epiglucan and Leukopenia

Euglena gracilis (EUG) is a food supplement rich in beta-glucans, which are stored in the form of granules called paramylon. We determined whether EUG improved chemotherapy-induced leukocytopenia and dysbiosis. Mice were orally administered EUG prior to gemcitabine treatment. Analyses of the blood cell count, leukocyte population in the spleen, granulocyte/macrophage-colony-stimulating factor (GM-CSF) production by splenocytes, and fecal microbiome were conducted. The recovery of total leukocytes, neutrophils, and monocytes was accelerated after a single gemcitabine treatment. A more rapid lymphocyte recovery rate was observed after four gemcitabine treatments. No difference was observed in the percentage of T, B, or myeloid cells or in the expression of Dectin-1 in the spleens of the gemcitabine and EUG/gemcitabine groups. The EUG/gemcitabine group showed an enhanced GM-CSF production by lipopolysaccharides-stimulated splenocytes. Next-generation sequencing revealed that gemcitabine-induced dysbiosis was alleviated. This study demonstrated that EUG-derived beta-glucans could act as a biological response modifier as well as prebiotics for ameliorating chemotherapy-induced adverse effects.

Topics: Administration, Oral; Animals; Antineoplastic Agents; beta-Glucans; Dysbiosis; Euglena gracilis; Glucans; Granulocyte-Macrophage Colony-Stimulating Factor; Leukopenia; Mice

The present study aimed to determine the effect of oral β-glucan on mucositis and leukopenia in 62 consecutive patients with colorectal cancer treated with an adjuvant FOLFOX-4 regimen. The patients were retrospectively evaluated in 2 groups: one group received β-glucan and the other did not (control group). Leucocytes, neutrophils, and platelets were evaluated before and 1 week after chemotherapy and oral mucositis and diarrhea were noted. Leucocyte and neutrophil counts after chemotherapy in the β-glucan group were 7,300/mm3 and 3,800/mm3, respectively, and the reductions, as compared to baseline, were not significant (p=0.673 and 0.784). The median platelet count was 264,000/mm3 after chemotherapy in the β-glucan group and the reduction, as compared to baseline, was borderline significant (p=0.048). In the control group, reduction in leucocyte, neutrophil, and platelet counts was statistically significant. Oral mucositis and diarrhea were less common in the β-glucan group. We conclude that β-glucan can be used to reduce the adverse effects of chemotherapy.

Topics: Adenocarcinoma; Administration, Oral; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; beta-Glucans; Chemotherapy, Adjuvant; Cohort Studies; Colorectal Neoplasms; Diarrhea; Female; Fluorouracil; Humans; Leucovorin; Leukocyte Count; Leukopenia; Male; Middle Aged; Mucositis; Organoplatinum Compounds; Platelet Count; Retrospective Studies; Stomatitis; Treatment Outcome

(1-->3)-beta-D-Glucans represent highly conserved structural components of cell walls in yeast, fungi, or seaweed. However, it is still unknown how they mediate their effects. The aim of this study was to evaluate both intraperitoneal and oral application of seaweed-derived (1-->3)-beta-D-glucan Phycarine. Phycarine showed significant stimulation of phagocytosis by peripheral blood cells. In addition, the efficiency of chemotherapy of Lewis lung carcinoma with cyclophosphamide was potentiated by Phycarine administration. Phycarine also strongly shortened the recovery of leucopenia caused either by chemotherapy or irradiation. Besides the role in stimulation of cellular immunity, we also found a significant increase of antibody formation. Using a suckling rat model for evaluation of the absorption and tissues distribution of enterally administered (125)I-Phycarine, we found that the majority of Phycarine was detected in the stomach and duodenum 5 min after the administration. This amount sharply decreased during first 30 min. A significant amount of Phycarine entered proximal intestine in a shortly after the gavage. Its transit through proximal intestine was decreasing with time and simultaneously increasing in the ileum. Systemic blood levels were very low (less than 0.5%). Taken together, these observations suggest that Phycarine is similarly effective both after i.p. and oral application, has very strong stimulating effects on three types of experimentally induced leucopenia and stimulates both humoral and cellular branch of immune reactions. The majority of Phycarine can be detected throughout the gastrointestinal tract, supporting the feasibility of enteral administration of Phycarine in the treatment of gastrointestinal diseases.

