title: Shikonin attenuates lipopolysaccharide-induced acute lung injury in mice.
abstract: BACKGROUND
  Shikonin, a natural naphthoquinone pigment extracted from the root of Lithospermum erythrorhizon, has shown a variety of pharmacologic properties including anti-inflammatory effect. In the present study, we analyzed the role of shikonin in acute lung injury induced by lipopolysaccharide (LPS) in mice.
  
  
  METHODS
  Sixty male BALB/C mice were randomly allocated into six groups (n = 10, each): control group, shikonin group (50 mg/kg), LPS group, and three different doses (12.5, 25, and 50 mg/kg) for shikonin-treated groups. Shikonin or vehicle was given with an intragastric administration 1 h before an intratracheal instillation of LPS (5 mg/kg). The severity of pulmonary injury was evaluated 6 h after LPS challenge.
  
  
  RESULTS
  Shikonin pretreatment significantly attenuated LPS-induced pulmonary histopathologic changes, alveolar hemorrhage, and neutrophil infiltration. The lung wet-to-dry weight ratios, as the index of pulmonary edema, were markedly decreased by shikonin pretreatment. Moreover, shikonin decreased the productions of the proinflammatory cytokines including tumor necrosis factor alpha and interleukin 1β and the concentration of total proteins in the bronchoalveolar lavage fluid. Shikonin pretreatment also reduced the concentrations of myeloperoxidase and nitric oxide in lung tissues. In addition, shikonin pretreatment significantly suppressed LPS-induced activation of cyclooxygenase 2 and inducible nitric oxide synthase and the nuclear factor κB DNA-binding activity in lung tissues.
  
  
  CONCLUSIONS
  This study indicates that shikonin may have a protective effect against LPS-induced acute lung injury, and the potential mechanism of this action may attribute partly to the inhibition of inducible nitric oxide synthase and cyclooxygenase 2 expression by downregulating nuclear factor κB activation.
authors.affiliation: Department of Thoracic Surgery, Tangdu Hospital, The Fourth Military Medical University, Xi'an, PR China.
authors.forename: Guang-Zhen
authors.initials: GZ
authors.lastname: Bai
authors.forename: Hai-Tao
authors.initials: HT
authors.lastname: Yu
authors.forename: Yun-Feng
authors.initials: YF
authors.lastname: Ni
authors.forename: Xiao-Fei
authors.initials: XF
authors.lastname: Li
authors.forename: Zhi-Pei
authors.initials: ZP
authors.lastname: Zhang
authors.forename: Kai
authors.initials: K
authors.lastname: Su
authors.forename: Jie
authors.initials: J
authors.lastname: Lei
authors.forename: Bo-Ya
authors.initials: BY
authors.lastname: Liu
authors.forename: Chang-Kang
authors.initials: CK
authors.lastname: Ke
authors.forename: Dai-Xing
authors.initials: DX
authors.lastname: Zhong
authors.forename: Yun-Jie
authors.initials: YJ
authors.lastname: Wang
authors.forename: Jin-Bo
authors.initials: JB
authors.lastname: Zhao
mesh_terms: D055371:Acute Lung Injury / Q000139:chemically induced / Q000188:drug therapy*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D051546:Cyclooxygenase 2 / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D004365:Drugs, Chinese Herbal / Q000627:therapeutic use*; D008070:Lipopolysaccharides / Q000633:toxicity; D008168:Lung / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000378:metabolism; D009285:Naphthoquinones / Q000627:therapeutic use*; D009569:Nitric Oxide / Q000032:analysis; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism; D011654:Pulmonary Edema / Q000188:drug therapy
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D004365:Drugs, Chinese Herbal; D008070:Lipopolysaccharides; D016328:NF-kappa B; D009285:Naphthoquinones; D009569:Nitric Oxide; C016101:shikonin; D004247:DNA; D009195:Peroxidase; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2