Table 1

Immunomodulatory Glucan Extracts: Oral Animal Studies

Source

Extract

Animal

Dose/day

Duration of study

Treatment

Effects

Reference


Agaricus

(A. blazei) subrufescens

α-1,6 and

α-1,4 glucans

8-week ♀ C3H/He mice (5/group)

100 mg/kg IG every 3 days

1 month

Healthy animals

↑ #s splenic T lymphocytes (Thy1.2, CD4+ and CD8+)

[24]



Aqueous

7-9-week ♂ Balb/cByJ mice (40/group)

1 ml 0.45N, 0.6N, or 3N aqueous extract

2 months

All doses ↑ serum IgG levels, CD3+ T cell populations and PML phagocytic activity

[22]


7-9-week male Balb/cByJ mice (40/group)

1 ml 0.45N, 0.6N, or 3N aqueous extract

10 weeks

IP injection of OVA at 4 weeks

0.6N and 3N ↑ levels of OVA-specific serum IgG 28 days post-immunization; all doses ↑ delayed-type hypersensitivity and TNF-α secreted from splenocytes at 10 weeks; 0.6N ↑ splenocyte proliferation at 10 weeks


5-6 -week ♀ BALB/cHsdOla mice (8/group × 2)

One 200 μl extract day 1, orogastric intubation

1 week

Injected IP fecal solution day 2

↓ CFU in blood of mice with severe peritonitis & improved overall survival rate in all peritonitis groups

[46]


6-week BALB/c nu/nu mice (7/group)

2.5 mg extract days 20-41, drinking water

41 days

Injected SC Sp-2 myeloma cells day 1

↓ tumor size & weight after 21 days treatment

[65]


Aqueous, acid treated

6-week ♀ C57BL/6 mice (10/group)

20, 100 or 500 μg/ml, drinking water

9 days

Injected IP human ovarian cancer cells day 1

500 μg/ml ↓ tumor weight

[66]


20, 100 or 500 μg/ml, drinking water

3 weeks

Injected IV murine lung cancer (3LL) cells

100 & 500 μg/ml ↓ #s metastatic tumors


Aqueous, with 200 ng/day

β-glucan

6-week ♀ BALB/c mice (10/group)

200 ng days 5-21

3 weeks

Injected Meth A tumor cells day 1

↓ tumor size & weight

[23]


2 weeks

Injected Meth A tumor cells

↑ cytotoxic T lymphocyte activity & spleen cell IFN-α protein


300 mg

5 days

Healthy animals

↑ splenic NK cell activity


Avena spp.

β-glucans (particulate)

6-7 -week ♀ C57BL/6 mice (7/group)

3 mg every 48 h, days 1-3

1 month

Oral E. vermiformis oocytes day 10

E. vermiformis fecal oocyte #s; increased intestinal anti-merozoite IgA; ↓ # of IL-4-secreting MLN cells

[42]


3 mg on alternating days, days 1-10

22 days

Injected IP Eimeria vermiformis day 10

E. vermiformis fecal oocyte #s; ↑ anti-merozoite intestinal IgA

[43]


β-glucans (soluble)

4-week ♂ CD-1 mice (24/group)

0.6 mg/ml 68% β-glucan, drinking water

1 month

Resting or exercise-stressed (days 8-10) animals administered HSV-1 IN

day 10

↓ morbidity in resting and exercise-stressed animals; ↓ mortality in exercise-stressed animals; pre-infection, ↑ Mø anti-viral resistance in resting and exercise-stressed animals

[38]



~3.5 mg days

1-10, drinking water

Resting or exercise-stressed (days 5-10) animals administered HSV-1 IN

day 10

Pre-infection, ↑ Mø antiviral resistance in resting animals

[41]


4-week ♂ CD-1 mice (10/group)

0.6 mg/ml 68% β-glucan, drinking water

10 days

Resting animals or animals exposed to a bout of fatiguing exercise days 8-10 or moderate exercise days 5-10, injected IP with thioglycollate on day 10

↑ neutrophil mobilization in resting & moderately exercised animals; ↑ neutrophil respiratory burst activity in resting and fatiguing exercised animals

[37]


4-week ♂ CD-1 mice (19-30/group)

0.8 mg/ml 50% β-glucan, days

1-10, drinking water

1 month

Resting or exercise-stressed (days 8-10) animals administered IN clodronate-filled liposomes to deplete Mø days 8 & 14 & infected IN with HSV-1 day 10

↓ morbidity, mortality, symptom severity in exercise-stressed animals, without Mø depletion

[40]



4-week ♂ CD-1 mice (20/group)

Resting or exercise-stressed (days 8-10) animals administered HSV-1 IN day 10

↓ morbidity in exercise-stressed & resting animals; ↓ mortality in exercise-stressed animals

