Immunomodulatory\nEffects and Regulatory Mechanisms\nof (<i>R</i>)‑6-HITC, an Isothiocyanate from Wasabi\n(Eutrema japonicum), in an <i>Ex Vivo</i> Mouse Model of LPS-Induced Inflammation

The present study aimed to investigate the effects of\n(<i>R</i>)-(−)-1-isothiocyanato-6-(methylsulfinyl)-hexane\n[(<i>R</i>)-6-HITC], the major isothiocyanate present in\nwasabi, in an <i>ex vivo</i> model of inflammation using\nlipopolysaccharide-stimulated murine peritoneal macrophages. (<i>R</i>)-6-HITC improved the immune response and mitigated oxidative\nstress, which involved suppression of reactive oxygen species, nitric\noxide, and pro-inflammatory cytokines (IL-1β, IL-6, IL-17, IL-18,\nand TNF-α) production and downregulation of pro-inflammatory\nenzymes such as inducible nitric oxide synthase, COX-2, and mPGES-1.\nIn addition, (<i>R</i>)-6-HITC was able to activate the\nNrf2/HO-1 axis while simultaneously inhibiting key signaling pathways,\nincluding JAK2/STAT3, mitogen-activated protein kinases, and canonical\nand noncanonical inflammasome pathways, orchestrating its potent immunomodulatory\neffects. Collectively, these findings demonstrate the potential of\n(<i>R</i>)-6-HITC as a promising nutraceutical for the management\nof immuno-inflammatory diseases and justify the need for further <i>in vivo</i> validation studies.