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 H2O2. 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.
Highlights
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
In this paper we investigated the effect of three ITCs i.e. Allyl isothiocyanate (AITC), 2-Phenethyl isothiocyanate (PEITC) and 2-Sulforaphane (SFN) on the release of matrix metalloproteinase (MMP)-2 and -9 as well as on reactive oxygen species (ROS) production by LPS-activated astrocytes
Protective effect of ITC compounds on ROS production in hydrogen peroxide‐treated astrocytes
Summary
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. In the CNS, MMPs are involved in various physiological responses, such as morphogenesis, turnover and remodelling of ECM, embryogenesis and wound repair; 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 disorders (Latronico and Liuzzi 2017; Mastroianni and Liuzzi 2007; Brkic et al 2015). Experimental evidence has suggested that among MMPs, gelatinases A (MMP-2) and B (MMP-9) are involved in neuroinflammation since their upregulation may compromise the integrity of blood brain barrier (BBB) This leads to increased recruitment and infiltration of immune peripheral blood cells into the brain parenchyma perpetuating the inflammatory process that is cause of progressive neuronal loss and impaired neuronal function (Rivest 2009). Several in vitro and in vivo studies have shown ROS production is one of the factors involved in the up-regulation of MMP-9 expression in brain cells via mitogen activated protein kinase (MAPK) signaling pathway dependent mechanisms (Hsieh and Yang 2013)
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