Protective effect of zerumbone reduces lipopolysaccharide-induced acute lung injury via antioxidative enzymes and Nrf2/HO-1 pathway
Protective effect of zerumbone reduces lipopolysaccharide-induced acute lung injury via antioxidative enzymes and Nrf2/HO-1 pathway
复制标题
DOI：
10.1016/j.intimp.2017.03.008
复制
发表时间：
2017-05-01
影响因子：
5.6
通讯作者：
Kuan, Yu-Hsiang
中科院分区：
文献类型：
--
作者：
Leung, Wai-Shing;Yang, Ming-Ling;Kuan, Yu-Hsiang
急性肺损伤(ALI)是一种发病率和死亡率都很高的严重疾病。虽然有治疗ALI的有效策略，但被广泛接受的特效药物疗法尚未建立。泽龙骨是生姜中的主要活性植物化学成分，具有抗氧化、抗炎、免疫调节、抗癌等多种有益的生物学和药理活性。本研究旨在探讨泽龙骨对脂多糖诱导的小鼠急性肺损伤的保护作用及其机制。泽伦骨预处理可抑制脂多糖诱导的小鼠肺组织中性粒细胞浸润、肺泡屏障增厚、出血、透明膜形成等组织病理学改变。此外，泽龙骨不仅能抑制脂多糖诱导的髓过氧化物酶(MPO)和金属肽酶-9(MMP9)的激活，而且还能抑制肺组织的脂质过氧化反应。此外，泽伦骨预处理可逆转脂多糖引起的超氧化物歧化酶、过氧化氢酶、谷胱甘肽过氧化物酶等抗氧化酶活性的降低，增强内毒素诱导的核因子红系2相关因子(Nrf2)和血红素加氧酶(HO-1)的表达。本研究结果提示，泽龙骨通过上调抗氧化酶和Nrf2/HO-1途径对内毒素诱导的ALI具有保护作用。(C)2017爱思唯尔B.V.保留所有权利。
Acute lung injury (ALI) is a serious disease with high morbidity and mortality rate. Although there are effective strategies for treatment of ALI; a widely accepted specific pharmacotherapy has not yet established. Zerumbone, the major active phytochemical compound from Zingiber zerumbet Smith, exhibits various beneficial biological and pharmacological activities, such as antioxidation, anti-inflammation, immunomodulation, and anti-cancer. We aimed to study the potential protective effects and mechanisms of zerumbone in mouse model of lipopolysaccharide (LPS)-induced ALI Pretreatment with zerumbone inhibited the histopatholgical changes such as neutrophils infiltration, increased in alveolar barrier thickness, hemorrhage, and hyaline membrane formation occurred in lungs in LPS-induced ALI. In addition, not only LPS-induced activation of myeloperoxidase (MPO) and metallopeptidase-9 (MMP-9) was suppressed by zerumbone, but also lipid peroxidation in lungs was inhibited as well. Moreover, pretreatment with zerumbone reversed the antioxidative enzymes activities, including superoxide dismutase, catalase, and glutathione peroxidase, decreased by LPS and enhanced the expression of nuclear factor erythroid 2-related factor (Nrf2) and heme oxygenase (HO-1) induced by LPS. These results from present study suggested that the protective mechanisms of zerumbone on LPS-induced ALI were via up regulation of antioxidative enzymes and Nrf2/HO-1 pathway. (C) 2017 Elsevier B.V. All rights reserved.