Synthesis and bioassay of β-(1,4)-D-mannans as potential agents against Alzheimer's disease.
OBJECTIVE
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 Aβ peptide toxicity in vitro.


METHODS
The sulfoxide method was applied to synthesize the derivatives. SH-SY5Y human neuroblastoma cells were treated with Aβ1-40 (2 μmol/L), and the cell viability was detected using a CCK8 assay.


RESULTS
A series of β-(1,4)-D-mannosyl oligosaccharide, ranging from the disaccharide to the hexasaccharide, were synthesized. Addition of 10 μmol/L β-(1,4)-D-mannobiose 6, β-(1,4)-D-mannotriose 9 or β-(1,4)-D-mannotetraose 12 in SH-SY5Y cells significantly attenuated Aβ1-40-induced toxicity. The efficacies were similar to those caused by 10 μmol/L oligomannurarate 971 or alzhemed. Other oligosaccharides including oligomaltoses and oligocelluloses were less active.


CONCLUSIONS
Synthetic homogeneous short chain β-(1,4)-D-mannans shows neuroprotective effect against Aβ peptide toxicity similar to that of heterogeneous oligomannurarate 971 and alzhemed.
State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Shanghai 201203, China.
Ru-wei
RW
Jiang
Xiao-guang
XG
Du
Xuan
X
Zhang
Xin
X
Wang
Ding-yu
DY
Hu
Tao
T
Meng
Yue-lei
YL
Chen
Mei-yu
MY
Geng
Jing-kang
JK
Shen
D000544:Alzheimer Disease / Q000188:drug therapy*; D001681:Biological Assay; D002240:Carbohydrate Sequence; D006801:Humans; D008351:Mannans / Q000737:chemistry / Q000627:therapeutic use*; D008969:Molecular Sequence Data; D018696:Neuroprotective Agents / Q000737:chemistry / Q000627:therapeutic use*
D008351:Mannans; D018696:Neuroprotective Agents