Indole-containing fractions of Brassica rapa inhibit inducible nitric oxide synthase and pro-inflammatory cytokine expression by inactivating nuclear factor-κB

J Med Food. 2011 Dec;14(12):1527-37. doi: 10.1089/jmf.2011.1611. Epub 2011 Aug 30.

Abstract

In an attempt to identify bioactive natural products with anti-inflammatory activity, we evaluated the anti-inflammatory potential of the indole-containing fraction from the roots of Brassica rapa (IBR) (Family Brassicaceae) and the underlying mechanisms. Initially, we examined the inhibitory effect of IBR on the production of pro-inflammatory mediators in vitro and then evaluated its in vivo anti-inflammatory effects. IBR was found to concentration-dependently reduce the productions of nitric oxide, tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) in lipopolysaccharide (LPS)-induced macrophages. Consistent with these findings, IBR suppressed the LPS-induced expressions of inducible nitric oxide synthase (iNOS) at the protein level and of iNOS, TNF-α, and IL-6 at the mRNA level. Furthermore, IBR attenuated LPS-induced DNA-binding activities of nuclear factor-κB (NF-κB), and this was accompanied by a parallel reduction in the degradation and phosphorylation of inhibitory κBα and, consequently, by a reduction in the nuclear translocation of the p65 subunit of NF-κB. In addition, treatment with IBR inhibited carrageenan-induced paw edema in rats and acetic acid-induced writing response in mice. Taken together, our data suggest that the expressional inhibitions of iNOS, TNF-α, and IL-6 caused by an attenuation of NF-κB activation are responsible for the anti-inflammatory and antinociceptive activity of IBR.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Brassica rapa / chemistry*
  • Cell Line
  • Cyclooxygenase 2 / genetics
  • Cyclooxygenase 2 / metabolism
  • Dinoprostone / antagonists & inhibitors
  • Dinoprostone / blood
  • Gene Expression Regulation
  • Humans
  • Indoles / pharmacology*
  • Interleukin-6 / antagonists & inhibitors
  • Interleukin-6 / blood
  • Lipopolysaccharides / metabolism
  • Male
  • Mice
  • Mice, Inbred ICR
  • NF-kappa B / antagonists & inhibitors*
  • NF-kappa B / genetics
  • NF-kappa B / metabolism
  • Nitric Oxide Synthase Type II / antagonists & inhibitors*
  • Nitric Oxide Synthase Type II / genetics
  • Nitric Oxide Synthase Type II / metabolism
  • Phosphorylation / drug effects
  • Plant Extracts / pharmacology*
  • Plant Roots / chemistry
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors
  • Tumor Necrosis Factor-alpha / blood

Substances

  • Anti-Inflammatory Agents
  • Indoles
  • Interleukin-6
  • Lipopolysaccharides
  • NF-kappa B
  • Plant Extracts
  • RNA, Messenger
  • Tumor Necrosis Factor-alpha
  • Nitric Oxide Synthase Type II
  • Nos2 protein, mouse
  • Ptgs2 protein, mouse
  • Cyclooxygenase 2
  • Dinoprostone