Covalent Modification of Selenium in Polysaccharide Enhances Immunoregulation Activity via the TLR4-Mediated...

Area of Science:

• Immunology
• Biochemistry
• Materials Science

Background:

• Selenium (Se) is a vital trace element with potent immunomodulatory properties, influenced by its diverse valence states and metabolic pathways.
• Locust bean gum (LBG), a galactomannan, serves as a functional polysaccharide carrier for selenium modification.

Purpose of the Study:

• To synthesize and characterize selenium-covalent modified locust bean gum (SeLBG) using deep eutectic solvents (DESs).
• To evaluate the immunomodulatory effects of SeLBG compared to LBG and various selenium compounds.
• To elucidate the underlying molecular mechanisms, including signaling pathways and receptor interactions.

Main Methods:

• Selenization of LBG using DESs to produce SeLBGs with varying selenium content.
• Assessment of immunomodulatory activity through cell viability, phagocytosis, cytokine secretion, and protein expression assays.
• Molecular docking, molecular dynamics simulations, and receptor inhibitor strategies to investigate TLR activation.

Main Results:

• SeLBGs exhibited superior immunomodulatory activities compared to native LBG and selenium compounds (Se-Met, Na2SeO3, SeNPs) at equivalent selenium concentrations.
• SeLBG activated MAPKs and NF-κB signaling pathways, leading to enhanced cell viability, phagocytic activity, and cytokine secretion.
• Molecular simulations indicated SeLBG's potential to induce toll-like receptor (TLR) dimerization and activation, confirmed by inhibitor studies showing enhanced TLR2/4 recognition.

Conclusions:

• Selenium-covalent modified locust bean gum (SeLBG) possesses enhanced immunomodulatory capabilities.
• The observed effects are mediated through the activation of MAPKs, NF-κB, and TLR2/4 signaling pathways.
• SeLBG represents a promising functional ingredient with potential applications in immune health and related fields.