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

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.

• Authors: Sabrina Giacoppo, Thangavelu Soundara Rajan, Renato Iori, Patrick Rollin, Placido Bramanti, Emanuela Mazzon
• Journal: Inflammation research : official journal of the European Histamine Research Society ... [et al.] (Inflamm Res) Vol. 66 Issue 6 Pg. 487-503 (Jun 2017) ISSN: 1420-908X [Electronic] Switzerland
• PMID: 28289752 (Publication Type: Journal Article)

Chemical References

• 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

Topics

• Animals
• Anti-Inflammatory Agents (chemistry, pharmacology)
• Inflammation (metabolism)
• Interleukin-1beta (metabolism)
• Isothiocyanates (chemistry, 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, pharmacology)
• p38 Mitogen-Activated Protein Kinases (antagonists & inhibitors)