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 (LBP_3p)

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]

Ramberg et al. Nutrition Journal 2010 9:54   doi:10.1186/1475-2891-9-54