巴细胞聚集明显减少，其中以抑制中性粒细胞浸润为主，30 mg/kg剂量的作用与1 mg/kg的地塞米松作用相当。与其对中性粒细胞浸润的影响相一致，LF处理可显著提高包括内毒素在内的BALF超氧化物歧化酶活性，并显著降低肺组织髓过氧化物酶活性。此外，LF30 mg/kg可显著降低LPS诱导的肺组织中IL-1β和IL-1βmRNA的表达。不同剂量的LF不仅能显著降低肺水含量的升高，而且能明显减轻内毒素诱导的肺组织学改变。因此，我们认为LF通过抑制炎症细胞的浸润和炎性介质的释放，从而减少中性粒细胞向肺内的募集和中性粒细胞介导的氧化损伤，从而有效地减轻了内毒素所致的肺部炎症，为从甘草黄酮类提取物中开发抗炎化合物提供了潜在的理论基础。(C)2008爱思唯尔B.V.保留所有权利。
Airway inflammation plays important roles in the pathogenesis of acute respiratory distress syndrome (ARDS), asthma and chronic obstructive pulmonary disease (COPD), and anti-inflammatory treatment effectively improves the symptoms of these diseases. To develop the potentially therapeutic compounds for the treatment of pulmonary inflammation, we investigated the effects of licorice flavonoids (LF) extracted from the roots of Glycyrrhiza uralensis (licorice) on lipopolysaccharide (LPS)-induced acute pulmonary inflammation in mice. Acute pulmonary inflammation was induced by intracheal instillation with LPS, treatment with LF at dosages of 3, 10 and 30 mg/kg significantly reduced the LPS-induced inflammatory cells, including neutrophils, macrophages and lymphocytes accumulation in bronchoalveolar lavage fluids (BALF), among these inflammatory cells, LF predominately inhibited neutrophil infiltration, and the maximal effect (30 mg/kg) was as comparable as dexamethasone treatment at I mg/kg. Consistent with its effects on neutrophil infiltration, LF treatment significantly increased LPS-incluced BALF superoxide dismutase activity, and significantly decreased lung myeloperoxidase activity as well. Furthermore, treatment with LF at 30 mg/ kg significantly reduced LPS-induced lung TNF alpha and IL-1 beta mRNA expression at 6 h and 24 h after LPS instillation, respectively. Finally, LF at different dosages not only significantly decreased the elevation of lung water content but also markedly attenuated LPS-induced histological alteration. Therefore, we suggest that LF effectively attenuates LPS-incluced pulmonary inflammation through inhibition of inflammatory cells infiltration and inflammatory mediator release which subsequently reduces neutrophil recruitment into lung and neutrophil-mediated oxidative injury, and this study provides with the potential rationale for development of anti-inflammatory compounds from flavonoid extracts of licorice. (C) 2008 Elsevier B.V. All rights reserved.