title: Isorhamnetin protects mice from lipopolysaccharide-induced acute lung injury via the inhibition of inflammatory responses.
abstract: OBJECTIVE
  Isorhamnetin (Isor), a 3-O-methylated metabolite of quercetin, has shown antioxidant and anti-proliferative effects in previous studies. In this study, we investigated the anti-inflammatory effect of Isor on LPS-induced acute lung injury (ALI). Accordingly, we evaluated the effect of Isor on cytokine production elevated by LPS (1 μg/ml) in vitro. An in vivo ALI murine model was also established via lipopolysaccharide inhalation (LPS, 20 mg/kg), and the cytokine levels and inflammatory cell count in bronchoalveolar lavage fluid (BALF) were evaluated. The observed lung injury was assessed using histopathologic sections via H&E straining. Furthermore, to investigate whether the anti-inflammatory effect of Isor is associated with NF-κB and MAPKs pathway activation, the phosphorylated levels of ERK, JNK, IκBa and NF-κB(p65) were determined.
  
  
  RESULTS
  Isor significantly inhibited LPS-induced TNF-α, IL-1β and IL-6 secretion both in vitro and in vivo. Neutrophil infiltration and edema in an ALI model were substantially alleviated. The histopathological changes induced by LPS were lessened by Isor. Additionally, Isor notably suppressed the phosphorylation of ERK, JNK, IκBa and NF-κB(p65) activated by LPS in vivo.
  
  
  CONCLUSIONS
  Isor showed efficient protective effects on an LPS-induced ALI model. MAPKs and NF-κB pathways are critical for Isor to perform its protective effects.
authors.affiliation: Institute of Frontier Medical Science, Jilin University, Changchun, 130021, People's Republic of China.|Department of Outpatient Clinic, The Affiliated Hospital of Inner Mongolia University for the Nationalities, Tongliao, 028000, People's Republic of China.
authors.forename: Gefu
authors.initials: G
authors.lastname: Chi
authors.affiliation: College of Veterinary Medicine, Jilin University, Changchun, 130062, People's Republic of China.
authors.forename: Weiting
authors.initials: W
authors.lastname: Zhong
authors.affiliation: College of Veterinary Medicine, Jilin University, Changchun, 130062, People's Republic of China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: College of Veterinary Medicine, Jilin University, Changchun, 130062, People's Republic of China.
authors.forename: Gejin
authors.initials: G
authors.lastname: Lu
authors.affiliation: College of Veterinary Medicine, Jilin University, Changchun, 130062, People's Republic of China.
authors.forename: Hongming
authors.initials: H
authors.lastname: Lü
authors.affiliation: College of Veterinary Medicine, Jilin University, Changchun, 130062, People's Republic of China. wdc9928@yahoo.com.cn.
authors.forename: Dacheng
authors.initials: D
authors.lastname: Wang
authors.affiliation: Institute of Frontier Medical Science, Jilin University, Changchun, 130021, People's Republic of China. sunfei_1234@126.com.
authors.forename: Fei
authors.initials: F
authors.lastname: Sun
mesh_terms: D055371:Acute Lung Injury / Q000139:chemically induced* / Q000473:pathology / Q000517:prevention & control*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D016207:Cytokines / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D008168:Lung / Q000473:pathology; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D020556:Neutrophil Infiltration / Q000187:drug effects; D011654:Pulmonary Edema / Q000139:chemically induced / Q000473:pathology; D011794:Quercetin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000067996:RAW 264.7 Cells
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D008070:Lipopolysaccharides; D016328:NF-kappa B; C047368:3-methylquercetin; D011794:Quercetin; D020928:Mitogen-Activated Protein Kinases
keywords: ALI; Isorhamnetin; LPS; MAPKs; NF-κB(p65)