title: Suppression of MAPK and NF-κB pathways by limonene contributes to attenuation of lipopolysaccharide-induced inflammatory responses in acute lung injury.
abstract: The present study aimed to investigate the protective role of limonene in lipopolysaccharide (LPS)-induced acute lung injury (ALI). ALI was induced in mice by intratracheal instillation of LPS (0.5 mg/kg), and limonene (25, 50, and 75 mg/kg) was injected intraperitoneally 1 h prior to LPS administration. After 12 h, bronchoalveolar lavage fluid (BALF) and lung tissue were collected. Limonene pretreatment at doses of 25, 50, and 75 mg/kg decreased LPS-induced evident lung histopathological changes, lung wet-to-dry weight ratio, and lung myeloperoxidase activity. In addition, pretreatment with limonene inhibited inflammatory cells and proinflammatory cytokines including tumor necrosis factor-α, interleukin-1β, and interleukin-6 in BALF. Furthermore, we demonstrated that limonene blocked the phosphorylation of IκBα, nuclear factor-κB (NF-κB) p65, p38 mitogen-activated protein kinase (MAPK), c-Jun NH2-terminal kinase, and extracellular signal-regulated kinase in LPS-induced ALI. The results presented here suggest that the protective mechanism of limonene may be attributed partly to decreased production of proinflammatory cytokines through the inhibition of NF-κB and MAPK activation.
authors.affiliation: 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.forename: Miaomiao
authors.initials: M
authors.lastname: Wei
authors.forename: Xianxing
authors.initials: X
authors.lastname: Xie
authors.forename: L W
authors.initials: LW
authors.lastname: Soromou
authors.forename: Fang
authors.initials: F
authors.lastname: Liu
authors.forename: Shuhua
authors.initials: S
authors.lastname: Zhao
mesh_terms: D055371:Acute Lung Injury / Q000188:drug therapy* / Q000276:immunology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D001992:Bronchoalveolar Lavage Fluid; D053138:Cyclohexenes / Q000494:pharmacology*; D003907:Dexamethasone / Q000494:pharmacology; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy; D007378:Interleukins / Q000378:metabolism; D000077222:Limonene; D008070:Lipopolysaccharides; D008168:Lung / Q000276:immunology / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000378:metabolism; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D052002:NF-kappa B p50 Subunit / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D013729:Terpenes / Q000494:pharmacology*; D051996:Transcription Factor RelA / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D053138:Cyclohexenes; D007378:Interleukins; D008070:Lipopolysaccharides; D016328:NF-kappa B; D052002:NF-kappa B p50 Subunit; C498144:Rela protein, mouse; D013729:Terpenes; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; C073701:Nfkb1 protein, mouse; D003907:Dexamethasone; D000077222:Limonene; D009195:Peroxidase; D020928:Mitogen-Activated Protein Kinases