title: Prophylactic and therapeutic treatment with the flavonone sakuranetin ameliorates LPS-induced acute lung injury.
abstract: Sakuranetin is the main isolate flavonoid fromBaccharis retusa(Asteraceae) leaves and exhibits anti-inflammatory and antioxidative activities. Acute respiratory distress syndrome is an acute failure of the respiratory system for which effective treatment is urgently necessary. This study investigated the preventive and therapeutic effects of sakuranetin on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice. Animals were treated with intranasal sakuranetin 30 min before or 6 h after instillation of LPS. Twenty-four hours after ALI was induced, lung function, inflammation, macrophages population markers, collagen fiber deposition, the extent of oxidative stress, and the expression of matrix metalloprotease-9 (MMP-9), tissue inhibitor of MMP-9 (TIMP-1) and NF-κB were evaluated. The animals began to show lung alterations 6 h after LPS instillation, and these changes persisted until 24 h after LPS administration. Preventive and therapeutic treatment with sakuranetin reduced the neutrophils in the peripheral blood and in the bronchial alveolar lavage. Sakuranetin treatment also reduced macrophage populations, particularly that of M1-like macrophages. In addition, sakurnaetin treatment reduced keratinocyte-derived chemokines (IL-8 homolog) and NF-κB levels, collagen fiber formation, MMM-9 and TIMP-1-positive cells, and oxidative stress in lung tissues compared with LPS animals treated with vehicle. Finally, sakuranetin treatment also reduced total protein, and the levels of TNF-α and IL-1β in the lung. This study shows that sakuranetin prevented and reduced pulmonary inflammation induced by LPS. Because sakuranetin modulates oxidative stress, the NF-κB pathway, and lung function, it may constitute a novel therapeutic candidate to prevent and treat ALI.
authors.affiliation: Biological Science Department, Federal University of São Paulo, Diadema, Brazil.
authors.forename: Márcia Isabel
authors.initials: MI
authors.lastname: Bittencourt-Mernak
authors.affiliation: Medicine Department, School of Medicine, University of São Paulo, São Paulo, Brazil.
authors.forename: Nathalia M
authors.initials: NM
authors.lastname: Pinheiro
authors.affiliation: Biological Science Department, Federal University of São Paulo, Diadema, Brazil.
authors.forename: Fernanda P R
authors.initials: FP
authors.lastname: Santana
authors.affiliation: Biological Science Department, Federal University of São Paulo, Diadema, Brazil.
authors.forename: Marina P
authors.initials: MP
authors.lastname: Guerreiro
authors.affiliation: Medicine Department, School of Medicine, University of São Paulo, São Paulo, Brazil.|University City of São Paulo (UNICID), São Paulo, Brazil.|Institute of Medical Assistance to the State Public Servant of São Paulo (IAMSPE), São Paulo, Brazil.
authors.forename: Beatriz M
authors.initials: BM
authors.lastname: Saraiva-Romanholo
authors.affiliation: Earth and Exact Science, Federal University of Brazil, São Paulo, Brazil.
authors.forename: Simone S
authors.initials: SS
authors.lastname: Grecco
authors.affiliation: Biological Science Department, Federal University of São Paulo, Diadema, Brazil.
authors.forename: Luciana C
authors.initials: LC
authors.lastname: Caperuto
authors.affiliation: Department of Medicine, Nephrology Division, Federal University of São Paulo, São Paulo, Brazil.
authors.forename: Raphael J F
authors.initials: RJ
authors.lastname: Felizardo
authors.affiliation: Medicine Department, School of Medicine, University of São Paulo, São Paulo, Brazil.|Department of Medicine, Nephrology Division, Federal University of São Paulo, São Paulo, Brazil.|Immunology Department, Biological Science Institute, University of São Paulo, São Paulo, Brazil; and.
authors.forename: Niels O S
authors.initials: NO
authors.lastname: Câmara
authors.affiliation: Medicine Department, School of Medicine, University of São Paulo, São Paulo, Brazil.
authors.forename: Iolanda F L C
authors.initials: IF
authors.lastname: Tibério
authors.affiliation: Medicine Department, School of Medicine, University of São Paulo, São Paulo, Brazil.
authors.forename: Mílton A
authors.initials: MA
authors.lastname: Martins
authors.affiliation: Earth and Exact Science, Federal University of Brazil, São Paulo, Brazil.
authors.forename: João Henrique G
authors.initials: JH
authors.lastname: Lago
authors.affiliation: Biological Science Department, Federal University of São Paulo, Diadema, Brazil; carla.prado@unifesp.br.|Medicine Department, School of Medicine, University of São Paulo, São Paulo, Brazil.|Bioscience Department, Federal University of São Paulo, Santos, Brazil.
authors.forename: Carla M
authors.initials: CM
authors.lastname: Prado
mesh_terms: D055371:Acute Lung Injury / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000517:prevention & control*; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D016764:Cell Polarity / Q000187:drug effects; D003094:Collagen / Q000378:metabolism; D003187:Compliance / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism; D005419:Flavonoids / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D018836:Inflammation Mediators / Q000378:metabolism; D007962:Leukocytes / Q000187:drug effects; D008070:Lipopolysaccharides; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008807:Mice, Inbred BALB C; D008954:Models, Biological; D018384:Oxidative Stress / Q000187:drug effects; D010766:Phosphorylation / Q000187:drug effects; D011014:Pneumonia / Q000097:blood / Q000150:complications / Q000188:drug therapy / Q000503:physiopathology; D021122:Protein Subunits / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism; D051996:Transcription Factor RelA / Q000378:metabolism; D000094162:Phytoalexins
chemical_list: D015415:Biomarkers; D003094:Collagen; D016207:Cytokines; D005419:Flavonoids; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D020780:Matrix Metalloproteinase 9; D021122:Protein Subunits; D012333:RNA, Messenger; D019715:Tissue Inhibitor of Metalloproteinase-1; D051996:Transcription Factor RelA; C099724:sakuranetin; D000094162:Phytoalexins
keywords: LPS; acute lung injury; inflammation; sakuranetin