Abstract
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; how-ever, 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 PGE2, TNF-α and IL-6 production, decreases the phosphorylation of MAPKs and NF-κB and attenuates NF-κB activity by LPS-activated macrophages. Piplartine also inhibits IL-1β 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-α, IL-6 and IL-1β, decreases LPS-induced tissue damage, attenuates infiltration of inflammatory cells and enhances the survival rate. Collectively, these results demonstrate piplartine exhibits anti-inflam-matory activities in LPS-induced inflammation and sepsis and suggest that piplartine might have benefits for sepsis treatment.
Original language | English (US) |
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Article number | 588 |
Journal | Pharmaceuticals |
Volume | 14 |
Issue number | 6 |
DOIs | |
State | Published - Jun 2021 |
Externally published | Yes |
Keywords
- Inflammation
- Macrophage
- NLRP3 inflammasome
- Piplartine
- Sepsis
ASJC Scopus subject areas
- Molecular Medicine
- Pharmaceutical Science
- Drug Discovery