Inhibitory effects of sulforaphane on Polyphosphate-Mediated septic responses

Background and Objective: Sulforaphane (SFN), a natural isothiocyanate present in cruciferous vegetables, such as broccoli and cabbage, is effective in preventing carcinogenesis, diabetes and inflammatory responses. Human endothelial cell-derived polyphosphate (PolyP) is a proinflammatory mediator. This study was undertaken to investigate whether SFN can modulate PolyP-mediated inflammatory responses in Human Umbilical Vein Endothelial Cells (HUVECs) and mice. Materials and Methods: The anti-inflammatory activities of SFN were determined by measuring the permeability, leukocyte adhesion and migration and activation of proinflammatory proteins in PolyP-activated HUVECs and mice. In addition was determined the beneficial effects of SFN on survival rate in PolyP-injected mice. Statistical relevance was determined by one-way analysis of variance (ANOVA) and Tukey’s post-test. Results: Data showed that SFN inhibits PolyP-mediated barrier disruption, cell adhesion molecule expression and leukocyte to HUVEC adhesion/migration. Notably, PolyP-induced NF-κB activation and TNF-α and IL-6 production were inhibited by SFN in HUVECs. These anti-inflammatory functions of SFN were confirmed in PolyP injected mice. Conclusion: Based on the anti-inflammatory effects of SFN in PolyP-mediated septic response, SFN could be considered a potential agent for the treatment of sepsis and other diseases in which PolyP is viewed as a therapeutic target.