title: Berberine protects against lipopolysaccharide-induced intestinal injury in mice via alpha 2 adrenoceptor-independent mechanisms.
abstract: OBJECTIVE
  To investigate the mechanisms responsible for the protective action of berberine (Ber) against gut damage in endotoxemic mice.
  
  
  METHODS
  Male BALB/c mice were administered intragastrically with distilled water (0.1 mL/10 g), Ber (50 mg/kg) alone, yohimbine (2 mg/kg) alone, or Ber (50 mg/kg) in combination with yohimbine (2 mg/kg) for 3 d. On the third day, lipopolysaccharide (LPS, 18 mg/kg) or normal saline was intraperitoneally injected one hour after the intragastric administration. Following the treatment, intestinal injury in the ileum was histopathologically accessed; enterocyte apoptosis was examined using TUNEL method; Toll-like receptor 4 (TLR4) mRNA expression was measured using RT-PCR assay; inhibitor protein-κBα (I-κBα) phosphorylation and myeloperoxidase content were examined using Western blloting. The macrophage inflammatory protein-2 (MIP-2) production was measured using ELISA assay.
  
  
  RESULTS
  Mice challenged with LPS caused extensive ileum injury, including a significantly increased injury score, decreased intestinal villus height, reduced gut mucosal weight and increased intestinal permeability. Furthermore, LPS significantly induced enterocyte apoptosis, increased TLR4 mRNA expression, I-κBα phosphorylation, MIP-2 production and myeloperoxidase content in the ileum. Pretreatment with Ber significantly alleviated all the alterations in the ileum in the endotoxemic mice. Pretreatment with the α2-adrenoceptor antagonist yohimbine did not block the protective action of Ber against LPS-induced intestinal injury. In addition, treatment with yohimbine alone did not prevent LPS-induced intestinal injury.
  
  
  CONCLUSIONS
  Pretreatment with Ber provides significant protection against LPS-induced intestinal injury in mice, via reducing enterocyte apoptosis, inhibiting the TLR4-nuclear factor κB-MIP-2 pathway and decreasing neutrophil infiltration that are independent of α2-adrenoceptors.
authors.affiliation: Department of Pathophysiology, Key Laboratory of State Administration of Traditional Chinese Medicine, School of Medicine, Ji-nan University, Guangzhou, China.
authors.forename: Hong-mei
authors.initials: HM
authors.lastname: Li
authors.forename: Yi-yang
authors.initials: YY
authors.lastname: Wang
authors.forename: Hua-dong
authors.initials: HD
authors.lastname: Wang
authors.forename: Wen-juan
authors.initials: WJ
authors.lastname: Cao
authors.forename: Xiao-hui
authors.initials: XH
authors.lastname: Yu
authors.forename: Da-xiang
authors.initials: DX
authors.lastname: Lu
authors.forename: Ren-bin
authors.initials: RB
authors.lastname: Qi
authors.forename: Chao-feng
authors.initials: CF
authors.lastname: Hu
authors.forename: Yu-xia
authors.initials: YX
authors.lastname: Yan
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001599:Berberine / Q000494:pharmacology / Q000627:therapeutic use*; D054426:Chemokine CXCL2 / Q000276:immunology; D000089042:Coptis chinensis; D004365:Drugs, Chinese Herbal / Q000737:chemistry*; D019446:Endotoxemia / Q000139:chemically induced / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D020895:Enterocytes / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D005786:Gene Expression Regulation / Q000187:drug effects; D007082:Ileum / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D008070:Lipopolysaccharides / Q000009:adverse effects* / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000276:immunology; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D018341:Receptors, Adrenergic, alpha-2 / Q000276:immunology; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000276:immunology; D015016:Yohimbine / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D054426:Chemokine CXCL2; C404915:Cxcl2 protein, mouse; D004365:Drugs, Chinese Herbal; D008070:Lipopolysaccharides; D016328:NF-kappa B; D018341:Receptors, Adrenergic, alpha-2; D051197:Toll-Like Receptor 4; D001599:Berberine; D015016:Yohimbine; C107393:Coptidis rhizoma extract