Topics: Administration, Oral; Animals; Antibody Formation; Apoptosis; beta-Glucans; Bone Marrow Cells; Carcinoma, Lewis Lung; Cell Count; Cyclophosphamide; Immunity, Cellular; Injections, Intraperitoneal; Iodine Radioisotopes; Killer Cells, Natural; Leukopenia; Mice; Mice, Inbred BALB C; Microspheres; Phagocytosis; Proteoglycans; Rats; Rats, Sprague-Dawley; Seaweed; Spleen; Thymus Gland; Tissue Distribution

SCG is a major 6-branched 1,3-beta-D-glucan in Sparassis crispa Fr. SCG shows antitumor activity and also enhances the hematopoietic response in cyclophosphamide (CY)-treated mice. In the present study, the molecular mechanism of the enhancement of the hematopoietic response was investigated. The levels of interferon-(IFN-)gamma, tumor necrosis factor-(TNF-)alpha, granulocyte-macrophage-colony stimulating factor (GM-CSF), interleukin-(IL-) 6 and IL-12p70 were significantly increased by SCG in CY-treated mice. GM-CSF production in the splenocytes from the CY-treated mice was higher than that in normal mice regardless of SCG stimulation. Neutralizing GM-CSF significantly inhibited the induction of IFN-gamma, TNF-alpha and IL-12p70 by SCG. The level of cytokine induction by SCG was regulated by the amount of endogenous GM-CSF produced in response to CY treatment in a dose-dependent manner. The expression of beta-glucan receptors, such as CR3 and dectin-1, was up-regulated by CY treatment. Blocking dectin-1 significantly inhibited the induction of TNF-alpha and IL-12p70 production by SCG. Taken together, these results suggest that the key factors in the cytokine induction in CY-treated mice were the enhanced levels of both endogenous GM-CSF production and dectin-1 expression.

Topics: Animals; Basidiomycota; beta-Glucans; Cyclophosphamide; Cytokines; Dose-Response Relationship, Drug; Drug Synergism; Granulocyte-Macrophage Colony-Stimulating Factor; Hematopoiesis; Immunologic Factors; Lectins, C-Type; Leukocyte Count; Leukopenia; Male; Membrane Proteins; Mice; Mice, Inbred C57BL; Nerve Tissue Proteins; Receptors, Immunologic; Spleen

Soy isoflavone aglycones (IFAs) have a wide range of biological actions that suggest they may be of use in cancer prevention. On the other hand, a branched beta-glucan from Sparassis crispa (SCG) is a major 6-branched 1,3-beta-D-glucan in an edible/medicinal mushroom: Sparassis crispa showing antitumor activity. We have previously reported that both oral and intraperitoneal administration of SCG enhanced the hematopoietic response in cyclophosphamide (CY)-induced leukopenic mice. In this study, we investigated the hematopoietic response due to IFA in combination with SCG in CY-induced leukopenic mice. The oral administration of IFA in combination with SCG synergistically enhanced the number of white blood cells, and increased spleen weight. Analyzing the leukocyte population by flow cytometry, the combination of IFA and SCG increased the number of monocytes and granulocytes in the spleen. Taken together, the combination of IFA and SCG synergistically provides the hematopoietic responses that are enhanced over IFA or SCG alone.

Topics: Administration, Oral; Agaricales; Animals; beta-Glucans; Cell Proliferation; Disease Models, Animal; Drug Administration Schedule; Drug Synergism; Drug Therapy, Combination; Flow Cytometry; Glycine max; Hematopoiesis; Hematopoietic System; Injections, Intraperitoneal; Isoflavones; Leukocyte Count; Leukopenia; Male; Mice; Mice, Inbred ICR; Plant Extracts; Solubility; Soybean Proteins; Spleen; Time Factors

