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

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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.

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Acknowledgements

This study was supported by the current research funds 2016 of IRCCS “Centro Neurolesi Bonino-Pulejo”, Messina, Italy.

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    Authors and Affiliations

    1. IRCCS Centro Neurolesi “Bonino-Pulejo”, Via Provinciale Palermo, Contrada Casazza, 98124, Messina, Italy

      Sabrina Giacoppo, Thangavelu Soundara Rajan, Placido Bramanti & Emanuela Mazzon

    2. 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

      Renato Iori

    3. Université d’Orléans et CNRS, ICOA, UMR 7311, BP 6759, 45067, Orléans, France

      Patrick Rollin

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    1. Sabrina Giacoppo
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    Responsible Editor: John Di Battista.

    S. Giacoppo and T. S. Rajan have contributed equally.

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    Giacoppo, S., Rajan, T.S., Iori, R. et al. 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. 66, 487–503 (2017). https://doi.org/10.1007/s00011-017-1033-7

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