Gomisin A decreases the LPS-induced expression of iNOS and COX-2 and activation of RIP2/NF-κB in mouse peritoneal macrophages

Immunopharmacol Immunotoxicol. 2014 Jun;36(3):195-201. doi: 10.3109/08923973.2014.909848. Epub 2014 Apr 21.

Abstract

Gomisin A (GA), a lignan component contained in the fruit of Schisandra chinensis Baillon, improves hepatic cell degeneration, vasodilatory activity and insulin sensitivity. These effects also impact the immune system, including various inflammatory mediators and cytokines. In this study, the anti-inflammatory effect of GA on lipopolysaccharide-stimulated mouse peritoneal macrophages was studied. Pretreatment with GA attenuated the expression of receptor-interacting protein 2 (RIP2) and IκB kinase-β (IKK-β) as well as IKK-β phosphorylation. The activation of nuclear factor-kappa B (NF-κB) in the nucleus, the phosphorylation of IκBα and degradation of IκBα in the cytosol were suppressed by GA. GA decreased the production and mRNA expression of the inflammatory cytokines tumor necrosis factor-alpha (TNF-α) and interleukin (IL)-6. In addition, expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) and production of nitric oxide were decreased by pretreatment with GA. In conclusion, these results show that the anti-inflammatory properties of GA potentially result from the inhibition of COX-2, iNOS, IL-6, TNF-α and NO through the down-regulation of RIP2 and NF-κB activation. These results impact the development of potential health products for preventing and treating inflammatory diseases.

Keywords: Gomisin A; IKK-β; RIP2; inflammatory cytokine; peritoneal macrophages.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cyclooctanes / pharmacology*
  • Cyclooxygenase 2 / genetics*
  • Dioxoles / pharmacology*
  • I-kappa B Kinase / metabolism
  • Lignans / pharmacology*
  • Lipopolysaccharides / pharmacology*
  • Macrophages, Peritoneal / drug effects*
  • Macrophages, Peritoneal / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • NF-kappa B / metabolism*
  • Nitric Oxide Synthase Type II / genetics*
  • Receptor-Interacting Protein Serine-Threonine Kinase 2
  • Receptor-Interacting Protein Serine-Threonine Kinases / metabolism*

Substances

  • Cyclooctanes
  • Dioxoles
  • Lignans
  • Lipopolysaccharides
  • NF-kappa B
  • schizandrol B
  • Nitric Oxide Synthase Type II
  • Nos2 protein, mouse
  • Ptgs2 protein, mouse
  • Cyclooxygenase 2
  • Receptor-Interacting Protein Serine-Threonine Kinase 2
  • Receptor-Interacting Protein Serine-Threonine Kinases
  • Ripk2 protein, mouse
  • I-kappa B Kinase
  • Ikbkb protein, mouse