Table 2.
Immunomodulatory Non-Glucan Extracts: Oral Animal Studies
| Extract | Source | Animal | Oral dose/day | Duration | Treatment | Significant effects | Reference |
|---|---|---|---|---|---|---|---|
| Fucoidans | Cladosiphon okamuranus Tokida | 8-week ♀ BALB/c mice, 10/group | 0.05% w/w of diet | 56 days | DSS-induced UC | ↓ disease activity index and myeloperoxidase activity; ↓ # of B220-positive colonic B cells; ↓ colonic MLN IFN-γ and IL-6 and ↑ IL-10 and TGF-β; ↓ colonic IgG; ↓ colonic epithelial cell IL-6, TNF-α, and TLR4 mRNA expression | [49] |
| Undaria pinnatifida | 5-week ♀ BALB/c mice (10-12/group) | 5 mg, days 1-14 or 7-14 | 2 weeks | Injected HSV into cornea day 7 | ↓ facial herpetic lesions; ↑ survival, particularly in pre-treated animals | [45] | |
| 10 mg | 1 week | Administered 5-fluorouracil |
↑ plasma NK cell activity | ||||
| Injected SC HSV | ↑ cytotoxic splenic T lymphocyte activity | ||||||
| 0.1 or 0.5 mg | 3 weeks | Injected IP HSV | Both doses ↑ serum neutralizing Ab titers, weeks 2 and 3 | ||||
| 6-week ♂ ddY mice (5/group) | 50, 100, 200 400 or 500 mg/kg days 1-28 |
3 weeks | Injected with Ehrlich carcinoma in back day 14 | 200-500 mg/kg ↓ tumor growth | [116] | ||
| 6-week ♂ BALB/c mice (8/group) | 40 mg/kg alternating days 7-19 |
19 days | Injected IP Meth A fibrosarcoma day 1 | ↓ tumor growth | |||
| Furanose (COLD-FX®) | Panax quinquefolium | Weanling ♂ SD rats (10/group) | 450 or 900 mg/kg in food |
1 week | Healthy animals | Both doses ↑ spleen Il-2 and IFN-γ production following ConA or LPS stimulation; ↓ proportion of total MLN and Peyer's patch CD3+ cells & activated T cells; high dose ↑ spleen cell IL-1β production following 48 h ConA stimulation. | [33] |
| Galacto-mannan (partially hydrolyzed guar gum) | Cyamopsis tetragonolobus | 10-week ♀ BALB/c mice, 11-15/group |
5% of diet | 3 weeks | DSS-induced UC at beginning of week 3 |
↓ disease activity index scores, ↓ colonic mucosal myeloperoxidase activity & lipid peroxidation; ↓ colonic TNF-α protein levels & mRNA expression up regulated by DSS exposure | [50] |
| Galacto-mannans (guar gum) |
8-month- SD rats, 5/group | 5% of diet | 3 weeks | Older animals | ↓ serum IgG; ↑ MLN lymphocyte IgA, IgM and IgG production | [36] | |
| Glucomannan (KS-2) | Lentinula edodes | DD1 mice (10-20/group) | 140 mg/kg days 2-13 |
50 days | Injected IP Ehrlich ascites tumor cells day 1 | ↑ survival | [84] |
| 0.1, 1, 10, or 100 mg/kg dose days 2-13 | 100 days | Injected Sarcoma-180 tumor cells day 1 |
1, 10, and 100 mg/kg doses ↑ survival | ||||
| Heteroglycan (ATOM) | A. subrufescens | Mice (10/group): 1) 5-week ♂ Swiss/NIH; 6 week- ♀ DS mice; 3) 8-week ♀ BALB/c nude; 4) 5-week C3H/HcN | 100 or 300 mg/kg days 2-11 |
8 weeks | Implanted SC 1) Sarcoma-180, 2) Shionogi carcinoma 42, 3) Meth A fibrosarcoma, or 4) Ehrlich ascites carcinoma cells | Both doses ↓ Sarcoma-180 tumor size at 4 weeks & ↑ survival; 300 mg/kg ↑ peritoneal macrophage and C3-positive cells; 300 mg/kg ↓ Shionogi and Meth A tumor sizes at 4 weeks. Both doses ↑ survival of Ehrlich ascites mice | [93] |
| Heteroglycan (LBP3p) | Lycium barbarum | ♂ Kunming mice (10/group) | 5, 10 or 20 mg/kg |
10 days | Injected SC Sarcoma-180 cells | 5 & 10 mg/kg ↑ thymus index; all doses ↓ weight, ↓ lipid peroxidation in serum, liver and spleen & ↑ spleen lymphocyte proliferation, cytotoxic T cell activity, IL-2 mRNA | [91] |
| Heteroglycan (PNPS-1) | Pholiota nameko | SD rats (5/group) | 100, 200 or 400 mg/kg days 1-8 | 8 days | Implanted SC cotton pellets in scapular region day 1 |
