Table 4.
Saccharides and saccharide-rich extracts exert neuroprotective effects in vitro and in vivo
| Polysaccharide(s) | Source(s) | Neuronal preparation | Dose | Duration | Tests performed | Significant effects | Reference |
|---|---|---|---|---|---|---|---|
| Trehalose | Saccharomyces cerevisiae | Cultured mouse neuroblastoma Neuro2a cells with tNhtt-eGFP expression (cellular model of Huntington's disease) | 50 µM | 3 days | tNhtt aggregation; MTT assay | Decreased tNhtt aggregation & increased cell viability | 32 |
| 3-week-old heterozygous huntington exon-1-transgenic mice, strain R6/2 (bearing 145 CAG repeats) | 2% in drinking water | 12 weeks | Nissl staining and immunohistochemistry (ubiquitin); rotarod; foot-printing; paw clasping phenotype | Decreased striatal atrophy and intranuclear polyglutamine aggregates in the motor cortex and striatum; improved motor dysfunction, paw clasping phenotype and survival | 32 | ||
| 3-week-old heterozygous huntington exon-1-transgenic mice, strain R6/2 (bearing 145 CAG repeats) injected i.c.v. with murine neural progenitor cell line C17.2 | 2% in drinking water | 10 weeks (cells injected at week 8) | Immunocytochemistry (Nestin, MAP-2, ubiquitin); western blot (expanded polyQ); paw-clasping phenotype; foot printing; rotarod; Y-maze | Trehalose alone and in combination with C17.2 cells decreased polyglutamine aggregates in striatum, increased striatal volume, extended life span, delayed onset and severity of paw clasping, improved motor function; combination treatment was more effective and also improved memory performance | 33 | ||
| 3-month-old ♂ or 14-month-old ♀ PK− / −/TauVLW mice (model of tauopathy with Parkinsonism) | 1% in drinking water | 3–12 weeks | Actimeter; stride length; Y-maze; immunohistochemistry (TH, total and phosphorylated tau, GFAP, A-beta); western blot; monoamine levels; glutathione assay | Trehalose improved motor function and anxiety and ameliorated tau pathology and astrogliosis; reversed dopaminergic deficits at 10 weeks; autophagy markers were increased | 34 | ||
| Fucoidan | Laminaria japonica | Cultured mouse dopaminergic cell line, MN9D, exposed to the neurotoxin MPP+ | 0.01, 0.1, or 1.0 mg/ml | 1 hours pretreatment + 36 hours cotreatment with MPP+ | LDH activity; MTT assay; morphology | 0.1 and 1.0 mg/ml doses reversed neuronal injury caused by MPP + | 35 |
| 8–10-week-old ♂ C57BL/6 mice injected i.p. with MPTP (model of Parkinson's) | 12.5 or 25 mg/kg i.p. | 18 days (MPTP injection on day 11) | Locomotor activity; dopamine, DOPAC and HVA levels in the striatum; immunohistochemistry and western blot (TH); oxidative stress and antioxidant capacity in the substantia nigra | Both doses differentially rescued locomotor deficits, prevented striatal depletion of dopamine and DOPAC, protected against the loss of TH-positive neurons and lipid peroxidation, and enhanced antioxidant activities in the substantia nigra | 35 | ||
| Fucus vesiculosus | Acutely dissociated Sprague–Dawley rat diagonal band of Broca forebrain neurons exposed to A-beta; primary rat basal forebrain cultures exposed to A-beta | Ranging from 50 to 1 µM | Active perfusion; 24 hours pretreatment or 48 hours cotreatment with A-beta | Whole-cell patch clamp; MTT and live/dead assays; immunohistochemistry (VAchT); electron microscopy for A-beta aggregation; DCF fluorescence; western blot (cleaved caspase-3; PKC phosphorylation) | 1 µM blocked the A-beta-induced reduction in whole-cell currents; 0.1 and 1 µM differentially protected against A-beta-induced apoptosis; 10 µM-induced apoptosis | 36 | |
