Inhibitory action of salicylideneamino-2-thiophenol on NF-κB signaling cascade and cyclooxygenase-2 in HNE-treated endothelial cells

Abstract

In the present study, the anti-inflammatory effect of salicylideneamino-2-thiophenol (SAL-2), a derivative of salicylate, on a potent oxidant 4-hydroxynonenal (HNE)-induced oxidative stress was investigated using rat prostate endothelial (YPEN-1) cells. We focused on anti-inflammatory activity of SAL-2 which was determined by its ability to suppress COX-2 and iNOS gene expression through suppression of NF-κB and redox regulation. We found that SAL-2 effectively inhibited HNE-induced reactive species generation, while upregulated GSH/GSSG ratio. Prostagrandin (PG) E2 production stimulated by arachidonic acid was suppressed by SAL-2. SAL-2 also downregulated COX-2 and iNOS expression induced by HNE, but salicylate did not. We found that SAL-2 inhibited HNE-mediated IKK phosphorylation, IκBα degradation and nuclear translocation of p65 which are linked to NF-κB activation. Furthermore, SAL-2 inhibited HNE-induced activation of mitogen-activated protein kinases. Collectively, SAL-2 inhibited COX-2 and iNOS gene expression through suppression of NF-κB leading to the inhibition of PGE2 synthesis. Based on these data, we propose that with its combined effect on strong anti-oxidant and anti-inflammatory action, SAL-2 can be a potent anti-inflammatory agent for treatment of inflammatory-related diseases.

4-hydroxynonenal-mediated signaling and aging

“…Conjugation and inhibition of either IKKα [53] or IKKβ [55] was reported. However, there was controversial report that at high concentration (15 μM) HNE increased IKK phosphorylation and activation, and IkBα degradation, and thus increased NF-κB activation in rat prostate endothelial cells [60]. In summary, the ability of HNE to activate NF-κB signaling at concentration as low as that found in the plasma of elderly suggests a potential role of HNE in the age-related increase of NF-κB activity and proinflammatory cytokines.…”

Salicylideneamino‐2‐thiophenol modulates nuclear factor‐κB through redox regulation during the aging process

“…It is known that at concentrations higher than 5 mmol/L, salicylate inhibits many cellular kinases nonspecifically. 36 However, studies by our collaborator and the present authors showed SAL-2 at pharmacological concentrations inhibits NF-κB activation 15,16 and COX-2 activity more than sodium salicylate. 16 Jung et al showed that short-term, low-dose aspirin supplementation reduces oxidative stress and the activation of pro-inflammatory NF-κB in aged rat kidneys.…”

“…1) has been reported to modulate oxidative stress-induced dysregulation of redox-status and pro-inflammatory gene expressions in rat peritoneal macrophages and rat prostate endothelial (YPEN-1) cells. 15,16 In multipotent bone marrow stem cells, SAL-2 has been shown to enhance osteogenic differentiation through the activation of mitogen-activated protein kinases pathways. 17 However, the effects of SAL-2 on anti-inflammatory properties have not been studied in aged rats.…”

Modulatory effects of thymol and carvacrol on inflammatory transcription factors in lipopolysaccharide-treated macrophages

“…Salicylates and glucocorticoids are two commonly used anti-inflammatory drugs that have inhibitory effects on NF-jB activation (de Bosscher et al, 2014;Park et al, 2013). Other non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen and flurbiprofen act similarly (D'Acquisto et al, 2002).…”