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Table 1 Immunomodulatory Glucan Extracts: Oral Animal Studies

From: Immunomodulatory dietary polysaccharides: a systematic review of the literature

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]
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