Covalent Modification of Selenium in Polysaccharide Enhances Immunoregulation Activity via the TLR4-Mediated MAPK/NF-κB Signaling Pathway

Selenium (Se) is a crucial trace element that demonstrates significant immunomodulatory effects, which are attributed to the variability in its valence states and metabolic pathways. To investigate the Se-related immunoregulatory effects, locust bean gum (LBG), a typical galactomannan, was selenized by employing deep eutectic solvents (DESs) as high-efficiency solvents to obtain Se-covalent modified LBG (SeLBGs) with similar molecular mass and different Se contents (SeLBG_L, 1049.57 and SeLBG_H, 4926.54 μg/g). After introducing selenite into LBG, SeLBGs display greater immunomodulatory activities by activating MAPKs and NF-κB signaling pathways compared with LBG and Se compounds (Se-Met, Na₂SeO₃, and SeNPs) at the same Se equivalent, which are confirmed by their higher cell viability, phagocytic activity, secretion of cytokines, and protein expression. In addition, molecular docking and molecular dynamics suggest that SeLBG has the potential to induce dimerization of subunits and activate toll-like receptors (TLRs). By employing the specific receptor inhibitors strategy, it is confirmed that the combination of Se and LBG enhances TLR2/4 recognition according to the results of cytokine secretion and MAPKs/NF-κB pathway-related protein expression. These findings underscore the role of Se in pattern receptor recognition and the potential of Se-enriched ingredients in various functions.