title: A novel imidazopyridine derivative, X22, attenuates sepsis-induced lung and liver injury by inhibiting the inflammatory response in vitro and in vivo.
abstract: Sepsis remains a leading cause of death worldwide. Despite years of extensive research, effective drugs to treat sepsis in the clinic are lacking. In this study, we found a novel imidazopyridine derivative, X22, which has powerful anti-inflammatory activity. X22 dose-dependently inhibited lipopolysaccharide (LPS)-induced proinflammatory cytokine production in mouse primary peritoneal macrophages and RAW 264.7 macrophages. X22 also downregulated the LPS-induced proinflammatory gene expression in vitro. In vivo, X22 exhibited a significant protection against LPS-induced death. Pretreatment or treatment with X22 attenuated the sepsis-induced lung and liver injury by inhibiting the inflammatory response. In addition, X22 showed protection against LPS-induced acute lung injury. We additionally found that pretreatment with X22 reduced the inflammatory pain in the acetic acid and formalin models and reduced the dimethylbenzene-induced ear swelling and acetic acid-increased vascular permeability. Together, these data confirmed that X22 has multiple anti-inflammatory effects and may be a potential therapeutic option in the treatment of inflammatory diseases.
authors.affiliation: Chemical Biology Research Center, School of Pharmaceutical Sciences; Department of Pulmonary Medicine, The 2nd Affiliated Hospital.
authors.forename: Xiangting
authors.initials: X
authors.lastname: Ge
authors.affiliation: Chemical Biology Research Center, School of Pharmaceutical Sciences.
authors.forename: Zhiguo
authors.initials: Z
authors.lastname: Feng
authors.affiliation: Department of Pulmonary Medicine, The 2nd Affiliated Hospital.
authors.forename: Tingting
authors.initials: T
authors.lastname: Xu
authors.affiliation: Department of Pediatrics, The 2nd Affiliated Hospital, Wenzhou Medical University, Wenzhou, People's Republic of China.
authors.forename: Beibei
authors.initials: B
authors.lastname: Wu
authors.affiliation: Chemical Biology Research Center, School of Pharmaceutical Sciences.
authors.forename: Hongjin
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Pediatrics, The 2nd Affiliated Hospital, Wenzhou Medical University, Wenzhou, People's Republic of China.
authors.forename: Fengli
authors.initials: F
authors.lastname: Xu
authors.affiliation: Chemical Biology Research Center, School of Pharmaceutical Sciences.
authors.forename: Lili
authors.initials: L
authors.lastname: Fu
authors.affiliation: Department of Pediatrics, The 2nd Affiliated Hospital, Wenzhou Medical University, Wenzhou, People's Republic of China.
authors.forename: Xiaoou
authors.initials: X
authors.lastname: Shan
authors.affiliation: Department of Pulmonary Medicine, The 2nd Affiliated Hospital.
authors.forename: Yuanrong
authors.initials: Y
authors.lastname: Dai
authors.affiliation: Chemical Biology Research Center, School of Pharmaceutical Sciences.
authors.forename: Yali
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Chemical Biology Research Center, School of Pharmaceutical Sciences.
authors.forename: Guang
authors.initials: G
authors.lastname: Liang
mesh_terms: D055371:Acute Lung Injury / Q000188:drug therapy* / Q000378:metabolism; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000494:pharmacology*; D016207:Cytokines / Q000737:chemistry / Q000378:metabolism*; D007093:Imidazoles / Q000737:chemistry / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors* / Q000737:chemistry*; D008099:Liver; D017737:Macrophages, Peritoneal / Q000737:chemistry / Q000187:drug effects*; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D011725:Pyridines / Q000737:chemistry / Q000494:pharmacology*; D018805:Sepsis / Q000188:drug therapy* / Q000503:physiopathology*; D014992:Xylenes / Q000737:chemistry* / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D007093:Imidazoles; D008070:Lipopolysaccharides; D016328:NF-kappa B; D011725:Pyridines; C000600451:X22 compound; D014992:Xylenes
keywords: LPS; acute lung injury; imidazopyridine derivative; inflammation; sepsis