title: Daidzein attenuates lipopolysaccharide-induced acute lung injury via toll-like receptor 4/NF-kappaB pathway.
abstract: Daidzein, a diphenolic isoflavone from many plants and herbs, has been reported to have anti-inflammatory properties. However, the effects of daidzein on lipopolysaccharide (LPS)-induced acute lung injury have not been determined. The aim of this study was to detect the effects of daidzein on LPS-induced acute lung injury and investigate the molecular mechanisms. Daidzein was intraperitoneally injected (2, 4, 8 mg/kg) 30 min after intratracheal instillation of LPS (5 mg/kg) in rats. The results showed that daidzein treatment remarkably improved the pulmonary histology and decreased the lung wet/dry weight ratios. We also found that daidzein significantly inhibited LPS-induced increases of macrophages and neutrophils infiltration of lung tissues, as well as markedly attenuated MPO activity. Moreover, daidzein effectively reduced the inflammatory cytokines release and total protein in bronchoalveolar lavage fluids (BALF). Furthermore, daidzein significantly inhibited LPS-induced toll-like receptor 4 (TLR4) and myeloid differentiation factor 88 (MyD88) protein up-expressions and NF-κB activation in lung tissues. In vitro, daidzein obviously inhibited the expressions of TLR4 and MyD88 and the activation of NF-κB in LPS-stimulated A549 alveolar epithelial cells. In conclusion, these data indicate that the anti-inflammatory effects of daidzein against LPS-induced ALI may be due to its ability to inhibit TLR4-MyD88-NF-κB pathway and daidzein may be a potential therapeutic agent for LPS-induced ALI.
authors.affiliation: Department of Anesthesiology, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, PR China; Department of Anesthesiology, The Affiliated Hospital of Xuzhou Medical College, Xuzhou 221002, PR China.
authors.forename: Guang
authors.initials: G
authors.lastname: Feng
authors.affiliation: Department of Anesthesiology, The Second Affiliated Hospital of Soochow University, Suzhou 215004, PR China.
authors.forename: Bo
authors.initials: B
authors.lastname: Sun
authors.affiliation: Department of Anesthesiology, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, PR China; Department of Anesthesiology, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, PR China. Electronic address: grahamjessie@126.com.
authors.forename: Tian-zuo
authors.initials: TZ
authors.lastname: Li
mesh_terms: D055371:Acute Lung Injury / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000009:adverse effects; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D007529:Isoflavones / Q000008:administration & dosage* / Q000009:adverse effects; D008070:Lipopolysaccharides / Q000276:immunology; D008168:Lung / Q000187:drug effects* / Q000473:pathology; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology; D008297:Male; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D009504:Neutrophils / Q000187:drug effects* / Q000276:immunology; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D051197:Toll-Like Receptor 4 / Q000378:metabolism*
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D018836:Inflammation Mediators; D007529:Isoflavones; D008070:Lipopolysaccharides; D016328:NF-kappa B; D051197:Toll-Like Receptor 4; C004742:daidzein; D009195:Peroxidase
keywords: Acute lung injury; Acute respiratory distress syndrome; Daidzein; Lipopolysaccharide; NF-kappaB; Toll-like receptor 4