Abstract
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 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.
Conclusion:
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.
Similar content being viewed by others
Log in or create a free account to read this content
Gain free access to this article, as well as selected content from this journal and more on nature.com
or
References
Wimo A, Winblad B, Jonsson L . The worldwide societal costs of dementia: Estimates for 2009. Alzheimers Dement 2010; 6: 98–103.
Sloane PD, Zimmerman S, Suchindran C, Reed P, Wang L, Boustani M, et al. The public health impact of Alzheimer's disease, 2000–2050: potential implication of treatment advances. Annu Rev Public Health 2002; 23: 213–31.
Cras P, Kawai M, Lowery D, Gonzalez DP, Greenberg B, Perry G . Senile plaque neurites in Alzheimer disease accumulate amyloid precursor peptide. Proc Natl Acad Sci U S A 1991; 88: 7552–6.
Blanquet V, Goldgaber D, Turleau C, Creau GN, Delabar J, Sinet PM, et al. The beta amyloid peptide (AD–AP) cDNA hybridizes in normal and Alzheimer individuals near the interface of 21q21 and q22.1. Ann Genet 1987; 30: 68–9.
Ove A . The bittersweet promise of glycobiology. Nat Biotechnol 2001; 19: 913–7.
Sasaki T, Takasuka N . Further study of the structure of lentinan, an anti-tumor polysaccharide from Lentinus edodes. Carbohydr Res 1976; 47: 99–104.
Schaefer DJ, Krylov VS . Anti-HIV activity of extracts and compounds from algae and cyanobacteria. Ecotoxicol Environ Saf 2000; 45: 208–27.
Kim HM, Kang JS, Kim JY . Evaluation of antidiabetic activity of polysaccharide isolated from Phellinus linteus in non-obese diabetic mouse. Int Immunopharmacol 2010; 10: 72–8.
Ho YS, Yu MS, Yang XF, So KF, Yuen WH, Chang RC . Neuroprotective effects of polysaccharides from wolfberry, the fruits of Lycium barbarum, against homocysteine-induced toxicity in rat cortical neurons. J Alzhiermers Dis 2010; 19: 813–27.
Townsend M, Cleary JP, Mehta T, Hofmeister J, Lesne S, Selkoe DJ, et al. Orally available compound prevents deficits in memory caused by the Alzheimer amyloid-β oligomers. Ann Neurol 2006; 60: 668–76.
Geng MY . Protective effect of marine-derived oligosaccharide as a candidate anti-AD drug and its related mechanisms. Chin Pharmacologist 2007; 24: 7.
Geng MY, Xin XL, Sun GQ . Preparation of brown algae oligosaccharide and its derivatives and their uses. CN 200580009396.5.
Crich D, Sun SX . Formation of beta-mannopyranosides of primary alcohols using the sulfoxide method. J Org Chem 1996; 61: 4506–7.
Crich D, Sun SX . Direct synthesis of beta-mannopyranosides by the sulfoxide method. J Org Chem 1997; 62: 1198–9.
Crich D, Mataka J, Sun SX, Lam KC, Rheingold AL, Wink DJ . Stereoselective sulfoxidation of alpha-mannopyranosyl thioglycosides: The exo-anomeric effect in action. Chem Commun 1998; 24: 2763–4.
Crich D, Mark S, Yao QJ, John P . 2,4,6-Tri-tert-butylpyrimidine (TTBP): A cost effective, readily available alternative to the hindered base 2,6-di-tert-butylpyridine and its 4-substituted derivatives in glycosylation and other reactions. Synth Stuttgart 2000; 2: 323–6.
Crich D, Li WJ, Li HM . Direct chemical synthesis of the beta-mannans: Linear and block syntheses of the alternating beta-(l→3)-beta-(l→4)-mannan common to Rhodotorula glutinis, Rhodotorula mucilaginosa, and Leptospira biflexa. J Am Chem Soc 2004; 126: 15081–6.
Crich D, Sun SX . Direct chemical synthesis of beta-mannopyranosides and other glycosides via glycosyl triflates. Tetrahedron 1998; 54: 8321–48.
Jalsa NK, Singh G . A unique approach to the synthesis of a dengue vaccine and the novel tetrasaccharide that results. Tetrahedron-Asymmetry 2009; 20: 867–74.
Bock K, Pedersen C . A study of 13CH coupling constants in hexopyranoses. J Chem Soc Perkin Trans 2 1974; 3: 293–7.
Ikeda R, Maeda T . Structural studies of the capsular polysaccharide of a non-neoformans Cryptococcus species identified as C-laurentii, which was reclassified as Cryptococcus flavescens, from a patient with AIDS. Carbohydr Res 2004; 339: 503–9.
Chow JT, Williamson DA, Yates KM, Goux WJ . Chemical characterization of the immunomodulating polysaccharide of Aloe vera L. Carbohydr Res 2005; 340: 1131–42.
Issa MA . Structural investigation of water-hyacinth (Eichhornia-Crassipes) polysaccharides. 1. Water-Soluble Polysaccharides. Can J Chem 1988; 66: 2777–81.
Fujimoto H, Isomura M, Ajisaka K . Syntheses of alkyl beta-D-mannopyranosides and beta-1,4-linked oligosaccharides using beta-mannosidase from Rhizopus niveus. Biosci Biotech Bioch 1997; 61: 164–5.
Acknowledgements
This work was supported by the National Science & Technology Major Project “Key New Drug Creation and Manufacturing Program,” China (2012ZX09301001).
Author information
Authors and Affiliations
Corresponding authors
Rights and permissions
About this article
Cite this article
Jiang, Rw., Du, Xg., Zhang, X. et al. Synthesis and bioassay of β-(1,4)-D-mannans as potential agents against Alzheimer's disease. Acta Pharmacol Sin 34, 1585–1591 (2013). https://doi.org/10.1038/aps.2013.104
Received:
Accepted:
Published:
Issue date:
DOI: https://doi.org/10.1038/aps.2013.104
Keywords
This article is cited by
-
A 36-week multicenter, randomized, double-blind, placebo-controlled, parallel-group, phase 3 clinical trial of sodium oligomannate for mild-to-moderate Alzheimer’s dementia
Alzheimer's Research & Therapy (2021)
-
Omission of previous publications by an author should be corrected
Cell Research (2020)
-
Characterization of lactic acid bacteria derived exopolysaccharides for use as a defined neuroprotective agent against amyloid beta1–42-induced apoptosis in SH-SY5Y cells
Scientific Reports (2020)
-
Sodium Oligomannate: First Approval
Drugs (2020)
-
A phase II randomized trial of sodium oligomannate in Alzheimer’s dementia
Alzheimer's Research & Therapy (2020)
