title: Cepharanthine, an alkaloid from Stephania cepharantha Hayata, inhibits the inflammatory response in the RAW264.7 cell and mouse models.
abstract: The aim of this study was to investigate the protective effects of cepharanthine (CEP) on inflammation in lipopolysaccharide (LPS)-stimulated RAW264.7 cells in vitro and a LPS-induced lung injury model in vivo. RAW264.7 cells were treated with various concentrations of CEP for 1 h followed by incubation with or without 1 μg/ml LPS for 18 h. TNF-α, IL-6, and IL-1β in the supernatants were measured by ELISA. Nuclear factor-κB (NF-κB) and mitogen-activated protein kinase pathways were analyzed by Western blot. Mice were randomly divided into control group, LPS group, CEP + LPS group, and dexamethasone + LPS group. A male BALB/c mouse model of acute lung injury was induced by LPS. Bronchoalveolar lavage fluid was collected for inflammatory cell count and cytokine assays. Histopathologic examination was performed on mice that were not subjected to bronchoalveolar lavage fluid collection. CEP dose-dependently inhibited the release of TNF-α, IL-6, and IL-1β in LPS-stimulated RAW264.7 cells. Significantly, CEP dose-dependently suppressed NF-κB activation, IκBα degradation, and phosphorylation of ERK, JNK, and p38 induced by LPS. In vivo, it was also observed that CEP attenuated lung histopathologic changes and down-regulated the level of pro-inflammatory cytokines, including TNF-α, IL-1β, and IL-6, in the mouse acute lung injury model. These results suggest that CEP potentially decreases inflammation in vitro and in vivo and might be a therapeutic agent against inflammatory diseases.
authors.affiliation: College of Animal Science and Technology, Jilin Agricultural University, Changchun, 130062, People's Republic of China.
authors.forename: Hailong
authors.initials: H
authors.lastname: Huang
authors.forename: Guixue
authors.initials: G
authors.lastname: Hu
authors.forename: Chunfeng
authors.initials: C
authors.lastname: Wang
authors.forename: Hao
authors.initials: H
authors.lastname: Xu
authors.forename: Xiaoqing
authors.initials: X
authors.lastname: Chen
authors.forename: Aidong
authors.initials: A
authors.lastname: Qian
mesh_terms: D055371:Acute Lung Injury / Q000188:drug therapy*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D044182:Benzylisoquinolines / Q000494:pharmacology*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002460:Cell Line; D002470:Cell Survival; D003907:Dexamethasone / Q000494:pharmacology; D004195:Disease Models, Animal; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D020672:I-kappa B Proteins / Q000378:metabolism; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy* / Q000517:prevention & control; D053583:Interleukin-1beta / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008070:Lipopolysaccharides; D008264:Macrophages; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D000072000:NF-KappaB Inhibitor alpha; D010766:Phosphorylation; D028321:Plant Preparations; D031607:Stephania / Q000378:metabolism; D051996:Transcription Factor RelA / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism; D052117:Benzodioxoles
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D044182:Benzylisoquinolines; D003907:Dexamethasone; D048049:Extracellular Signal-Regulated MAP Kinases; D020672:I-kappa B Proteins; D053583:Interleukin-1beta; D015850:Interleukin-6; D048031:JNK Mitogen-Activated Protein Kinases; D008070:Lipopolysaccharides; D000072000:NF-KappaB Inhibitor alpha; D028321:Plant Preparations; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; D048051:p38 Mitogen-Activated Protein Kinases; C587672:IL1B protein, mouse; C000606205:Nfkbia protein, mouse; C006947:cepharanthine; D052117:Benzodioxoles
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