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] |