title: Role of berberine in anti-bacterial as a high-affinity LPS antagonist binding to TLR4/MD-2 receptor.
abstract: BACKGROUND
  Berberine is an isoquinoline alkaloid mainly extracted from Rhizoma Coptidis and has been shown to possess a potent inhibitory activity against bacterial. However, the role of berberine in anti-bacterial action has not been extensively studied.
  
  
  METHODS
  The animal model was established to investigate the effects of berberine on bacterial and LPS infection. Docking analysis, Molecular dynamics simulations and Real-time RT-PCR analysis was adopted to investigate the molecular mechanism.
  
  
  RESULTS
  Treatment with 40 mg/kg berberine significantly increased the survival rate of mice challenged with Salmonella typhimurium (LT2), but berberine show no effects in bacteriostasis. Further study indicated that treatment with 0.20 g/kg berberine markedly increased the survival rate of mice challenged with 2 EU/ml bacterial endotoxin (LPS) and postpone the death time of the dead mice. Moreover, pretreatment with 0.05 g/kg berberine significantly lower the increasing temperature of rabbits challenged with LPS. The studies of molecular mechanism demonstrated that Berberine was able to bind to the TLR4/MD-2 receptor, and presented higher affinity in comparison with LPS. Furthermore, berberine could significantly suppressed the increasing expression of NF-κB, IL-6, TNFα, and IFNβ in the RAW264.7 challenged with LPS.
  
  
  CONCLUSIONS
  Berberine can act as a LPS antagonist and block the LPS/TLR4 signaling from the sourse, resulting in the anti-bacterial action.
authors.affiliation: Department of Immunology, School of Basic Medical Sciences, Peking University, No,38, Xueyuan Road, Haidian District, Beijing 100191, China. famous@bjmu.edu.cn.
authors.forename: Ming
authors.initials: M
authors.lastname: Chu
authors.forename: Ran
authors.initials: R
authors.lastname: Ding
authors.forename: Zheng-yun
authors.initials: ZY
authors.lastname: Chu
authors.forename: Ming-bo
authors.initials: MB
authors.lastname: Zhang
authors.forename: Xiao-yan
authors.initials: XY
authors.lastname: Liu
authors.forename: Shao-hua
authors.initials: SH
authors.lastname: Xie
authors.forename: Yan-jun
authors.initials: YJ
authors.lastname: Zhai
authors.forename: Yue-dan
authors.initials: YD
authors.lastname: Wang
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D001599:Berberine / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D001831:Body Temperature / Q000187:drug effects; D002460:Cell Line; D016207:Cytokines / Q000378:metabolism; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors*; D051218:Lymphocyte Antigen 96 / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D056004:Molecular Dynamics Simulation; D011817:Rabbits; D012480:Salmonella Infections / Q000188:drug therapy; D012486:Salmonella typhimurium / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D051197:Toll-Like Receptor 4 / Q000378:metabolism*
chemical_list: D000900:Anti-Bacterial Agents; D016207:Cytokines; D008070:Lipopolysaccharides; D051218:Lymphocyte Antigen 96; D051197:Toll-Like Receptor 4; D001599:Berberine