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Purpose: Sulfated galactofucan (SWZ-4), which was extracted from Sargassum thunbergii, has recently been reported to have anti-inflammatory and anti-cancer property. The present study aimed to evaluate if SWZ-4 could attenuate atherosclerosis in Apolipoprotein E-deficient (ApoE KO) mice by suppressing inflammatory response through TLR4/MyD88/NF-κB signaling pathway.Methods: Male ApoE KO mice were fed with high-fat diet for 16 weeks and intraperitoneally injected with SWZ-4. RAW246.7 cells were treated with lipopolysaccharide (LPS) and SWZ-4. Atherosclerotic lesions were measured by Sudan IV and Oil Red O staining. Serum lipid profiles, inflammatory cytokines, and mRNA and protein expression levels were evaluated.Results: SWZ-4 decreased serum TNF-α, IL-6 and IL-1 levels, but cannot improve blood lipid profiles. SWZ-4 downregulated the mRNA and protein expression of TLR4, MyD88 and phosphorylation of p65 and attenuated atherosclerosis in the ApoE KO mice (P < 0.01). In LPS-stimulated RAW 264.7 cells, SWZ-4 inhibited pro-inflammatory cytokines and the mRNA expression of TLR4, MyD88 and p65 and reduced the proteins expression of TLR4, MyD88 and the phosphorylation of p65 (P < 0.01).Conclusion: These results suggest that SWZ-4 exerts an anti-inflammatory effect in ApoE KO atherosclerosis mice via inhibiting TLR4/MyD88/NF-κB signaling pathway in macrophages, and may potentially serve as a treatment for atherosclerosis. |
