title: The natural product bergenin ameliorates lipopolysaccharide-induced acute lung injury by inhibiting NF-kappaB activition.
abstract: BACKGROUND
  Bergenin, an active constituent of the plants of the genus Bergenia, was reported to have anti-inflammatory effects in the treatment of chronic bronchitis and chronic gastritis clinically. However, its therapeutic effect on lipopolysaccharide (LPS)-induced acute lung injury (ALI) and its potential mechanisms of actions were still unknown.
  
  
  OBJECTIVE
  To evaluate the effect of bergenin on murine model of acute lung injury induced by LPS and also to explore its potential mechanisms.
  
  
  METHODS
  Half an hour and 12h after an intranasal inhalation of LPS, male BALB/c mice were treated with bergenin (50,100 and 200mg/kg) or dexamethasone (DEX, 5mg/kg) by gavage. Twenty-four hours after LPS exposure, the lung wet/dry ratio, histological changes, myeloperoxidase (MPO) in lung tissues, inflammatory cells (in BALF) and cytokines (in BALF and serum) were detected. Meanwhile, the protein expression of MyD88 and the phosphorylation of NF-κB p65 in lung tissue were analyzed using immunoblot analysis. Moreover, the nuclear translocation and the phosphorylation of NF-κB p65 in Raw264.7 cells were also analyzed. The viability of Raw264.7 cells was determined by MTT assay.
  
  
  RESULTS
  Results showed that bergenin significantly decreased pulmonary edema, improved histological changes and reduced MPO activity in lung tissues. Moreover, bergenin obviously decreased inflammatory cells, IL-1β and IL-6 production in BALF, as well as IL-1β, TNF-α and IL-6 production in serum of LPS-induced ALI mice. Furthermore, bergenin markedly inhibited LPS-induced NF-κB p65 phosphorylation, as well as the expression of MyD88 but not the expression of NF-κB p65 in lung tissues. Additionally, bergenin also significantly inhibited the nuclear translocation and the phosphorylation of NF-κB p65 stimulated by LPS in Raw264.7 cells.
  
  
  CONCLUSIONS
  These findings suggested that bergenin had a therapeutic effect on LPS-induced ALI by inhibiting NF-κB activition.
authors.affiliation: Beijing Key Laboratory of Drug Target Identification, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, PR China. Electronic address: saintchyang@yahoo.com.
authors.forename: Shengqian
authors.initials: S
authors.lastname: Yang
authors.affiliation: Beijing Key Laboratory of Drug Target Identification, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, PR China. Electronic address: yuziru@imm.ac.cn.
authors.forename: Ziru
authors.initials: Z
authors.lastname: Yu
authors.affiliation: Beijing Key Laboratory of Drug Target Identification, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, PR China. Electronic address: wanglinster@imm.ac.cn.
authors.forename: Lin
authors.initials: L
authors.lastname: Wang
authors.affiliation: Beijing Key Laboratory of Drug Target Identification, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, PR China. Electronic address: yuantianyi@imm.ac.cn.
authors.forename: Tianyi
authors.initials: T
authors.lastname: Yuan
authors.affiliation: Xinjiang Key Laboratory for Uighur Medicine, Institute of Materia Medica of Xinjiang, Urumqi 830004, PR China. Electronic address: axtwx2005@126.com.
authors.forename: Xue
authors.initials: X
authors.lastname: Wang
authors.affiliation: Beijing Key Laboratory of Drug Target Identification, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, PR China. Electronic address: xuezhang@imm.ac.cn.
authors.forename: Xue
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Beijing Key Laboratory of Drug Target Identification, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, PR China. Electronic address: wjh@imm.ac.cn.
authors.forename: Jinhua
authors.initials: J
authors.lastname: Wang
authors.affiliation: Beijing Key Laboratory of Drug Crystal Research, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, PR China. Electronic address: luy@imm.ac.cn.
authors.forename: Yang
authors.initials: Y
authors.lastname: Lv
authors.affiliation: Beijing Key Laboratory of Drug Target Identification, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, PR China. Electronic address: dugh@imm.ac.cn.
authors.forename: Guanhua
authors.initials: G
authors.lastname: Du
mesh_terms: D055371:Acute Lung Injury / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology / Q000627:therapeutic use*; D001688:Biological Products / Q000494:pharmacology / Q000627:therapeutic use*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D008070:Lipopolysaccharides / Q000633:toxicity*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011897:Random Allocation
chemical_list: D001578:Benzopyrans; D001688:Biological Products; D008070:Lipopolysaccharides; D016328:NF-kappa B; C006741:bergenin
keywords: Acute lung injury; Bergenin; Bergenin (PubChem CID: 66065); Dexamethasone (PubChem CID:5743); Inflammation; Lipopolysaccharide; MyD88; NF-κB