Protective effect of zerumbone reduces lipopolysaccharide-induced acute lung injury via antioxidative enzymes and Nrf2/HO-1 pathway.
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.
Department of Emergency Medicine, Jen-Ai Hospital, Taichung, Taiwan.
Wai-Shing
WS
Leung
Department of Anatomy, School of Medicine, Chung Shan Medical University, Taichung, Taiwan.
Ming-Ling
ML
Yang
School of Public Health, Chung Shan Medical University, Taichung, Taiwan.
Shiuan-Shinn
SS
Lee
Department of Pharmacology, Jen-Ai Hospital, Taichung, Taiwan; Central Taiwan University of Science and Technology, Taichung, Taiwan.
Chi-Wen
CW
Kuo
School of Medical Applied Chemistry, Chung Shan Medical University, Taichung, Taiwan.
Yung-Chyuan
YC
Ho
School of Nutrition, , Chung Shan Medical University, Taichung, Taiwan.
Rosa
R
Huang-Liu
Department of Optometry, Asia University, Taichung, Taiwan; Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, Taiwan.
Hui-Wen
HW
Lin
Department of Pharmacology, School of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan; Department of Pharmacy, Chung Shan Medical University Hospital, Taichung 40201, Taiwan. Electronic address: kuanyh@csmu.edu.tw.
Yu-Hsiang
YH
Kuan
D055371:Acute Lung Injury / Q000188:drug therapy* / Q000276:immunology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D000975:Antioxidants / Q000627:therapeutic use*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D051547:Heme Oxygenase-1 / Q000378:metabolism*; D006801:Humans; D008070:Lipopolysaccharides / Q000276:immunology; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008813:Mice, Inbred ICR; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D009195:Peroxidase / Q000378:metabolism; D012717:Sesquiterpenes / Q000627:therapeutic use*; D015398:Signal Transduction / Q000187:drug effects; D030521:Zingiberaceae / Q000276:immunology
D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D008070:Lipopolysaccharides; D008565:Membrane Proteins; D051267:NF-E2-Related Factor 2; C495636:Nfe2l2 protein, mouse; D012717:Sesquiterpenes; C403304:zerumbone; D009195:Peroxidase; D051547:Heme Oxygenase-1; C496542:Hmox1 protein, mouse; D020780:Matrix Metalloproteinase 9
Acute lung injury; Antioxidative enzymes; HO-1; LPS; Nrf2; Zerumbone