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Sclareol ameliorate lipopolysaccharide-induced acute lung injury through inhibition of MAPK and induction of HO-1 signaling
Institution:1. Department of Chinese Pharmaceutical Sciences and Chinese Medicine Resources, China Medical University, Taichung, Taiwan;2. Department of Pharmacy, Taichung Armed Forces General Hospital, Taichung, Taiwan;3. National Defense Medical Center, Taipei, Taiwan;4. Taichung County Pharmacist Association, Taiwan;5. Department of Health and Nutrition Biotechnology, Asia University, Taichung, Taiwan;6. School of Pharmacy, College of Pharmacy, China Medical University, Taichung, Taiwan;1. Department of ICU, The First Hospital of Jilin University, Changchun 130021, PR China;2. Department of the First Operating Room, The First Hospital of Jilin University, Changchun 130021, PR China;3. Department of Radiology, The First Hospital of Jilin University, Changchun 130021, PR China;4. Department of the Second Operating Room, The First Hospital of Jilin University, Changchun 130021, PR China;5. Department of Thoracic Surgery, The First Hospital of Jilin University, Changchun 130021, PR China;6. Department of Neonatology, The First Hospital of Jilin University, Changchun 130021, PR China;1. Department of Clinical Pharmacy, School of Pharmacy, Taipei Medical University, Taipei, Taiwan;2. Department of Pharmacy, Taipei Medical University-Wan Fang Medical Center, Taipei, Taiwan;3. Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan;4. Department of Statistics, University of Virginia, Charlottesville, Virginia, USA;1. Dept. of Pharmacology, School of Pharmacy, Ahvaz Jundishapur University of Medical Sciences (AJUMS), Ahvaz, Iran;2. Dept. of Pharmacology, School of Medicine, Physiology Research Center, Ahvaz Jundishapur University of Medical Sciences (AJUMS), Ahvaz, Iran;3. Dept. of Anatomical Sciences, School of Medicine, Ahvaz Jundishapur University of Medical Sciences (AJUMS), Ahvaz, Iran
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 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.
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