Shanghai Institute of Materia Medica, Chinese Academy of Sciences.
Abstract
A protein-bound polysaccharides (PSP) isolated from Coriolus versicolor in Shanghai, at the concentrations of 100-800 micrograms/ml promoted lymphocyte proliferation. PSP 25 mg/kg ip into mice for 5 d antagonized the inhibition of IL-2 production by cyclophosphamide from activated T lymphocytes and restored the suppressed T-cell-mediated delayed, type hypersensitivity response to normal. PSP 10-1000 micrograms/ml induced interferon alpha and gamma production from human peripheral leukocytes 4 and 8 times respectively higher than that of the control groups. Moreover, PSP also increased phagocytic functions of host reticulo-endothelial system. The results suggest that the anti-tumor effects of PSP may be related to its potentiation of host immunological responses.
Department of Food and Agricultural Chemistry, The Queen’s University of Belfast, and Food and Agricultural Chemistry Research Division, Department of Agriculture for Northern Ireland, Newforge Lane, Belfast BT9 5PX, Northern Ireland, and Department of Biology, Paisley College of Technology, Paisley PA1 2BE, Scotland, United Kingdom.
Abstract
Chloromethane, a gaseous natural product implicated in methylation processes in Phellinus pomaceus, has been shown to act as methyl donor in veratryl alcohol biosynthesis in the lignin-degrading fungi Phanerochaete chrysosporium, Phlebia radiata, and Coriolus versicolor, none of which released detectable amounts of CH(3)Cl during growth. When P. chrysosporium was grown in a medium containing CH(3)Cl, levels of CH(3) incorporation into the 3- and 4-O-methyl groups of veratryl alcohol were very high and initially similar to those observed when the medium was supplemented with l-[methyl-H(3)]methionine. When CH(3)Cl was added to cultures actively synthesizing veratryl alcohol, incorporation of CH(3) was very rapid, with 81% of veratryl alcohol labeled after 12 h. By contrast, incorporation of CH(3) from l-[methyl-H(3)]methionine was comparatively slow, attaining 10% after 12 h. It is proposed that these lignin-degrading fungi possess a tightly channeled multienzyme system in which CH(3)Cl biosynthesis is closely coupled to CH(3)Cl utilization for methylation of veratryl alcohol precursors.
Department of Dairy Microbiology, National Dairy Research Institute, Haryana, India.
Abstract
Bioconversion of wheat straw by solid-substrate fermentation (SSF) with Coriolus versicolor was optimized by varying its physiological parameters. Selective delignification (more lignin than holocellulose degradation) and increases in crude protein (CP) content and in vitro dry matter digestibility (IVDMD) were taken as the criteria to select optimum levels of these parameters. The fungus behaved optimally under the following set of cultural and nutritional conditions: pH 5.5, moisture level 55%, temperature 30 degrees C, duration of fermentation 21 d, form of inoculum–grain culture, turning frequency–once at mid-incubation, urea (nitrogen source) 1.5% (sterile) or 3.0% (nonsterile), single superphosphate (phosphorus + sulfur source) 1.0%, no addition of free polysaccharides (as whey or molasses). A maximum of 17.5% increase in IVDMD involving 4.3% degradation of lignin, was attained in the optimized SSF under laboratory conditions. The digestibility improvement could be further increased by using a substrate pretreatment (physical/chemical/biological) in the following order of preference: NaOH treatment, urea or urine treatment, ensiling, steaming, grinding. For practical farm applications, urea treatment and ensiling appeared most feasible. The laboratory optimized process was also scaled up to 4 kg (sterile and unsterile) and 50 kg (unsterile) fermentations.
First Department of Biochemistry, School of Medicine, Showa University, Tokyo, Japan.
Abstract
A protein-bound polysaccharide, PSK, extracted from the mycelium of Coriolus versicolor (Fr.) Quel, has been recognized for its host-mediated induction of antitumor and antimicrobial activities in mice. Intravenous administration of PSK, in association with OK-432 (Picibanil), transiently induced endogenous production of a cytotoxic factor (CF) (possibly tumor necrosis factor, TNF) in normal mice. The ability to produce CF depended greatly on both dose and interval between administration of the PSK and OK-432. Although PSK has been reported to contain several active ingredients, unfractionated PSK has been used in almost all experiments performed so far. We recently reported that, of the four subfractions separated by successive filtration through membrane filters, only the highest molecular weight fraction F4 (MW greater than 200 kD) induced significant antimicrobial activity in mice. PSK stimulated the NBT-reducing activity of mouse peritoneal macrophages and the iodination (incorporation of radioactive iodine into an acid-insoluble fraction) of human peripheral blood polymorphonuclear cells (PMN). Among the subfractions of PSK, the highest molecular weight fraction F4, and the fraction precipitated at pH 4.0-4.5 (Fr. 4), stimulated macrophage NBT-reducing activity and PMN iodination most. In contrast, natural and chemically modified glucans had little or no stimulating activity. PSK, F4 or Fr. 4 additively or synergistically stimulated TNF-induced cytotoxicity against L-929 cells, differentiation of human myelogenous leukemia cell lines toward monocytes/macrophages, and iodination of human peripheral blood PMN. The active PSK subfractions significantly reduced the down regulation of specific 125I-TNF or 125I-IFN-gamma binding to cellular receptors. These data suggest that (i) immunopotentiation activity of PSK might be ascribed, at least in part, to stimulation of cytokine action and production, and (ii) PSK might have some unique structural features.
