Capsaicin exhibits anti-inflammatory property by inhibiting IkB-a degradation in LPS-stimulated peritoneal macrophages

Cell Signal. 2003 Mar;15(3):299-306. doi: 10.1016/s0898-6568(02)00086-4.


Capsaicin, a major ingredient of hot pepper, was considered to exhibit an anti-inflammatory property. In order to clarify the signalling mechanism underlying the anti-inflammatory action of capsaicin, we investigated the effect of capsaicin on the production of inflammatory molecules in lipopolysaccharide (LPS)-stimulated murine peritoneal macrophages. The level of PGE2 was measured by EIA. The expression levels of COX-2, iNOS, IkB-a, and vanilloid receptor-1 (VR-1) were determined at the protein and mRNA levels. Significant inhibition of the production of LPS-induced PGE2 by capsaicin was observed in a dose-dependent manner. Capsaicin did not affect the COX-2 expression at either the protein or mRNA level, but inhibited the enzyme activity of COX-2 and the expression of the iNOS protein. Capsaicin completely blocked LPS-induced disappearance of IkB-a and therefore inactivated NF-kB. The inhibitory action of capsaicin on PGE2 production was not abolished by capsazepine, a specific antagonist to VR-1. A high expression level of the VR-1 like protein (VRL-1) was observed in peritoneal macrophages, while the expression of VR-1 was not detected. These findings suggest that the anti-inflammatory action of capsaicin may occur through a novel mechanism, not by a VR-1 receptor-mediated one. Both capsaicin and capsazepine may be a promising drug candidates for ameliorating inflammatory diseases and cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Capsaicin / pharmacology*
  • Cyclooxygenase 2
  • Dinoprostone / metabolism
  • Enzyme Activation / drug effects
  • Gene Expression Regulation, Enzymologic
  • I-kappa B Proteins / metabolism*
  • Isoenzymes / genetics
  • Isoenzymes / metabolism
  • Lipopolysaccharides / pharmacology*
  • Macrophages, Peritoneal / drug effects*
  • Macrophages, Peritoneal / immunology
  • Macrophages, Peritoneal / metabolism*
  • Mice
  • Mice, Inbred BALB C
  • Nitric Oxide / metabolism
  • Nitric Oxide Synthase / genetics
  • Nitric Oxide Synthase / metabolism
  • Nitric Oxide Synthase Type II
  • Prostaglandin-Endoperoxide Synthases / genetics
  • Prostaglandin-Endoperoxide Synthases / metabolism
  • RNA, Messenger / analysis
  • Receptors, Drug / genetics
  • Receptors, Drug / metabolism
  • TRPV Cation Channels


  • Anti-Inflammatory Agents
  • I-kappa B Proteins
  • Isoenzymes
  • Lipopolysaccharides
  • RNA, Messenger
  • Receptors, Drug
  • TRPV Cation Channels
  • TRPV1 receptor
  • Nitric Oxide
  • Nitric Oxide Synthase
  • Nitric Oxide Synthase Type II
  • Nos2 protein, mouse
  • Cyclooxygenase 2
  • Prostaglandin-Endoperoxide Synthases
  • Dinoprostone
  • Capsaicin