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

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 PGE(2) 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. (C) 2014 Elsevier B.V. All rights reserved.