Sparassis crispa Fr. is an edible mushroom recently cultivable in Japan. It contains a remarkably high content of 6-branched 1,3-beta-D-glucan showing antitumor activity. Using ion-exchange chromatography, a purified beta-glucan preparation, SCG, was prepared. In this study, we examined the hematopoietic response by SCG in cyclophosphamide (CY)-induced leukopenic mice. SCG enhanced the hematopoietic response in CY induced leukopenic mice by intraperitoneal routes over a wide range of concentrations. SCG enhanced the hematopoietic response in CY-treated mice by prior or post administration. Analyzing the leukocyte population by flow cytometry, monocytes and granulocytes in the peritoneal cavity, liver, spleen and bone marrow (BM) recovered faster than in the control group. The ratio of natural killer cells and gammadelta T cells in the liver, spleen and peritoneal cavity was also increased. In contrast, CD4+ CD8+ cells in the thymus were temporarily significantly decreased by the administration of SCG. Interleukin-6 (IL-6) production of CY+SCG-treated peritoneal exdated cells (PECs), spleen cells and bone marrow cells (BMCs) were higher than that of the CY-treated group. By in vitro culture of CY-treated PEC and spleen cells, IL-6 production was enhanced by the addition of SCG. These facts suggested the possibility that IL-6 might be a key cytokine for the enhanced hematopoietic response by SCG.

Topics: Animals; beta-Glucans; Cell Count; Cyclophosphamide; Disease Models, Animal; Dose-Response Relationship, Drug; Glucans; Injections, Intraperitoneal; Interleukin-6; Leukocytes; Leukopenia; Male; Mice; Mice, Inbred ICR; Organ Specificity; Polyporales

Sparassis crispa is an edible mushroom recently cultivable in Japan. Polysaccharide fractions were prepared from the cultured S. crispa by repeated extraction with hot water (SCHWE), cold NaOH (SCCA), and then hot NaOH (SCHA). HWE was further separated by 1 volume (SCHWE1v) or 4 volumes (SCHWE4v) of ethanol-precipitable fractions. By chemical, enzymic, and NMR analyses, the primary structures of SCHWE1v, SCCA, and SCHA were 6-branched 1,3-beta-glucan, having one branch in approximately every third mainchain unit. All of these fractions showed antitumor activity to the solid form of Sarcoma 180 in ICR mice with strong vascular dilation and hemorrhage reaction. These fractions also showed enhanced hematopoietic response to cyclophosphamide induced leukopenic mice following intraperitoneal or peroral administration.

Topics: Animals; Antineoplastic Agents; beta-Glucans; Disease Models, Animal; Drug Screening Assays, Antitumor; Glucans; Leukocyte Count; Leukopenia; Magnetic Resonance Spectroscopy; Male; Mice; Mice, Inbred ICR; Polyporales; Polysaccharides; Sarcoma 180; Structure-Activity Relationship

It has been suggested that the immunopharmacological activity of soluble (1-->3)-beta-D-glucan depends on its conformation in mice. In this study, we examined the relationship between the conformation of Sonifilan (SPG) and hematopietic responses in cyclophosphamide (Cy)-induced leukopenic mice. SPG, a high molecular weight (1-->3)-beta-D-glucan, has a triple helical conformation in water, and it was changed by treatment with aqueous sodium hydroxide to the single helical conformer (SPG-OH). The effects of SPG or SPG-OH on hematopoietic responses in cyclophosphamide induced leukopenic mice were investigated by monitoring i) gene expression of cytokines by RT-PCR, ii) protein synthesis of interleukin 6 (IL-6) by ELISA and iii) colony formation of bone marrow cells (BMC). The mice administered Cy and SPG or SPG-OH expressed and produced higher levels of IL-6 mRNA and protein than the mice administered only Cy. Gene expression of NK1.1 was also induced by Cy/SPG (or SPG-OH) treatment. Induced gene expression of stem cell factor (SCF) and macrophage-colony stimulating factor (M-CSF) by SPG/SPG-OH were also found in in vitro culture of BMC from Cy treated mice. These results strongly suggested that conformation of the glucans, single and triple helix, are independent of the hematopietic response.

Topics: Animals; Antineoplastic Agents; Base Sequence; beta-Glucans; Carbohydrate Conformation; Colony-Forming Units Assay; Cyclophosphamide; Cytokines; DNA Primers; Gene Expression; Glucans; Hematopoiesis; Interleukin-6; Leukocyte Count; Leukopenia; Macrophage Colony-Stimulating Factor; Mice; Mice, Inbred ICR; RNA, Messenger; Sizofiran; Stem Cell Factor