title: Neutral sulfate berberine modulates cytokine secretion and increases survival in endotoxemic mice.
abstract: OBJECTIVE
  Berberine is thought to be an immunomodulator, so the present study aimed to investigate the effect of berberine on mortality, lung and intestine injury in endotoxemic mice, and the mechanism of its action.
  
  
  METHODS
  Mice were challenged with lipopolysaccharide (LPS, 28 mg/kg, ip), and neutral sulfate berberine was administrated intragastrically. Mortality was monitored every 12 h, and histology of the lungs and intestine as well as the plasma tumor necrosis factor-alpha (TNF-alpha), interferon- gamma (IFN-gamma), interleukin-12 (IL-12), IL-10, and nitric oxide (NO) levels were examined.
  
  
  RESULTS
  Pretreatment with 50 mg/kg neutral sulfate berberine once a day for 5 days significantly decreased the mortality rate and attenuated tissue injury of the lungs and small intestine in mice challenged with LPS. LPS stimulated a marked increase in plasma levels of TNF-alpha, IFN- gamma, IL-12, IL-10, and NO. The administration of berberine significantly reduced plasma TNF-alpha, IFN- gamma, and NO levels, but did not suppress plasma IL-12 levels in mice exposed to LPS. Furthermore, pretreatment with neutral sulfate berberine augmented IL-10 secretion stimulated by LPS in mice.
  
  
  CONCLUSIONS
  Pretreatment with neutral sulfate berberine attenuates tissue injury and improves survival in endotoxemic mice, which may be mediated, at least in part, by the inhibition of pro-inflammatory mediator production and upregulation of IL-10 release. These findings might provide a new strategy for the treatment of endotoxemia.
authors.affiliation: Department of Pathophysiology, Medical College of Jinan University, Guangzhou 510632, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Li
authors.forename: Hua-dong
authors.initials: HD
authors.lastname: Wang
authors.forename: Da-xiang
authors.initials: DX
authors.lastname: Lu
authors.forename: Yan-ping
authors.initials: YP
authors.lastname: Wang
authors.forename: Ren-bin
authors.initials: RB
authors.lastname: Qi
authors.forename: Yong-mei
authors.initials: YM
authors.lastname: Fu
authors.forename: Chu-jie
authors.initials: CJ
authors.lastname: Li
mesh_terms: D000818:Animals; D001599:Berberine / Q000494:pharmacology*; D016207:Cytokines / Q000097:blood / Q000378:metabolism*; D019446:Endotoxemia / Q000097:blood* / Q000139:chemically induced / Q000401:mortality / Q000473:pathology; D007371:Interferon-gamma / Q000097:blood; D016753:Interleukin-10 / Q000097:blood*; D018664:Interleukin-12 / Q000097:blood; D007421:Intestine, Small / Q000473:pathology; D008070:Lipopolysaccharides; D008168:Lung / Q000473:pathology; D008297:Male; D051379:Mice; D009569:Nitric Oxide / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D016207:Cytokines; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D001599:Berberine; D016753:Interleukin-10; D018664:Interleukin-12; D009569:Nitric Oxide; D007371:Interferon-gamma