Investigation Of The Anti-inflammatory Activity And Molecular Mechanism Of Alginate-derived Oligosaccharides

Inflammation is a common and important pathological process. Increasing evidences confirmed that inflammation is associated with various diseases, such as cancer, obesity, cardiovascular diseases and Alzheimer’s disease. Hence, the study of anti-inflammatory is crucial to develop new nutraceuticals or drugs for treatment inflammatory-mediated diseases. In vivo, activated macrophages can produce a large number of inflammatory mediators that induced inflammatory response and resulted inflammation diseases.Alginates are naturally polysaccharide found in brown seaweed, and are copolymerized alternatively by the two monomers, α-1,4-L-guluronic(G) and β-1,4-D-mannuronic(M). Firstly, polyguluronate(PG) and polymannuronate(PM) were prepared from alginate, and alginate-derived oligosaccharides(Ad O) were prepared by oxidative degradation(OD). The purity, chemical structures and degree of polymerization(DP) of polysaccharides and oligosaccharides were analyzed by the infrared(IR) spectrum, circular dichroic(CD) spectrum and thin-layer chromatography(TLC).In this study, we found that alginate oligosaccharides prepared by oxidative degradation(Ad O) significantly attenuated the production of NO, PGE2 and ROS, the expression of inducible i NOS and COX-2, and the secretion of pro-inflammatory cytokines in LPS-activated murine RAW 264.7 cells. Furthermore, Ad O potently decreased the expression of LPS-induced toll-like receptor 4(TLR4) and cluster of differentiation(CD) 14. Finally, we found that Ad O remarkably inhibited LPS-induced activation of nuclear factor(NF)-κB and mitogen-activated protein(MAP) kinases pathways in RAW 264.7 cells. These results indicate that Ad O may reduce the inflammatory responses stimulated by LPS through inhibiting the activation of NF-κB and MAP kinases by expression of TLR4 and CD14 in RAW 264.7 cells.Moreover, neuroinflammation is one of the causes of neurodegenerative diseases, are important predisposing factors. Inhibition of the inflammation in the brain is beneficial for prevention and treatment of neurodegenerative diseases. In this study, we found that Ad O significantly attenuated the production of NO, PGE2, the expression of i NOS and COX-2, and the secretion of pro-inflammatory cytokines in LPS-activated murine BV2 cells. Furthermore, we found that Ad O significantly attenuated the production of the secretion of pro-inflammatory cytokines in Aβ-activated murine BV2 cells. Ad O potently decreased the expression of LPS-induced TLR4. Finally, we found that Ad O remarkably inhibited LPS-induced activation of NF-κB in BV2 cells. These results indicate that Ad O may reduce the inflammatory responses stimulated by LPS through inhibiting the activation of NF-κB by inhibiting the expression of TLR4 in BV2 cells.