[39]


Ganoderma lucidum

Aqueous

7-week ♂ CD-1 mice (26/group)

5% of diet

5 months

Injected IM DMH once a week, weeks 1-10

↓ aberrant crypt foci per colon, tumor size, cell proliferation, nuclear staining of β-catenin

[69]


4-8-week BALB/c mice (10/group)

50, 100 or 200 mg/kg, oral

10 days

Injected SD Sarcoma 180 cells

↓ of tumor weight was dose dependent: 27.7, 55.8, 66.7%, respectively

[67]


Ganoderma lucidum (mycelia)

Aqueous

7-week ♂ F344/Du Crj rats (16/group)

1.25% or 2.5% of diet

6 months

Injected SC AOM once a week, weeks2-5

Both doses ↓ colonic adenocarcinoma incidence; 2.5% ↓ total tumor incidence; both doses ↓ nuclear staining of β-catenin and cell proliferation

[68]


Ganoderma tsugae

Aqueous

8-week ♀ BALB/cByJNarl mice (14/group)

0.2-0.4% of diet (young fungi); 0.33 or 0.66% of diet (mature fungi)

5 weeks

Injected IP OVA days 7, 14, 21; aerosolized OVA twice during week 4

In splenocytes, both doses of both extracts ↑ IL-2 and IL-2/IL-4 ratios, 0.2% young extract and 0.66% mature extract ↓ IL-4; in Mø, 0.66% mature extract ↑ IL-1β, both doses of both extracts ↑ IL-6

[53]


Grifola frondosa

D fraction

Mice: 1) ICR, 2) C3H/HeN, 3) CDF1 (10/group)

1.5 mg every other day, beginning day 2

13 days

Implanted SC: 1) Sarcoma-180, 2) MM-46 carcinoma, or 3) IMC carcinoma cells

↓ tumor weight & tumor growth rate: 1) 58%, 2) 64%, and 3) 75%, respectively

[71]


5-week ♂ BALB/c mice (10/group)

2 mg,

days 15-30

45 days

Injected in the back with 3-MCA, day 1

↓ (62.5%) # of animals with tumors; ↑ H202 production by plasma Mø; ↑ cytotoxic T cell activity

[72]


Hordeum vulgare

β-1,3;1,4 or β-1,3;1,6-D-glucans

Athymic nu/nu mice

(4-12/group)

40 or 400 μg IG for 4 weeks

31 weeks

Mice with human xenografts (SKMel28 melanoma, A431 epidermoid carcinoma, BT474 breast carcinoma, Daudi lymphoma, or LAN-1 neuroblastoma) ± mAb (R24, 528, Herceptin, Rituximab, or 3F8, respectively) therapy twice weekly

400 μg + mAb ↓ tumor growth & ↑ survival; higher MW ↓ tumor growth rate for both doses

[75]


β-1,3;1,4-D-glucans

Athymic BALB/c mice

4, 40, or 400 μg for 3-4 weeks

1 month

Mice with neuroblastoma (NMB7, LAN-1, or SK-N-ER) xenografts, ± 3F8 mAb therapy twice weekly

40 and 400 μg doses + mAB ↓ tumor growth; 400 μg dose ↑ survival. Serum NK cells required for effects on tumor size

[76]


C57BL/6 WT and CR3-deficient mice (10/group)

0.4 mg for 3 weeks

100 days

Injected SC RMA-S-MUC1 lymphoma cells day 1 ± IV 14.G2a or anti-MUC1 mAb every 3rd day

±mAB ↓ tumor diameter; ↑ survival

[73]


β-glucans

♀ Fox Chase ICR immune-deficient (SCID) mice (9/group)

400 μg days 1-29

50 days

Mice with human (Daudi, EBV-BLCL, Hs445, or RPMI6666) lymphoma xenografts, ± Rituximab mAb therapy twice weekly

+mAB ↓ tumor growth and ↑ survival

[74]


Laminaria digitata

Laminarin

♂ ICR/HSD mice (3/group)

1 mg

1 day

Healthy animals

↑ Mø expression of Dectin-1 in GALT cells; ↑ TLR2 expression in Peyer's patch dendritic cells

[29]


♂ Wistar rats (7/group)

5% of diet days 1-4, 10% of diet days 5-25

26 days

Injected IP E. coli LPS day 25

↓ liver ALT, AST, and LDH enzyme levels; ↑ ED2-positive cells, .↓ peroxidase-positive cells in liver; ↓ serum monocytes, TNF-α, PGE2, NO2

[44]


Lentinula edodes

SME

6-week nude mice

0.1 ml water with10% SME/10 g body weight days 1-19, 33-50

50 days

Injected SC prostate cancer (PC-3) cells day 1

↓ tumor size

[80]