| 7-day-old rats with unilateral cerebral hypoxia-ischemia | 25–500 mg/kg i.p. twice | Immediately before and after hypoxia exposure | MPO activity; RT-PCR and western blot (P-selectin); Nissl stain of brain slices | 25, 50, and 100 mg/kg doses attenuated brain damage induced by hypoxia-ischemia; >100 mg/kg doses exhibited toxic side effects | 38 | ||
| ♂ Sprague–Dawley rats with bolus collagenase-induced ICH | 30 µg/hour i.v. infusion | 7 days, beginning 30 minutes after ICH | MRI; spontaneous circling, ability to traverse a wooden beam; forelimb postural reflex; independent forelimb reaching and grasping in a staircase apparatus; passive avoidance | Increased size of hematoma, but improved motor function and memory retention | 37 | ||
| Polysaccharide fractions: J2 (xyloglucan); J3 (1.0 Rha: 1.3 Ara: 4.1 Xyl: 3.6 Gal: 9.1 Glu); J4 (0.3 Rha: 0.8 Ara: 0.1 Xyl: 0.1 Gal) | Nerium indicum | Primary rat cortical cultures exposed to serum-free media or A-beta peptides | 20 or 40 µg/ml of J2, J3, or J4 | 24 hours with serum-free media; 1 hours pretreatment + 24 hours with A-beta | DAPI staining; caspase-3 activity; western blot (PDK-1 and Akt phosphorylation) | All fractions and doses protected against serum-deprivation-induced and A-beta-induced apoptosis | 39 |
| Polysaccharide fraction: J6 (1.2 Rha: 2.0 Ara: 1.0 Xyl: 2.0 Gal) | Primary rat cortical cultures exposed to A-beta peptides | Ranging from 20 to 500 µg/ml | 1 hour pretreatment + 24 hours cotreatment with A-beta | DAPI staining; caspase-3 activity; LDH activity; western blot (cleaved caspase-3; p38 MAPK and Akt; JNK, MAPK and Akt phosphorylation) | 100, 250, or 500 µg/ml doses protected against A-beta-induced apoptosis; reduced cytotoxicity | 40 | |
| Polysaccharide fraction: LBA (6.2% w/w protein, 61 neutral sugars; 35.1 M% Ara, 10.0 Rha, 4.0 Xyl, 1.3 GluAc, 23.9 GalAc, 0.8 Man, 16.0 Gal, 8.9 Glu) | Lycium barbarum | Primary rat cortical cultures exposed to A-beta peptides | Ranging from 0.0001 to 100 µg/ml | 1 hour pretreatment + 24 hours cotreatment with A-beta; 1 hour pretreatment only (washout) | DAPI staining; morphology; caspase-3 activity; LDH activity; western blot (cleaved caspase-3; JNK and C-Jun phosphorylation) | 0.1, 1, 10, or 100 µg/ml differentially protected against A-beta-induced apoptosis | 42 |
| Primary rat cortical cultures exposed to glutamate | Ranging from 0.1 to 500 µg/ml | 24 hours with glutamate; 1 hour glutamate + 23 hours post-treatment | LDH activity; trypan blue stain; caspase-3 activity; western blot (JNK phosphorylation); nitroblue tetrazolium reduction | 10, 100, 250, or 500 µg/ml co- and post-treatment differentially protected against glutamate-induced cell death | 44 | ||
| Primary rat cortical cultures exposed to Hcy | Ranging from 0.1 to 500 µg/ml | 1 hour pretreatment + 24 hours Hcy; 1, 2, or 4 hours Hcy + 23, 22, or 20 hours post-treatment | DAPI staining; caspase-3 activity; LDH activity; western blot (cleaved caspase-3 and tau; tau, JNK, GSK-3 beta and ERK phosphorylation) | 100, 250, or 500 µg/ml pre- and post-treatment differentially protected against homocysteine-induced cell death | 45 | ||
