Immunomodulatory Effects and Regulatory Mechanisms of ( R )-6-HITC, an Isothiocyanate from Wasabi ( Eutrema japonicum ), in an Ex Vivo Mouse Model of LPS-Induced Inflammation.
Manuel AlcarranzaCatalina Alarcón-de-la-LastraRocío Recio JiménezInmaculada FernándezMaría Luisa Castejón MartínezIsabel VillegasPublished in: Journal of agricultural and food chemistry (2024)
The present study aimed to investigate the effects of ( R )-(-)-1-isothiocyanato-6-(methylsulfinyl)-hexane [( R )-6-HITC], the major isothiocyanate present in wasabi, in an ex vivo model of inflammation using lipopolysaccharide-stimulated murine peritoneal macrophages. ( R )-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, ( R )-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 ( R )-6-HITC as a promising nutraceutical for the management of immuno-inflammatory diseases and justify the need for further in vivo validation studies.
Keyphrases
- oxidative stress
- lps induced
- nitric oxide
- nitric oxide synthase
- signaling pathway
- inflammatory response
- immune response
- mouse model
- reactive oxygen species
- induced apoptosis
- dna damage
- diabetic rats
- ischemia reperfusion injury
- rheumatoid arthritis
- anti inflammatory
- toll like receptor
- cell proliferation
- epithelial mesenchymal transition
- risk assessment
- hydrogen peroxide
- climate change
- heat stress
- heat shock protein