Protective effect of piplartine against lps-induced sepsis through attenuating the mapks/nf-κb signaling pathway and nlrp3 inflammasome activation

Chi Han Huang, Shu Chi Wang, I. Chen Chen, Yi Ting Chen, Po Len Liu, Shih Hua Fang, Shu Pin Huang, Hsin Chih Yeh, Ching Chih Liu, Po Yen Lee, Tzu Chieh Lin, Wei Chung Cheng, Chia Cheng Su, Hsin En Wu, Yuan Ru Chen, Chia Yang Li

Research output: Contribution to journalArticlepeer-review

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 languageEnglish (US)
Article number588
JournalPharmaceuticals
Volume14
Issue number6
DOIs
StatePublished - Jun 2021

Keywords

  • Inflammation
  • Macrophage
  • NLRP3 inflammasome
  • Piplartine
  • Sepsis

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmaceutical Science
  • Drug Discovery

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