title: Protective effect of cryptotanshinone on lipopolysaccharide-induced acute lung injury in mice.
abstract: Crytotanshinone (CTN), one of the main constituents of tanshinones, has been reported to exhibit anti-tumor, anti-inflammatory and other important therapeutic activities. The aim of this study was to investigate the potential therapeutic effects of CTN on murine model of lipopolysaccharide (LPS)-induced acute lung injury (ALI). Male BALB/c mice were pretreated with dexamethasone or CTN 1h before intranasal instillation of LPS. Seven hours after LPS administration, the myeloperoxidase (MPO) in lung tissues, lung wet/dry weight ratio and inflammatory cells in the bronchoalveolar lavage fluid (BALF) were determined. The effects of CTN on pro-inflammatory cytokines and signaling pathways were analyzed by enzyme-linked immunosorbent assay (ELISA) and Western blot. The results showed that CTN significantly inhibited LPS induced increases of macrophages and neutrophils infiltration of lung tissues, as well as markedly attenuated MPO activity. Furthermore, CTN significantly reduced the wet/dry weight ratio of lungs and the concentrations of TNF-α, IL-6 and IL-1β in BALF. Compared with LPS group, lung histopathologic changes were less pronounced in the CTN pretreated mice. Additionally, western blotting showed that CTN efficiently inhibited the phosphorylation of IκB-α, p65 NF-κB and the expression of TLR4. Taken together, our results suggest that the anti-inflammatory effects of CTN against LPS-induced acute lung injury may be due to its ability to inhibit TLR4 mediated NF-κB signaling pathways. CTN may be a promising potential therapeutic reagent for ALI treatment.
authors.affiliation: Department of Respiratory Medicine, the First Hospital, Jilin University, Changchun, 130021, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Tang
authors.affiliation: Department of lung Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, 300060, China.
authors.forename: Yulong
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Emergency Medicine, the First Hospital, Jilin University, Changchun, 130021, China.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Chu
authors.affiliation: Department of Radiotherapy, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, 300060, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Yan
authors.affiliation: Department of Respiratory Medicine, the First Hospital, Jilin University, Changchun, 130021, China. Electronic address: lijunxufyh@163.com.
authors.forename: Lijun
authors.initials: L
authors.lastname: Xu
mesh_terms: D055371:Acute Lung Injury / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D002452:Cell Count; D016207:Cytokines / Q000276:immunology; D008070:Lipopolysaccharides; D008168:Lung / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000276:immunology; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology; D010616:Phenanthrenes / Q000494:pharmacology / Q000627:therapeutic use*; D020011:Protective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D051197:Toll-Like Receptor 4 / Q000276:immunology
chemical_list: D016207:Cytokines; D008070:Lipopolysaccharides; D016328:NF-kappa B; D010616:Phenanthrenes; D020011:Protective Agents; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; C037886:cryptotanshinone
keywords: Acute lung injury; Crytotanshinone; Lipopolysaccharide; Nuclear factor-kappaB; Toll-like receptor