Curcumin and its major metabolites inhibit the inflammatory response induced by lipopolysaccharide: translocation of nuclear factor-κB as potential target

Mol Med Rep. 2015 Apr;11(4):3087-93. doi: 10.3892/mmr.2014.3079. Epub 2014 Dec 11.

Abstract

The aim of the present study was to investigate and compare the anti‑inflammatory activities of curcumin and its three metabolites, tetrahydrocurcumin, hexahydrocurcumin and octahydrocurcumin in lipopolysaccharide (LPS)‑stimulated RAW 264.7 macrophage cells. The results demonstrated that overproduction of nitric oxide (NO) was potently inhibited following treatment with curcumin and its three metabolites. In addition, curcumin and tetrahydrocurcumin significantly inhibited the release of prominent cytokines, including tumor necrosis factor‑α (TNF‑α) and interleukin‑6 (IL‑6); however, hexahydrocurcumin and octahydrocurcumin did not significantly alter cytokine release. Furthermore, the present study investigated the effect of curcumin and its metabolites on the expression of inducible NO synthase (iNOS), cyclooxygenase‑2 (COX‑2) and activated‑nuclear factor kappa B (NF‑κB); the results showed that curcumin and its three metabolites significantly inhibited LPS‑mediated upregulation of iNOS and COX‑2 as well as NF‑κB activation. However, curcumin exerted a more potent effect on LPS‑stimulated RAW 264.7 cells compared to that of its three metabolites, of which tetrahydrocurcuim was found to be the most pharmacologically active. In conclusion, the results of the present study demonstrated that curcumin and its major metabolites inhibited the LPS‑induced inflammatory response via the mechanism of inhibiting NF‑κB translocation to the nucleus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / chemistry
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Cell Line
  • Cell Survival / drug effects
  • Curcumin / analogs & derivatives*
  • Curcumin / chemistry
  • Curcumin / pharmacology*
  • Cyclooxygenase 2 / genetics
  • Cyclooxygenase 2 / metabolism
  • Cytokines / metabolism
  • Lipopolysaccharides / immunology
  • Macrophages / drug effects*
  • Macrophages / immunology
  • Macrophages / metabolism*
  • Male
  • Mice
  • NF-kappa B / metabolism
  • Nitric Oxide / metabolism
  • Nitric Oxide Synthase Type II / genetics
  • Nitric Oxide Synthase Type II / metabolism
  • Protein Transport
  • Proteolysis
  • Rats

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Cytokines
  • Lipopolysaccharides
  • NF-kappa B
  • hexahydrocurcumin
  • tetrahydrocurcumin
  • Nitric Oxide
  • Nitric Oxide Synthase Type II
  • Cyclooxygenase 2
  • Curcumin