Synthesis and bioassay of β-(1,4)-D-mannans as potential agents against Alzheimer's disease

Aim: Oligomannurarate 971 derived from a marine plant has shown neuroprotective effects. In this study we synthesized a series of truncated derivatives of the oligosaccharide, and investigated the effect of these derivatives against A beta peptide toxicity in vitro. Methods: The sulfoxide method was applied to synthesize the derivatives. SH-SY5Y human neuroblastoma cells were treated with A beta(1-40) (2 mu mol/L), and the cell viability was detected using a CCK8 assay. Results: A series of beta-(1,4)-D-mannosyl oligosaccharide, ranging from the disaccharide to the hexasaccharide, were synthesized. Addition of 10 mu mol/L beta-(1,4)-D-mannobiose 6, beta-(1,4)-D-mannotriose 9 or beta-(1,4)-D-mannotetraose 12 in SH-SY5Y cells significantly attenuated A beta 1-40-induced toxicity. The efficacies were similar to those caused by 10 mu mol/L oligomannurarate 971 or alzhemed. Other oligosaccharides including oligomaltoses and oligocelluloses were less active. Conclusion: Synthetic homogeneous short chain beta-(1,4)-D-mannans shows neuroprotective effect against A beta peptide toxicity similar to that of heterogeneous oligomannurarate 971 and alzhemed.