This study elucidates the regulatory mechanism of Alhagi honey polysaccharide on Toll-like receptor 4 (TLR4).An immunosuppressive mouse model was established using C57BL/6J mice,and a RAW 264.7 model induced by TAK-242 inhibitor was constructed.In the mouse model,Alhagi honey polysaccharide were administered at 800 mg/kg,while the RAW 264.7 model received interventions with different concentrations of Alhagi honey polysaccharide (25,50,75,100 μg/mL).Enzyme-linked immunosorbent assay (ELISA) was employed to measure cytokine levels in mouse serum and RAW 264.7 cell culture supernatant.Protein immunoblotting and real-time quantitative PCR (qRT-PCR) were conducted to detect the expression of TLR4,myeloid differentiation factor 88 (MyD88),and tumor necrosis factor-α receptor associated factor 6 (TRAF6) in relevant tissues and cells.Results indicate that Alhagi honey polysaccharide significantly increased the spleen index,thymus index,and serum levels of interleukin-2 (IL-2),interleukin-4 (IL-4),tumor necrosis factor-α (TNF-α),immunoglobulin G (IgG),and immunoglobulin M (IgM) in immunosuppressive mice.In the TAK-242 inhibitor-induced cell model,Alhagi honey polysaccharide increased the secretion of interleukin-1β (IL-1β),interleukin-6 (IL-6),interleukin-12 (IL-12),TNF-α,and nuclear factor-κB (NF-κB).Furthermore,Alhagi honey polysaccharide reversed the downregulation of TLR4 and MyD88/TRAF6 expression.Alhagi honey polysaccharide can activate the immune response of TLR4 receptors by modulating the MyD88 pathway.