title: The protective effect of CDDO-Me on lipopolysaccharide-induced acute lung injury in mice.
abstract: CDDO-Me, initiated in a phase II clinical trial, is a potential useful therapeutic agent for cancer and inflammatory dysfunctions, whereas the therapeutic efficacy of CDDO-Me on LPS-induced acute lung injury (ALI) has not been reported as yet. The purpose of the present study was to explore the protective effect of CDDO-Me on LPS-induced ALI in mice and to investigate its possible mechanism. BalB/c mice received CDDO-Me (0.5mg/kg, 2mg/kg) or dexamethasone (5mg/kg) intraperitoneally 1h before LPS stimulation and were sacrificed 6h later. W/D ratio, lung MPO activity, number of total cells and neutrophils, pulmonary histopathology, IL-6, IL-1β, and TNF-α in the BALF were assessed. Furthermore, we estimated iNOS, IL-6, IL-1β, and TNF-α mRNA expression and NO production as well as the activation of the three main MAPKs, AkT, IκB-α and p65. Pretreatment with CDDO-Me significantly ameliorated W/D ratio, lung MPO activity, inflammatory cell infiltration, and inflammatory cytokine production in BALF from the in vivo study. Additionally, CDDO-Me had beneficial effects on the intervention for pathogenesis process at molecular, protein and transcriptional levels in vitro. These analytical results provided evidence that CDDO-Me could be a potential therapeutic candidate for treating LPS-induced ALI.
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, No. 24 Tongjiaxiang, Nanjing 210009, Jiangsu, China.
authors.forename: Tong
authors.initials: T
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, No. 24 Tongjiaxiang, Nanjing 210009, Jiangsu, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Mou
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, No. 24 Tongjiaxiang, Nanjing 210009, Jiangsu, China.
authors.forename: Jiani
authors.initials: J
authors.lastname: Tan
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, No. 24 Tongjiaxiang, Nanjing 210009, Jiangsu, China.
authors.forename: Linlin
authors.initials: L
authors.lastname: Wei
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, No. 24 Tongjiaxiang, Nanjing 210009, Jiangsu, China.
authors.forename: Yixue
authors.initials: Y
authors.lastname: Qiao
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, No. 24 Tongjiaxiang, Nanjing 210009, Jiangsu, China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Wei
authors.affiliation: School of Pharmacy, China Pharmaceutical University, No.24 Tongjiaxiang, Nanjing 210009, Jiangsu, China.
authors.forename: Pengjun
authors.initials: P
authors.lastname: Xiang
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, No. 24 Tongjiaxiang, Nanjing 210009, Jiangsu, China.
authors.forename: Sixun
authors.initials: S
authors.lastname: Peng
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, No. 24 Tongjiaxiang, Nanjing 210009, Jiangsu, China.
authors.forename: Yihua
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, No. 24 Tongjiaxiang, Nanjing 210009, Jiangsu, China. Electronic address: cpudahuang@163.com.
authors.forename: Zhangjian
authors.initials: Z
authors.lastname: Huang
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, No. 24 Tongjiaxiang, Nanjing 210009, Jiangsu, China. Electronic address: huijicpu@163.com.
authors.forename: Hui
authors.initials: H
authors.lastname: Ji
mesh_terms: D055371:Acute Lung Injury / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology; D000818:Animals; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D008070:Lipopolysaccharides / Q000276:immunology; D008168:Lung / Q000187:drug effects* / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009504:Neutrophils / Q000187:drug effects* / Q000276:immunology; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D009828:Oleanolic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives*; D009195:Peroxidase / Q000378:metabolism
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D009828:Oleanolic Acid; C445068:bardoxolone methyl; D009195:Peroxidase; D052247:Nitric Oxide Synthase Type II; D048049:Extracellular Signal-Regulated MAP Kinases
keywords: ALI; CDDO-Me; LPS; RAW 264.7 cells