title: Isovitexin Exerts Anti-Inflammatory and Anti-Oxidant Activities on Lipopolysaccharide-Induced Acute Lung Injury by Inhibiting MAPK and NF-κB and Activating HO-1/Nrf2 Pathways.
abstract: Oxidative damage and inflammation are closely associated with the pathogenesis of acute lung injury (ALI). Thus, we explored the protective effect of isovitexin (IV), a glycosylflavonoid, in the context of ALI. To accomplish this, we created in vitro and in vivo models by respectively exposing macrophages to lipopolysaccharide (LPS) and using LPS to induce ALI in mice. In vitro, our results showed that IV treatment reduced LPS-induced pro-inflammatory cytokine secretion, iNOS and COX-2 expression and decreased the generation of ROS. Consistent findings were obtained in vivo. Additionally, IV inhibited H2O2-induced cytotoxicity and apoptosis. However, these effects were partially reversed following the use of an HO-1 inhibitor in vitro. Further studies revealed that IV significantly inhibited MAPK phosphorylation, reduced NF-κB nuclear translocation, and upregulated nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase 1 (HO-1) expression in RAW 264.7 cells. In vivo, pretreatment with IV attenuated histopathological changes, infiltration of polymorphonuclear granulocytes and endothelial activation, decreased the expression of ICAM-1 and VCAM-1, reduced the levels of MPO and MDA, and increased the content of GSH and SOD in ALI. Furthermore, IV treatment effectively increased Nrf2 and HO-1 expression in lung tissues. Therefore, IV may offer a protective role against LPS-induced ALI by inhibiting MAPK and NF-κB and activating HO-1/Nrf2 pathways.
authors.affiliation: 1. Institute of Translational Medicine, The First Hospital of Jilin University, College of Veterinary Medicine, Jilin University, Changchun, China.
authors.forename: Hongming
authors.initials: H
authors.lastname: Lv
authors.affiliation: 2. Department of Respiratory Medicine, The First Hospital of Jilin University, Changchun, China.
authors.forename: Zhenxiang
authors.initials: Z
authors.lastname: Yu
authors.affiliation: 1. Institute of Translational Medicine, The First Hospital of Jilin University, College of Veterinary Medicine, Jilin University, Changchun, China.
authors.forename: Yuwei
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: 1. Institute of Translational Medicine, The First Hospital of Jilin University, College of Veterinary Medicine, Jilin University, Changchun, China.
authors.forename: Lidong
authors.initials: L
authors.lastname: Wang
authors.affiliation: 1. Institute of Translational Medicine, The First Hospital of Jilin University, College of Veterinary Medicine, Jilin University, Changchun, China.
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Qin
authors.affiliation: 1. Institute of Translational Medicine, The First Hospital of Jilin University, College of Veterinary Medicine, Jilin University, Changchun, China.
authors.forename: Genhong
authors.initials: G
authors.lastname: Cheng
authors.affiliation: 1. Institute of Translational Medicine, The First Hospital of Jilin University, College of Veterinary Medicine, Jilin University, Changchun, China.
authors.forename: Xinxin
authors.initials: X
authors.lastname: Ci
mesh_terms: D055371:Acute Lung Injury / Q000139:chemically induced* / Q000188:drug therapy* / Q000378:metabolism; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use*; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use*; D047310:Apigenin / Q000494:pharmacology / Q000627:therapeutic use*; D002478:Cells, Cultured; D051547:Heme Oxygenase-1 / Q000378:metabolism*; D006801:Humans; D008070:Lipopolysaccharides / Q000633:toxicity; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D018384:Oxidative Stress; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D008070:Lipopolysaccharides; D051267:NF-E2-Related Factor 2; D016328:NF-kappa B; C495636:Nfe2l2 protein, mouse; D047310:Apigenin; D051547:Heme Oxygenase-1; D020928:Mitogen-Activated Protein Kinases; C049772:isovitexin
keywords: ALI; Isovitexin; LPS; inflammation; oxidative stress