title: Magnolol ameliorates lipopolysaccharide-induced acute lung injury in rats through PPAR-γ-dependent inhibition of NF-kB activation.
abstract: Acute lung injury (ALI) has a high morbidity and mortality rate due to the serious inflammation and edema occurred in lung. Magnolol extracted from Magnolia officinalis, has been reported to exhibit anti-inflammatory, and antioxidant activities. Peroxisome proliferator-activated receptors (PPARs) are known to exert a cytoprotective effect against cellular inflammatory stress and oxidative injury. The aim of this study was to explore the involvement of PPAR-γ in the beneficial effect of magnolol in lipopolysaccharide (LPS)-induced ALI. We found that treatment with magnolol greatly improved the pathological features of ALI evidenced by reduction of lung edema, polymorphonuclear neutrophil infiltration, ROS production, the levels of pro-inflammatory cytokines in bronchoalveolar lavage fluid (BALF), the expression of iNOS and COX-2, and NF-κB activation in lungs exposed to LPS. Importantly, magnolol is capable of increasing the PPAR-γ expression and activity in lungs of ALI. However, blocking PPAR-γ activity with GW9662 markedly abolished the protective and anti-inflammatory effects of magnolol. Taken together, the present study provides a novel mechanism accounting for the protective effect of magnolol in LPS-induced ALI is at least partly attributed to induction of PPAR-γ in lungs, and in turn suppressing NF-κB-related inflammatory responses.
authors.affiliation: Division of Nuclear Medicine, Taipei City Hospital Zhongxiao Branch, Taipei, Taiwan; Department of Biomedical Imaging and Radiological Sciences, Program in Molecular Medicine, National Yang-Ming University and Academia Sinica, Taipei, Taiwan.
authors.forename: Ming-Hsien
authors.initials: MH
authors.lastname: Lin
authors.affiliation: Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Meng-Chuan
authors.initials: MC
authors.lastname: Chen
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan.
authors.forename: Tso-Hsiao
authors.initials: TH
authors.lastname: Chen
authors.affiliation: School of Post-Baccalaureate Chinese Medicine, Tzu Chi University, Hualien, Taiwan.
authors.forename: Heng-Yuan
authors.initials: HY
authors.lastname: Chang
authors.affiliation: Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan; Institute of Medical Sciences, Tzu Chi University, Hualien, Taiwan; Department of Biotechnology, Asia University, Taichung, Taiwan; China Medical University Hospital, China Medical University, Taichung, Taiwan. Electronic address: tcchou48@mail.tcu.edu.tw.
authors.forename: Tz-Chong
authors.initials: TC
authors.lastname: Chou
mesh_terms: D055371:Acute Lung Injury / Q000139:chemically induced* / Q000473:pathology / Q000517:prevention & control*; D000813:Anilides / Q000494:pharmacology; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D001713:Biphenyl Compounds / Q000037:antagonists & inhibitors / Q000627:therapeutic use*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D016207:Cytokines / Q000032:analysis / Q000378:metabolism; D017705:Lignans / Q000037:antagonists & inhibitors / Q000627:therapeutic use*; D008070:Lipopolysaccharides; D008297:Male; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D020556:Neutrophil Infiltration; D018384:Oxidative Stress / Q000187:drug effects; D047495:PPAR gamma / Q000037:antagonists & inhibitors*; D009195:Peroxidase / Q000378:metabolism; D011654:Pulmonary Edema / Q000473:pathology / Q000517:prevention & control; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: C457499:2-chloro-5-nitrobenzanilide; D000813:Anilides; D000894:Anti-Inflammatory Agents, Non-Steroidal; D001713:Biphenyl Compounds; D016207:Cytokines; D017705:Lignans; D008070:Lipopolysaccharides; D016328:NF-kappa B; D047495:PPAR gamma; D017382:Reactive Oxygen Species; C005498:magnolol; D009195:Peroxidase
keywords: Acute lung injury; Lipopolysaccharide; Magnolol; Peroxisome proliferator-activated receptor gamma