Neuroprotective potential of isothiocyanates in an in vitro model of neuroinflammation
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Inflammopharmacology
ORIGINAL ARTICLE
Neuroprotective potential of isothiocyanates in an in vitro model of neuroinflammation Tiziana Latronico1 · Marilena Larocca2 · Serafina Milella1 · Anna Fasano1 · Rocco Rossano2 · Grazia Maria Liuzzi1 Received: 10 July 2020 / Accepted: 25 October 2020 © The Author(s) 2020
Abstract Isothiocyanates (ITCs), present as glucosinolate precursors in cruciferous vegetables, have shown anti-inflammatory, antioxidant and anticarcinogenic activities. Here, we compared the effects of three different ITCs on ROS production and on the expression of matrix metalloproteinase (MMP)-2 and -9, which represent important pathogenetic factors of various neurological diseases. Primary cultures of rat astrocytes were activated by LPS and simultaneously treated with different doses of Allyl isothiocyanate (AITC), 2-Phenethyl isothiocyanate (PEITC) and 2-Sulforaphane (SFN). Results showed that SFN and PEITC were able to counteract ROS production induced by H 2O2. The zymographic analysis of cell culture supernatants evidenced that PEITC and SFN were the most effective inhibitors of MMP-9, whereas, only SFN significantly inhibited MMP-2 activity. PCR analysis showed that all the ITCs used significantly inhibited both MMP-2 and MMP-9 expression. The investigation on the mitogen-activated protein kinase (MAPK) signaling pathway demonstrated that ITCs modulate MMP transcription by inhibition of extracellular-regulated protein kinase (ERK) activity. Results of this study suggest that ITCs could be promising nutraceutical agents for the prevention and complementary treatment of neurological diseases associated with MMP involvement. Keywords Antioxidant · Anti-inflammatory · Isothiocyanate · Matrix metalloproteinases · Neurodegenerative diseases
Introduction Neuroinflammation is a complex response to brain injury involving a cascade of biochemical events leading to the activation of central nervous system (CNS) resident cells. The aberrant activation of astrocytes compromises their neuroprotective role leading to release of inflammatory mediators, such as reactive oxygen species (ROS), nitric oxide (NO), cytokines, chemokines and matrix metalloproteinases (MMPs). MMPs are a large family of neutral, Zn2+-dependent endopeptidases that have as major targets the components of the extracellular matrix (ECM) such as fibronectin, collagen, elastin and laminin (Latronico and Liuzzi 2017). * Tiziana Latronico [email protected] 1
Department of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari “Aldo Moro”, Bari, Italy
Department of Sciences, University of Basilicata, Potenza, Italy
2
In the CNS, MMPs are involved in various physiological responses, such as morphogenesis, turnover and remodelling of ECM, embryogenesis and wound repair; however, when MMPs escape regulatory mechanisms they become harmful (Rosenberg 2009; Agrawal et al. 2008). In this respect, it is known that alterations in MMP expression and activity are key pathogenetic events in several neurological disord
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