title: 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.affiliation: IRCCS Centro Neurolesi "Bonino-Pulejo", Via Provinciale Palermo, Contrada Casazza, 98124, Messina, Italy.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Giacoppo
authors.affiliation: IRCCS Centro Neurolesi "Bonino-Pulejo", Via Provinciale Palermo, Contrada Casazza, 98124, Messina, Italy.
authors.forename: Thangavelu Soundara
authors.initials: TS
authors.lastname: Rajan
authors.affiliation: Consiglio per la ricerca in agricoltura e l'analisi dell'economia agraria, Centro di ricerca Agricoltura e Ambiente (CREA-AA), Via di Corticella 133, 40128, Bologna, Italy.
authors.forename: Renato
authors.initials: R
authors.lastname: Iori
authors.affiliation: Université d'Orléans et CNRS, ICOA, UMR 7311, BP 6759, 45067, Orléans, France.
authors.forename: Patrick
authors.initials: P
authors.lastname: Rollin
authors.affiliation: IRCCS Centro Neurolesi "Bonino-Pulejo", Via Provinciale Palermo, Contrada Casazza, 98124, Messina, Italy.
authors.forename: Placido
authors.initials: P
authors.lastname: Bramanti
authors.affiliation: IRCCS Centro Neurolesi "Bonino-Pulejo", Via Provinciale Palermo, Contrada Casazza, 98124, Messina, Italy. emazzon.irccs@gmail.com.
authors.forename: Emanuela
authors.initials: E
authors.lastname: Mazzon
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000494:pharmacology*; D007249:Inflammation / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D017879:Isothiocyanates / Q000737:chemistry / Q000494:pharmacology*; D008070:Lipopolysaccharides; D051379:Mice; D029587:Moringa; D000072000:NF-KappaB Inhibitor alpha / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors; D000067996:RAW 264.7 Cells; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D047391:alpha-Cyclodextrins / Q000737:chemistry / Q000494:pharmacology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors
chemical_list: D000893:Anti-Inflammatory Agents; C587672:IL1B protein, mouse; D053583:Interleukin-1beta; D017879:Isothiocyanates; D008070:Lipopolysaccharides; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D047391:alpha-Cyclodextrins; C000614007:moringin; D000072000:NF-KappaB Inhibitor alpha; D051057:Proto-Oncogene Proteins c-akt; D048051:p38 Mitogen-Activated Protein Kinases; C032613:alpha-cyclodextrin
keywords: Akt; Inflammation; Moringa isothiocyanate; P38; RAW 264.7 macrophage cells; α-CD-complexed moringin