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

The present study aimed to investigate the effects of (<i>R</i>)-(-)-1-isothiocyanato-6-(methylsulfinyl)-hexane [(<i>R</i>)-6-HITC], the major isothiocyanate present in wasabi, in an <i>ex vivo</i> model of inflammation using lipopolysaccharide-stimulated murine peritoneal macrophages. (<i>R</i>)-6-HITC improved the immune response and mitigated oxidative stress, which involved suppression of reactive oxygen species, nitric oxide, and pro-inflammatory cytokines (IL-1β, IL-6, IL-17, IL-18, and TNF-α) production and downregulation of pro-inflammatory enzymes such as inducible nitric oxide synthase, COX-2, and mPGES-1. In addition, (<i>R</i>)-6-HITC was able to activate the Nrf2/HO-1 axis while simultaneously inhibiting key signaling pathways, including JAK2/STAT3, mitogen-activated protein kinases, and canonical and noncanonical inflammasome pathways, orchestrating its potent immunomodulatory effects. Collectively, these findings demonstrate the potential of (<i>R</i>)-6-HITC as a promising nutraceutical for the management of immuno-inflammatory diseases and justify the need for further <i>in vivo</i> validation studies.