↓ granuloma growth positively correlated with dose: 11%, 18% and 44%, respectively | [55] |
| Heteroglycan (PG101) | Lentinus lepideus | 8-10-week ♀ BALB/c mice (3/group) | 10 mg | 24 days | 6 Gy gamma irradiation | ↑ colony forming cells, granulocyte CFUs/Mø, erythroid burst-forming units, and myeloid progenitor cells in bone marrow; induced proliferation of granulocyte progenitor cells in bone marrow; ↑ serum levels of GM-CSF, IL-6, IL-1β | [92] |
| Mixed poly-saccharides (Ambrotose® or Advanced Ambrotose® powders) | Aloe barbadensis, Larix spp, and other plant poly-saccharides | ♂ SD rats (10/group) | 37.7 or 377 mg/kg Ambrotose® powder or 57.4 or 574 mg/kg Advanced Ambrotose® powder | 2 weeks | 5% DSS in drinking water beginning day 6 | 574 mg/kg Advanced Ambrotose powder ↓ DAI scores; 377 mg/kg Ambrotose complex & both doses Advanced Ambrotose powder ↑ colon length and ↓ blood monocyte count | [52] |
| Pectin | Pyrus pyrifolia | 6-8-week ♂ BALB/c mice (11/group) | 100 μg days 1-7 |
22 days | Injected IP OVA day 7, provoked with OVA aerosol day 21 | bronchial fluid:↓ IFN-γ & ↑ IL-5; splenic cells: ↑ IFN-γ, ↓ IL-5; normalized pulmonary histopathological changes; ↓ serum IgE | [54] |
| Pectins (bupleurum 2IIc) | Bupleurum falcatum | 6-8-week ♀ specific-pathogen-free C3H/HeJ mice | 250 mg/kg | 1 week | Healthy animals | ↑ spleen cell proliferation | [35] |
| Pectins (highly methoxylated) | Malus spp. | 8-month- SD rats (5/group) | 5% of diet vs. cellulose control | 3 weeks | Older animals | ↑ MLN lymphocyte IgA & IgG | [36] |
| Pectins | Citrus spp. | 5-week ♀ F344 rats (30/group) | 15% of diet | 34 weeks | Injected SC AOM once a week, weeks 4-14 | ↓ colon tumor incidence | [86] |
| Malus spp. | 5-week ♀ BALB/c mice (6/group) | 5% of diet | 2 weeks | Healthy animals | ↑ fecal IgA and MLN CD4+/CD8+ T lymphocyte ratio & IL-2 & IFN-γ secretion by ConA-stimulated MLN lymphocytes | [51] | |
| 5-week ♀ BALB/c mice (6/group) | 5% of diet days 5-19 vs. cellulose control | 19 days | DSS-induced UC days 1-5 | Significantly increased MLN lymphocytes IgA, and significantly decreased IgE; significantly decreased ConA-stimulated IL-4 and IL-10 | |||
| 4-week ♂ Donryu rats (20-21/group) | 20% of diet | 32 weeks | Injected SC AOM once a week, weeks 2-12 |
↓ colon tumor incidence | [85] | ||
| 4-week ♂ Donryu rats (19-20/group) | 10 or 20% of diet | 32 weeks | Injected SC AOM once a week, weeks 2-12 |
Both doses ↓ colon tumor incidence; 20% ↓ tumor occupied area & ↓ portal blood and distal colon PGE2 | [90] | ||
| Pectins (modified) | Citrus spp. | 2-4-month BALB/c mice (9-10/group) | 0.8 or 1.6 mg/ml drinking water, days 8-20 |
20 days | Injected SC with 2 × 2 mm section of human colon-25 tumor on day 1 | Both doses ↓ tumor size | [87] |
| NCR nu/nu mice (10/group) | 1% (w/v) drinking water | 16 weeks | Orthotopically injected human breast carcinoma cells (MDA-MB-435) into mammary fat pad on day 7 | ↓ tumor growth rate & volume at 7 weeks, lung metastases at 15 weeks, # of blood vessels/tumor at 33 days post-injection | [89] | ||
| NCR nu/nu mice (10/group) | 1% (w/v) drinking water | 7 weeks | Injected human colon carcinoma cells (LSLiL6) into cecum on day 7 | ↓ tumor weights and metastases to the lymph nodes and liver | |||
| SD rats (7-8/group) | 0.01%, 0.1% or 1.0% wt/vol of drinking water, days 4-30 | 1 month | Injected SC MAT-LyLu rat prostate cancer cells | 0.1% and 1.0% ↓ lung metastases; 1.0% ↓ lymph node disease incidence | [88] | ||