Monovalent glycoconjugates of sulforaphane prevent inflammation induced by lipopolysaccharide in human dendritic cells by inhibiting NF‐ĸB signalling pathway

Background and Purpose Sulforaphane (SFN) has notable health benefits but faces challenges due to its poor solubility and delivery. This study investigates SFN‐glycoconjugates effects on lipopolysaccharide (LPS)‐induced inflammation in dendritic cells (DCs). With the aiming to enhance their therapeutic potential against inflammatory diseases. Novel monovalent SFN‐glycoconjugates with mannose (Man) and fucose (0Fuc) were developed and tested for their anti‐inflammatory and immune‐modulatory properties in DCs from healthy donors under chronic LPS exposure. Experimental Approach By leveraging therapeutic strategies, SFN‐glycoconjugates significantly improved the solubility and bioavailability of SFN, thereby overcoming the limitations of traditional delivery methods. Monocyte‐derived DCs were treated with SFN‐glycoconjugates and subsequently exposed to a chronic inflammatory environment induced by LPS. Key Results Our results showed that SFN‐glycoconjugates enhance effectiveness in suppressing inflammation by targeting the p65 NF‐κB pathway, without affecting MAPK signalling. SFN‐glycoconjugates induce a tolerogenic immune response, characterized by increased IL‐10 production and enhanced regulatory T‐ and B‐cell proliferation. These effects surpass those of p65 NF‐κB inhibition alone, highlighting a distinct and potent regulatory mechanism independent of MAPK pathways. Conclusion and Implications The integration of food therapeutic strategies not only enhances the stability and delivery of bioactive compounds but also broadens their potential applications in functional foods and therapeutic approaches. In particular, SFN‐glycoconjugates represent a promising option as biologically active compounds for inflammatory diseases, offering enhanced anti‐inflammatory and immunomodulatory effects through optimized delivery systems and the activation of specific molecular pathways.