| Polysaccharide fractions: LBB (4.99%w/w protein, 22 neutral sugars; 32.1 M% Ara, 31.2 Xyl, 1.4 GluAc, 3.2 GalAc, 2.9 Man, 15.9 Gal, 13.3 Glu); LBB-1 (3.35%w/w protein, 84 neutral sugars; 20.2 M% Ara, 8.1 Rha, 32.9 Xyl, 8.0 GluAc, 8.2 GalAc, 1.0 Man, 15.6 Gal, 5.3 Glu); LBB-II (5.82%w/w protein, 75 neutral sugars; 14.1 M% Ara, 15.8 Rha, 29.1 Xyl, 3.5 GluAc, 22.6 GalAc, 1.0 Man, 8.4 Gal, 5.5 Glu) | Primary rat cortical cultures exposed to A-beta peptides | Ranging from 0.1 to 500 µg/ml | 1 hour pretreatment + 24 hours cotreatment with A-beta | DAPI staining; caspase-3 activity; LDH activity; western blot (cleaved caspase-3; JNK and Akt phosphorylation) | 10, 100, or 500 µg/ml LBB, 10 or 100 µg/ml LBB-I or LBB-II differentially protected against A-beta-induced apoptosis | 41 | |
| Polysaccharide fractions: LBP (8.6%w/w protein, 18 neutral sugars; 16.1 M% Ara, 4.3 Rha, 2.8 Xyl, 14.4 GalAc, 1.5 Man, 12.9 Gal, 47.7 Glu, 0.3 NAcGlu); LBP-III (6.3%w/w protein, 15 neutral sugars; 6.1 M% Ara, 1.5 Rha, 92.4 GalAc) | Primary rat cortical cultures exposed to A-beta peptides | Ranging from 10 to 500 µg/ml | 1 hour pretreatment + 24 hours cotreatment with A-beta | Caspase activity; western blot (PKR phosphorylation) | 100 and 500 µg/ml LBP or LBP-III protected against A-beta-induced apoptosis | 43 | |
| Aqueous extract: VOA (30% w/w carb, 2 protein; 33.6 M% GalAc, 21.2 Ara, 18.9 Gal, 10.2 Rha, 4.7 Man, 9.4 Glu, 2 Xyl) | Verbena officinalis Linn. | Primary rat cortical cultures exposed to various toxins (A-beta peptides, tunicamycin, DTT, UV, and hydrogen peroxide) | 25–150 µg/ml | 1 hour pretreatment + 24 hours (A-beta or UV) or 16 hours (other toxins) | Caspase-2 and -3 activity; western blot (PKR and JNK phosphorylation, caspase-2 and -3); DAPI staining | 50, 75, 100, and 150 µg/ml differentially attenuated cytotoxic effects of A-beta and DTT | 46 |
Akt, serine/threonine kinase; Ara, arabinose; DAPI, 4′,6-diamidino-2-phenylindole; DCF, 2,7-dichlorofluorescin; DOPAC, 3,4-dihydroxyphenylacetic acid, DTT, dithiothreitol; ERK, extracellular signal-regulated kinase; Gal, galactose; GalAc, N-acetylgalactosamine, GFAP, glial fibrillary acidic protein; Glu, glucose; GluAc, N-acetylglucosamine; GSK, glycogen synthase kinase; HVA, homovanillic acid; Hcy, homocysteine; i.c.v., intracerebroventricular injection; ICH, intracerebral hemorrhage; i.p., intraperitoneal injection; i.v., intravenous injection; JNK, c-Jun N-terminal kinase; LDH, lactate dehydrogenase; Man, mannose; MAP-2, microtubule-associated protein 2; MAPK, mitogen-activated protein kinase; MPO, myeloperoxidase; MPP + , 1-methyl-4-phenylpyridinium; MPTP, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine; MRI, magnetic resonance imaging; MTT, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide; PDK-1, 3-phosphoinositide-dependent kinase 1; PK, parkin; PKC, protein kinase C; PKR, protein kinase R; Rha, rhamnose; RT-PCR, reverse transcription polymerase chain reaction; TH, tyrosine hydroxylase; tNhtt-eGFP, truncated N-terminal huntington fused to an enhanced green fluorescent protein; UV, ultraviolet; VAchT, vesicular acetylcholine transporter; Xyl, xylose.