title: Sclareol ameliorate lipopolysaccharide-induced acute lung injury through inhibition of MAPK and induction of HO-1 signaling.
abstract: 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 1h before an intratracheal (I.T.) LPS challenge to induce an ALI model. The effects on lung tissue and lung injury were evaluated 6h 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) 6h 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.
authors.affiliation: Department of Chinese Pharmaceutical Sciences and Chinese Medicine Resources, China Medical University, Taichung, Taiwan; Department of Pharmacy, Taichung Armed Forces General Hospital, Taichung, Taiwan; National Defense Medical Center, Taipei, Taiwan; Taichung County Pharmacist Association, Taiwan.
authors.forename: Yung-Hung
authors.initials: YH
authors.lastname: Hsieh
authors.affiliation: Department of Health and Nutrition Biotechnology, Asia University, Taichung, Taiwan.
authors.forename: Jeng-Shyan
authors.initials: JS
authors.lastname: Deng
authors.affiliation: Department of Pharmacy, Taichung Armed Forces General Hospital, Taichung, Taiwan; National Defense Medical Center, Taipei, Taiwan.
authors.forename: Hsin-Pao
authors.initials: HP
authors.lastname: Pan
authors.affiliation: School of Pharmacy, College of Pharmacy, China Medical University, Taichung, Taiwan.
authors.forename: Jung-Chun
authors.initials: JC
authors.lastname: Liao
authors.affiliation: School of Pharmacy, College of Pharmacy, China Medical University, Taichung, Taiwan. Electronic address: sshuang@mail.cmu.edu.tw.
authors.forename: Shyh-Shyun
authors.initials: SS
authors.lastname: Huang
authors.affiliation: Department of Chinese Pharmaceutical Sciences and Chinese Medicine Resources, China Medical University, Taichung, Taiwan. Electronic address: gjhuang@mail.cmu.edu.tw.
authors.forename: Guan-Jhong
authors.initials: GJ
authors.lastname: Huang
mesh_terms: D055371:Acute Lung Injury / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D004224:Diterpenes / Q000627:therapeutic use*; D051547:Heme Oxygenase-1 / Q000378:metabolism*; D018836:Inflammation Mediators / Q000378:metabolism; D008070:Lipopolysaccharides / Q000276:immunology; D008168:Lung / Q000187:drug effects* / Q000473:pathology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D004224:Diterpenes; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D009569:Nitric Oxide; C070760:sclareol; D052247:Nitric Oxide Synthase Type II; D051547:Heme Oxygenase-1; D020928:Mitogen-Activated Protein Kinases
keywords: Acute lung injury; Anti-inflammation; HO-1; Sclareol