Anti-apoptotic and anti-inflammatory properties of grapefruit IntegroPectin on human microglial HMC3 cell line
Miriana ScordinoiD, Giulia UroneiD, Monica FrinchiiD, Chiara ValenzaiD, Angela BonuraiD, Chiara CipollinaiD, Rosaria CiriminnaiD, Francesco MeneguzzoiD, Mario PagliaroiD, Giuseppa MudòiD, Valentina Di LibertoiD
Abstract
Background and aim O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=127 SRC="FIGDIR/small/549931v1_ufig1.gif" ALT="Figure 1"> View larger version (29K): org.highwire.dtl.DTLVardef@2a9626org.highwire.dtl.DTLVardef@1e7a321org.highwire.dtl.DTLVardef@870907org.highwire.dtl.DTLVardef@161aef0_HPS_FORMAT_FIGEXP M_FIG C_FIG Despite the intense research, most therapeutic strategies failed in preventing or treating neurodegenerative diseases, characterized by a combination of chronic neurodegeneration, oxidative stress and neuroinflammation. The broad protective activity of IntegroPectin derived from industrial waste grapefruit peel via hydrodynamic cavitation has been recently characterized. In this study, we investigated the beneficial effects of grapefruit IntegroPectin treatment in microglia cells exposed to oxidative stress conditions. Experimental procedureHuman microglial HMC3 cells were challenged with tert-butyl hydroperoxide (TBH), a powerful hydroperoxide, in the presence of grapefruit IntegroPectin. The apoptotic process, the oxidative stress and the neuroinflammatory responses with the relative intracellular cascades were evaluated. Key resultsGrapefruit IntegroPectin fully counteracted the apoptotic process induced by cell exposure to TBH. The protective effects of grapefruit IntegroPectin were accompanied with a decrease in the amount of ROS, and were strictly dependent on the activation of the PI3K/Akt cascade. Finally, IntegroPectin treatment inhibited basal microglia activation and the neuroinflammatory response by down-regulating the PI3K-NF-kB-iNOS cascade. Conclusions and implicationsThese findings reveal that the innovative IntegroPectin exerts a potent protective activity on microglia cells and strongly support further investigations aimed at exploring its therapeutic role in in vivo models of neurodegenerative disorders.
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