title: Isotetrandrine protects against lipopolysaccharide-induced acute lung injury by suppression of mitogen-activated protein kinase and nuclear factor-kappa B.
abstract: BACKGROUND
  Mitogen-activated protein kinases (MAPKs) and nuclear factor-kappa B (NF-κB) signaling pathways are pleiotropic regulator of many genes involved in lipopolysaccharide (LPS)-induced acute lung injury (ALI). The present study aimed to reveal the protective effect of isotetrandrine (ITD), a small molecule inhibitor, on various aspects of LPS-induced inflammation in vitro and in vivo.
  
  
  METHODS
  In vitro, RAW 264.7 cells were pretreated with different dose of ITD 1 h before treatment with 1 mg/L of LPS. In vivo, to induce ALI, male BALB/c mice were injected intranasally with LPS and treated with ITD (20 and 40 mg/kg) 1 h before LPS.
  
  
  RESULTS
  In vitro, the cytokine levels of tumor necrosis factor-α, interleukin (IL)-1β, and IL-6 in supernatant were reduced by ITD. Meanwhile, in vivo, pulmonary inflammatory cell infiltration, myeloperoxidase activity, total cells, neutrophils, macrophages, along with the levels of tumor necrosis factor-α, IL-1β, and IL-6 in bronchoalveolar lavage fluid were dose-dependently attenuated by ITD. Furthermore, our data showed that ITD significantly inhibited the activation of MAPK and NF-κB, which are induced by LPS in ALI model.
  
  
  CONCLUSIONS
  These results suggested that ITD dose-dependently suppressed the severity of LPS-induced ALI by inactivation of MAPK and NF-κB, which may involve the inhibition of tissue oxidative injury and pulmonary inflammatory process.
authors: National Reference Laboratory of Veterinary Drug Residues (SCAU), College of Veterinary Medicine, South China Agricultural University, Guangzhou, People's Republic of China; The Department of Chemical Drug Review, China Institute of Veterinary Drugs Control, Beijing, People's Republic of China.
authors: Xian-ming
authors: XM
authors: Liang
authors: The Department of Chemical Drug Review, China Institute of Veterinary Drugs Control, Beijing, People's Republic of China.
authors: Gui-fang
authors: GF
authors: Guo
authors: National Reference Laboratory of Veterinary Drug Residues (SCAU), College of Veterinary Medicine, South China Agricultural University, Guangzhou, People's Republic of China.
authors: Xian-hui
authors: XH
authors: Huang
authors: The Department of Chemical Drug Review, China Institute of Veterinary Drugs Control, Beijing, People's Republic of China.
authors: Wen-long
authors: WL
authors: Duan
authors: National Reference Laboratory of Veterinary Drug Residues (SCAU), College of Veterinary Medicine, South China Agricultural University, Guangzhou, People's Republic of China. Electronic address: zlzeng@scau.edu.cn.
authors: Zhen-ling
authors: ZL
authors: Zeng
mesh_terms: D055371:Acute Lung Injury / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D000818:Animals; D044182:Benzylisoquinolines / Q000737:chemistry / Q000494:pharmacology*; D001992:Bronchoalveolar Lavage Fluid; D002460:Cell Line; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D007166:Immunosuppressive Agents / Q000737:chemistry / Q000494:pharmacology*; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D009195:Peroxidase / Q000378:metabolism; D011654:Pulmonary Edema / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism
chemical_list: D044182:Benzylisoquinolines; C587672:IL1B protein, mouse; D007166:Immunosuppressive Agents; D053583:Interleukin-1beta; D015850:Interleukin-6; D008070:Lipopolysaccharides; D016328:NF-kappa B; C577686:interleukin-6, mouse; C009438:tetrandrine; D009195:Peroxidase; D020928:Mitogen-Activated Protein Kinases
keywords: ALI; Inflammation; Isotetrandrine (ITD); LPS