Protective Effect of Piplartine against LPS-Induced Sepsis through Attenuating the MAPKs/NF-kappa B Signaling Pathway and NLRP3 Inflammasome Activation

Piplartine (or Piperlongumine) is a natural alkaloid isolated from Piper longum L., which has been proposed to exhibit various biological properties such as anti-inflammatory effects; however, the effect of piplartine on sepsis has not been examined. This study was performed to examine the anti-inflammatory activities of piplartine in vitro, ex vivo and in vivo using murine J774A.1 macrophage cell line, peritoneal macrophages, bone marrow-derived macrophages and an animal sepsis model. The results demonstrated that piplartine suppresses iNOS and COX-2 expression, reduces PGE(2), TNF-alpha and IL-6 production, decreases the phosphorylation of MAPKs and NF-kappa B and attenuates NF-kappa B activity by LPS-activated macrophages. Piplartine also inhibits IL-1 beta production and suppresses NLRP3 inflammasome activation by LPS/ATP- and LPS/nigericin-activated macrophages. Moreover, piplartine reduces the production of nitric oxide (NO) and TNF-alpha, IL-6 and IL-1 beta, decreases LPS-induced tissue damage, attenuates infiltration of inflammatory cells and enhances the survival rate. Collectively, these results demonstrate piplartine exhibits anti-inflammatory activities in LPS-induced inflammation and sepsis and suggest that piplartine might have benefits for sepsis treatment.