β-glucans

♀ 3- and 8-week BALB/c mice (15/group)

50, 100 or 250 μg

1-2 weeks

Healthy animals

250 μg dose ↑ spleen cell IL-2 secretion

[27]


♀ 3- and 8-week BALB/c mice (15/group)

50, 100 or 250 μg

1-2 weeks

Injected murine mammary carcinoma (Ptas64) cells into mammary fat pads 2 weeks before treatment

↓ tumor weight


Lentinan

6-week ♂ Wistar-Imamichi specific-pathogen free rats (10/group)

1 mg twice weekly

1-2 months

Healthy animals

↑ T cell #s, helper-cell #s & helper/suppressor ratio, ↓ suppressor cell level at 4, but not 8 weeks

[26]


5-6-week ♂

pre-leukemic AKR mice (10/group)

3 mg, days 1-7

3 weeks

Injected SC K36 murine lymphoma cells day 7

↓ tumor weight; ↑ tumor inhibition rate (94%)

[82]



5-6-week athymic mice (10/group)

5 weeks

Injected SC colon cancer (LoVo and SW48, SW480 and SW620, or SW403 and SW1116) cells day 7

↓ tumor weight, ↑ tumor inhibition rate (>90%)


♂ AKR mice

3 mg

1 day

Pre-leukemic mice

↑ serum IFN-α and TNF-α, peak at 4 h and then back to normal at 24 h; ↑ IL-2 and IL-1α, peak at 2 h and back to normal at 24 h; ↑ CD3+ T, CD4+ T, CD8+ T, B lymphocytes

[81]


Phellinus linteus

Aqueous, alcohol-precipitated

6-7-week C57BL/6 mice (10-50/group)

200 mg/kg in drinking water

1 month

Healthy animals

↑ production and secretion of IFN-γ by con A stimulated T cells

[32]


Saccharomyces cerevisiae

Scleroglucan

♂ ICR/HSD mice (3/group)

1 mg one day before challenge (day 1)

6 days

IV Staphylococcus aureus or Candida albicans day 2

↑ long-term survival

[29]


β-1,3;1,6 glucans (particulate)

3 and 8-week ♀ BALB/c mice (15/group)

50, 100 or 250 μg

1-2 weeks

Injected murine mammary carcinoma (Ptas64) cells into mammary fat pads 2 weeks before treatment

↓ tumor weight

[27]



β-1,3-glucan

Healthy animals

All 3 doses ↑ phagocytic activity of blood monocytes & neutrophils & ↑ spleen cell IL-2 secretion


WT or CCD11b-/- C57BL/6 mice (2/group)

0.4 mg for 3 weeks

100 days

Injected SC RMA-S-MUC1 lymphoma cells ± 14.G2a or anti-MUC1 mAb IV injection every 3rd day

↓ tumor diameter when included with mAb; ↑ survival with and without mAb

[73]


C57BL/6mice (4/group)

25 mg

1 week

Healthy animals

↑ # intestinal IELs; ↑ # TCRαβ+, TCR γδ+, CD8+, CD4+, CD8αα+, CD8αβ+ T cells in IELs; ↑ IFN-γ mRNA expression in IELs and spleen

[28]


Sclerotinia sclerotiorum

SSG

6-8-week specific pathogen-free ♂ CDF1 mice (3/group)

40 or 80 mg/kg days 1-10

2 weeks

Healthy animals

10 mg dose ↑ acid phosphatase activity of peritoneal Mø (day 14)

[30]


40, 80 or 160 mg/kg days 2-6

35 days

Implanted SC Metha A fibrosarcoma cells day 1

80 mg dose ↓ tumor weight



6-8-week specific pathogen-free ♂ CDF1 mice (10/group)

40, 80 or 160 mg/kg days 2-11

Injected ID IMC carcinoma cells day 1


6-8-week specific-pathogen free ♂ mice of BDF1 and C57BL/6 mice (7/group)

0.5, 1, 2, or 4 mg days 1-10

2-3 weeks

Injected IV Lewis lung carcinoma (3LL) cells

2 mg ↓ # of 3LL surface lung nodules at 2 weeks

[83]


Sclerotium rofsii

Glucan phosphate

♂ ICR/HSD mice (3/group)

1 mg

1 day

Healthy animals

↑ systemic IL-6; ↑ Mø expression of Dectin-1 in GALT cells; ↑ TLR2 expression in dendritic cells from Peyer's patches

[29]


Trametes (Coriolus) versicolor

PSP

6-8-week ♂ BALB/c mice (10/group)

35 μg days 5-29 in drinking water

29 days

Implanted SC Sarcoma-180 cells day 1

↓ tumor growth & vascular density

[94]


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

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