Leung Wai-Shing, Yang Ming-Ling, Lee Shiuan-Shinn, Kuo Chi-Wen, Ho Yung-Chyuan, Huang-Liu Rosa, Lin Hui-Wen, Kuan Yu-Hsiang
Department of Emergency Medicine, Jen-Ai Hospital, Taichung, Taiwan.
Department of Anatomy, School of Medicine, Chung Shan Medical University, Taichung, Taiwan.
Int Immunopharmacol. 2017 May;46:194-200. doi: 10.1016/j.intimp.2017.03.008.
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.
急性肺损伤（ALI）是一种发病率和死亡率都很高的严重疾病。尽管有治疗ALI的有效策略，但尚未建立一种被广泛接受的特异性药物疗法。姜黄烯是莪术（Zingiber zerumbet Smith）的主要活性植物化学成分，具有多种有益的生物学和药理活性，如抗氧化、抗炎、免疫调节和抗癌作用。我们旨在研究姜黄烯在脂多糖（LPS）诱导的ALI小鼠模型中的潜在保护作用及其机制。姜黄烯预处理可抑制LPS诱导的ALI小鼠肺组织中的组织病理学变化，如中性粒细胞浸润、肺泡屏障厚度增加、出血和透明膜形成。此外，姜黄烯不仅抑制了LPS诱导的髓过氧化物酶（MPO）和金属蛋白酶-9（MMP-9）的激活，还抑制了肺组织中的脂质过氧化。而且，姜黄烯预处理可逆转LPS降低的抗氧化酶活性，包括超氧化物歧化酶、过氧化氢酶和谷胱甘肽过氧化物酶，并增强LPS诱导的核因子红细胞2相关因子（Nrf2）和血红素加氧酶（HO-1）的表达。本研究的这些结果表明，姜黄烯对LPS诱导的ALI的保护机制是通过上调抗氧化酶和Nrf2/HO-1途径实现的。
