Sclareol ameliorate lipopolysaccharide-induced acute lung injury through inhibition of MAPK and induction of HO-1 signaling
Autor: | Yung-Hung Hsieh, Hsin-Pao Pan, Jung-Chun Liao, Jeng-Shyan Deng, Shyh-Shyun Huang, Guan-Jhong Huang |
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Rok vydání: | 2017 |
Předmět: |
Lipopolysaccharides
Male 0301 basic medicine Lipopolysaccharide Acute Lung Injury Immunology Anti-Inflammatory Agents Nitric Oxide Synthase Type II Pharmacology Lung injury Nitric Oxide Nitric oxide Mice 03 medical and health sciences chemistry.chemical_compound Animals Immunology and Allergy Medicine Lung Cells Cultured Mice Inbred ICR biology medicine.diagnostic_test business.industry Sclareol respiratory system respiratory tract diseases Nitric oxide synthase IκBα 030104 developmental biology Bronchoalveolar lavage chemistry biology.protein Cytokines Tumor necrosis factor alpha Diterpenes Inflammation Mediators Mitogen-Activated Protein Kinases business Heme Oxygenase-1 Signal Transduction |
Zdroj: | International Immunopharmacology. 44:16-25 |
ISSN: | 1567-5769 |
DOI: | 10.1016/j.intimp.2016.12.026 |
Popis: | Sclareol is a natural fragrance compound that is used widely in the cosmetic and food industries. This study examined the effect of sclareol on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice. Mice were treated with sclareol 1 h before an intratracheal (I.T.) LPS challenge to induce an ALI model. The effects on lung tissue and lung injury were evaluated 6 h after LPS induction. Pretreatment with sclareol noticeably improved the LPS-induced histological alterations and edema in lung tissue. Sclareol also inhibited the release of pro-inflammatory mediators. Differences in nitric oxide (NO), tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1β), IL-6, and IL-10 were found in the bronchoalveolar lavage fluid (BALF) 6 h after LPS-induced lung injury. This study also found a reduced number of total cells and reduced protein concentrations in the BALF. There were also changes in the pulmonary wet/dry (W/D) weight ratio, antioxidant enzyme activity, and myeloperoxidase activity in lung tissues. Sclareol effectively blocked the phosphorylation of mitogen-activated protein kinases (MAPKs) and impeded the protein expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). The compound boosted the expression of heme oxygenase-1 (HO-1) and inhibited the breakdown of nuclear factor-kappa B (NF-κB) and inhibitor of kappa B (IκBα). To the best of the authors' knowledge, this study is the first to demonstrate that sclareol effectively inhibits acute lung edema, and the results suggest that sclareol may be a potential agent for the treatment of ALI. The potential therapeutic benefits may include the attenuation of LPS-induced pulmonary inflammation due to sclareol's effects on several pathways, including NF-κB, MAPKs and HO-1, as well as the regulation of antioxidant enzyme activity. |
Databáze: | OpenAIRE |
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