Inhibition of lipopolysaccharide-induced inflammatory responses by piperine

Eur J Pharmacol. 2010 Sep 10;642(1-3):154-62. doi: 10.1016/j.ejphar.2010.05.026. Epub 2010 Jun 8.


Piperine, a main component of Piper longum Linn. and Piper nigrum Linn., is a plant alkaloid with a long history of medical use. Piperine exhibits anti-inflammatory activity; however, the underlying mechanism remains unknown. We examined the effects of piperine on lipopolysaccharide (LPS)-induced inflammatory responses. Administration of piperine inhibited LPS-induced endotoxin shock, leukocyte accumulation and the production of tumor necrosis factor-alpha (TNF-alpha), but not of interleukin (IL)-1beta and IL-6. In peritoneal macrophages, piperine inhibited LPS/poly (I:C)/CpG-ODN-induced TNF-alpha production. Piperine also inhibited LPS-induced endotoxin shock in TNF-alpha knockout (KO) mice. To clarify the inhibitory mechanism of LPS-induced endotoxin shock, type 1 interferon (IFN) mRNA expression was determined. Piperine inhibited LPS-induced expression of type 1 IFN mRNA. Piperine inhibited the levels of interferon regulatory factor (IRF)-1 and IRF-7 mRNA, and the phosphorylation and nuclear translocation of IRF-3. Piperine also reduced activation of signal transducer and activator of transcription (STAT)-1. In addition, activation of STAT-1 was inhibited in IFN-alpha/beta-treated cells by piperine. These results suggest that piperine inhibits LPS-induced endotoxin shock through inhibition of type 1 IFN production.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkaloids / pharmacology*
  • Alkaloids / therapeutic use
  • Animals
  • Benzodioxoles / pharmacology*
  • Benzodioxoles / therapeutic use
  • Female
  • Gene Knockout Techniques
  • Inflammation / drug therapy*
  • Inflammation / immunology
  • Inflammation / metabolism
  • Interferon Type I / biosynthesis
  • Lipopolysaccharides / pharmacology*
  • Macrophages, Peritoneal / drug effects
  • Macrophages, Peritoneal / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Piperidines / pharmacology*
  • Piperidines / therapeutic use
  • Polyunsaturated Alkamides / pharmacology*
  • Polyunsaturated Alkamides / therapeutic use
  • STAT1 Transcription Factor / metabolism
  • Shock, Septic / drug therapy
  • Tumor Necrosis Factor-alpha / deficiency
  • Tumor Necrosis Factor-alpha / genetics


  • Alkaloids
  • Benzodioxoles
  • Interferon Type I
  • Lipopolysaccharides
  • Piperidines
  • Polyunsaturated Alkamides
  • STAT1 Transcription Factor
  • Tumor Necrosis Factor-alpha
  • piperine