title: Pretreatment with the compound asperuloside decreases acute lung injury via inhibiting MAPK and NF-κB signaling in a murine model.
abstract: Asperuloside, an iridoid glycoside found in Herba Paederiae, is a component from traditional Chinese herbal medicine. In this study, we aimed to investigate the protective effects and potential mechanisms of asperuloside action on inflammatory responses in lipopolysaccharide (LPS)-stimulated Raw 264.7 cells and an LPS-induced lung injury model. The pro-inflammatory cytokines and signaling pathways were measured by enzyme-linked immunosorbent assays (ELISA) and Western blotting to determine the effects of asperuloside. We found that asperuloside can significantly downregulate tumor necrosis factor alpha (TNF-α), interleukin (IL)-1β, and IL-6 levels in vitro and in vivo, and treatment with asperuloside significantly reduced the lung wet-to-dry weight, histological alterations and myeloperoxidase activity in a murine model of LPS-induced acute lung injury (ALI). In addition, Western blot analysis that pretreatment with asperuloside remarkably blunted the phosphorylation of inhibitor of nuclear factor kappa-B (IκBα), extracellular signal-related kinases 1 and 2 (ERK1/2), c-Jun. N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (p38MAPK) in LPS-stimulated inflammation. These results indicate that asperuloside exerts its anti-inflammatory effect in correlation with inhibition of a pro-inflammatory mediator through suppressing nuclear factor kappa-B (NF-κB) nuclear translocation and MAPK phosphorylation in a dose-dependent manner.
authors.affiliation: Key Laboratory of Zoonosis, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun, Jilin 130062, People's Republic of China.
authors.forename: Jiaming
authors.initials: J
authors.lastname: Qiu
authors.affiliation: Department of Outpatient Clinic, The Affiliated Hospital of Inner Monglia University for the Nationalities, Tongliao 028000, People's Republic of China.
authors.forename: Gefu
authors.initials: G
authors.lastname: Chi
authors.affiliation: Key Laboratory of Zoonosis, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun, Jilin 130062, People's Republic of China.
authors.forename: Qianchao
authors.initials: Q
authors.lastname: Wu
authors.affiliation: Hospital of He Ping Campus, Jilin University, Changchun, Jilin 130062, People's Republic of China.
authors.forename: Yanlei
authors.initials: Y
authors.lastname: Ren
authors.affiliation: Laboratory Animal Center, Jilin University, Changchun, Jilin 130062, People's Republic of China. Electronic address: cczjd@sina.com.
authors.forename: Chengzhen
authors.initials: C
authors.lastname: Chen
authors.affiliation: Key Laboratory of Zoonosis, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun, Jilin 130062, People's Republic of China. Electronic address: fhh70@163.com.
authors.forename: Haihua
authors.initials: H
authors.lastname: Feng
mesh_terms: D055371:Acute Lung Injury / Q000188:drug therapy*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D002460:Cell Line; D000081004:Cyclopentane Monoterpenes; D004195:Disease Models, Animal; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage*; D005960:Glucosides / Q000008:administration & dosage*; D006801:Humans; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000276:immunology; D008264:Macrophages / Q000187:drug effects* / Q000502:physiology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000378:metabolism*; D009195:Peroxidase / Q000378:metabolism; D011714:Pyrans / Q000008:administration & dosage*; D015398:Signal Transduction / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D000893:Anti-Inflammatory Agents; D000081004:Cyclopentane Monoterpenes; D004365:Drugs, Chinese Herbal; D005960:Glucosides; D053583:Interleukin-1beta; D015850:Interleukin-6; D008070:Lipopolysaccharides; D016328:NF-kappa B; D011714:Pyrans; D014409:Tumor Necrosis Factor-alpha; D009195:Peroxidase; D048051:p38 Mitogen-Activated Protein Kinases; C077956:asperuloside
keywords: Acute lung injury; Asperuloside; Cytokines; Lipopolysaccharide; MAPKs; NF-κB