The α-cyclodextrin complex of the Moringa isothiocyanate suppresses lipopolysaccharide-induced inflammation in RAW 264.7 macrophage cells through Akt and p38 inhibition

Inflamm Res. 2017 Jun;66(6):487-503. doi: 10.1007/s00011-017-1033-7. Epub 2017 Mar 13.

Abstract

In the last decades, a growing need to discover new compounds for the prevention and treatment of inflammatory diseases has led researchers to consider drugs derived from natural products as a valid option in the treatment of inflammation-associated disorders. The purpose of the present study was to investigate the anti-inflammatory effects of a new formulation of Moringa oleifera-derived 4-(α-L-rhamnopyranosyloxy)benzyl isothiocyanate as a complex with alpha-cyclodextrin (moringin + α-CD) on lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophage cells, a common model used for inflammation studies. In buffered/aqueous solution, the moringin + α-CD complex has enhanced the water solubility and stability of this isothiocyanate by forming a stable inclusion system. Our results showed that moringin + α-CD inhibits the production of inflammatory mediators in LPS-stimulated macrophages by down-regulation of pro-inflammatory cytokines (TNF-α and IL-1β), by preventing IκB-α phosphorylation, translocation of the nuclear factor-κB (NF-κB), and also via the suppression of Akt and p38 phosphorylation. In addition, as a consequence of upstream inhibition of the inflammatory pathway following treatment with moringin + α-CD, the modulation of the oxidative stress (results focused on the expression of iNOS and nitrotyrosine) and apoptotic pathway (Bax and Bcl-2) was demonstrated. Therefore, moringin + α-CD appears to be a new relevant helpful tool to use in clinical practice for inflammation-associated disorders.

Keywords: Akt; Inflammation; Moringa isothiocyanate; P38; RAW 264.7 macrophage cells; α-CD-complexed moringin.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / chemistry
  • Anti-Inflammatory Agents / pharmacology*
  • Inflammation / metabolism
  • Interleukin-1beta / metabolism
  • Isothiocyanates / chemistry
  • Isothiocyanates / pharmacology*
  • Lipopolysaccharides
  • Mice
  • Moringa*
  • NF-KappaB Inhibitor alpha / metabolism
  • NF-kappa B / metabolism
  • Proto-Oncogene Proteins c-akt / antagonists & inhibitors
  • RAW 264.7 Cells
  • Tumor Necrosis Factor-alpha / metabolism
  • alpha-Cyclodextrins / chemistry
  • alpha-Cyclodextrins / pharmacology*
  • p38 Mitogen-Activated Protein Kinases / antagonists & inhibitors

Substances

  • Anti-Inflammatory Agents
  • IL1B protein, mouse
  • Interleukin-1beta
  • Isothiocyanates
  • Lipopolysaccharides
  • NF-kappa B
  • Tumor Necrosis Factor-alpha
  • alpha-Cyclodextrins
  • moringin
  • NF-KappaB Inhibitor alpha
  • Proto-Oncogene Proteins c-akt
  • p38 Mitogen-Activated Protein Kinases
  • alpha-cyclodextrin