title: Protective effect of sanguinarine on LPS-induced endotoxic shock in mice and its effect on LPS-induced COX-2 expression and COX-2 associated PGE2 release from peritoneal macrophages.
abstract: The quaternary ammonium salt, sanguinarine (SG) was reported to possess widespread anti-microbial and anti-inflammatory effects in experimental animals and it has been used to treat many inflammatory diseases. The aim of this study was to evaluate the anti-inflammatory effect and the possible mechanisms underlying the anti-inflammatory activity of SG. Experimentally-induced mice ES model and LPS-induced peritoneal macrophages were used to examine the anti-inflammatory function of SG. In this study, SG pretreatment significantly increased the survival rate of mice from 25% to 58%, 75% and 91% respectively. The production of PGE2 in BALF, the lung MPO activity and the (W/D) weight ratios were also markedly reduced. In addition, immunohistochemical analysis showed that the expression of COX-2 was significantly suppressed in vivo. We also evaluated the effect of SG in LPS-induced peritoneal macrophages to clarify the possible mechanism. The data indicated that SG greatly inhibited the production of PGE2, and it also decreased COX-2 protein expression, without affecting COX-1 expression, in LPS-stimulated peritoneal macrophages. Taken all together, SG potently protected against LPS-induced ES, and our results suggest that the possible mechanism may be relevant to COX-2 regulation.
authors: School of Pharmacy, Xi'an Jiaotong University, Xi'an 710061, PR China. Electronic address: liwf@mail.xjtu.edu.cn.
authors: Weifeng
authors: W
authors: Li
authors: School of Pharmacy, Xi'an Jiaotong University, Xi'an 710061, PR China.
authors: Huani
authors: H
authors: Li
authors: School of Pharmacy, Xi'an Jiaotong University, Xi'an 710061, PR China.
authors: Qingli
authors: Q
authors: Mu
authors: School of Pharmacy, Xi'an Jiaotong University, Xi'an 710061, PR China.
authors: Hailin
authors: H
authors: Zhang
authors: School of Pharmacy, Xi'an Jiaotong University, Xi'an 710061, PR China.
authors: Huan
authors: H
authors: Yao
authors: School of Pharmacy, Xi'an Jiaotong University, Xi'an 710061, PR China.
authors: Jiaoshe
authors: J
authors: Li
authors: School of Pharmacy, Xi'an Jiaotong University, Xi'an 710061, PR China. Electronic address: niuxf@mail.xjtu.edu.cn.
authors: Xiaofeng
authors: X
authors: Niu
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology* / Q000627:therapeutic use; D053119:Benzophenanthridines / Q000494:pharmacology* / Q000627:therapeutic use; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D051546:Cyclooxygenase 2 / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D005260:Female; D007546:Isoquinolines / Q000494:pharmacology* / Q000627:therapeutic use; D008070:Lipopolysaccharides; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D017737:Macrophages, Peritoneal / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D009195:Peroxidase / Q000378:metabolism; D012772:Shock, Septic / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology
chemical_list: D000893:Anti-Inflammatory Agents; D053119:Benzophenanthridines; D007546:Isoquinolines; D008070:Lipopolysaccharides; C005705:sanguinarine; D009195:Peroxidase; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D015232:Dinoprostone
keywords: Cyclooxygenase-2; Endotoxic shock; Lipopolysaccharide; Peritoneal macrophages; Prostaglandin (PG) E(2); Sanguinarine