Cancer Center, Kyushu University Hospital, Fukuoka, Japan.
Abstract
Effects of the immunomodulator PSK on the metabolism of 1-(2-tetrahydrofuryl)-5-fluorouracil (tegafur) to 5-fluorouracil (5-FU) were examined in 10 patients with advanced gastric cancer and who had undergone curative resection. PSK is a protein-bound preparation, extracted from Coriolus versicolor and belongs to Basidiomycetes. The 5-FU concentration in the plasma was 0.024 micrograms/ml at 15 min after the intravenous injection of 400 mg of tegafur and the area under the curve of 5-FU was 0.58 micrograms.h/ml. Following administration of PSK, 3 g/day for 8-14 months, there was no change in the plasma level of 5-FU, in any patient. As the clinical dose of PSK had no apparent influence on the metabolism of tegafur to 5-FU, the combination of PSK and tegafur can be prescribed to treat patients with advanced gastric cancer.
Department of Chemical Engineering, Faculty of Engineering, Catholic University of Chile, P.O. Box 6177, SantÃago, Chile.
Abstract
Our results show that all of the brown rot fungi tested produce oxalic acid in liquid as well as in semisolid cultures. Gloeophyllum trabeum, which accumulates the lowest amount of oxalic acid during decay of pine holocellulose, showed the highest polysaccharide-depolymerizing activity. Semisolid cultures inoculated with this fungus rapidly converted C-labeled oxalic acid to CO(2) during cellulose depolymerization. The other brown rot fungi also oxidized C-labeled oxalic acid, although less rapidly. In contrast, semisolid cultures inoculated with the white rot fungus Coriolus versicolor did not significantly catabolize the acid and did not depolymerize the holocellulose during decay. Semisolid cultures of G. trabeum amended with desferrioxamine, a specific iron-chelating agent, were unable to lower the degree of polymerization of cellulose or to oxidize C-labeled oxalic acid to the extent or at the rate that control cultures did. These results suggest that both iron and oxalic acid are involved in cellulose depolymerization by brown rot fungi.
First Department of Biochemistry, School of Medicine, Showa University, Tokyo, Japan.
Abstract
When mouse resident peritoneal macrophages were cultured with PSK (Krestin), a protein-bound polysaccharide extracted from Coriolus versicolor, they became enlarged and elongated and expressed higher NBT-reducing activity. PSK stimulated the production of differentiation-inducing factor and cytotoxic factor by the mouse macrophage-like cell line J774.1, and iodination (incorporation of radioactive iodine into an acid-insoluble fraction) and interleukin-1-like factor production by human peripheral blood monocytes. Among four different PSK subfractions, the highest molecular weight fraction (MW greater than 200 kD) was the most potent. Natural and chemically modified glucans had little or no activity. The data suggest that some unique structure of the highest molecular weight fraction of PSK directly stimulates the monocytes/macrophages.
Biomedical Research Laboratories, Kureha Chemical Industry, Co., Ltd., Tokyo, Japan.
Abstract
We investigated the effect of PSK, a protein-bound polysaccharide obtained from Coriolus versicolor of basidiomycetes, on antitumor immunity in tumor-bearing mice. PSK prolonged significantly the life span of C3H/He mice bearing syngeneic plasmacytoma X5563 in a schedule- and dose-dependent manner. PSK was most effective when administered at 100 mg/kg every other day ten times starting from the day after tumor inoculation. The administration of PSK enhanced significantly the cytostatic activity of peritoneal exudate plastic-adherent cells and the cytolytic activity of spleen cells after in vitro incubation with mitomycin C-treated tumor cells. In addition, PSK restored the cytokine-producing capacity of spleen cells suppressed in tumor-bearing mice after in vitro incubation with mitogen. Sera from tumor-bearing mice suppressed the activity of such effector cells as well as the interleukin 2-producing capacity of spleen cells, but sera from PSK-treated tumor-bearing mice prevented this suppression. These results suggest that PSK enhances antitumor immunity by reducing immunosuppressive activity of serum from tumor-bearing mice.
Department of Physiology, University of Hong Kong.
Abstract
A new small polypeptide was isolated from the crude extraction of polysaccharide peptide of Coriolus versicolor (Cov-1) by HPLC and CIEF. It has a smaller molecular weight (10K) compared with that of PSP (100K) and was named small peptide of Coriolus versicolor, SPCV. It was found that SPCV possesses potent cytotoxic effect on human tumor cell lines of HL-60, LS174-T, SMMU-7721, and SCG-7901. The IC50 of SPCV on HL-60 was 30 micrograms/ml. The inhibition rates of leukemia cells and SCG-7901 were significantly higher in SPCV treated group than that in PSP and PSK groups. SPCV also has immunopotentiating effect as it increased WBC and IgG levels. Pretreatment of SPCV for two weeks decreased the incidence of tumor mass in nude mice inoculated with tumor cells.
Molecular Biology Laboratory, Kitasato University School of Medicine, Kanagawa, Japan.
Abstract
The protein-bound polysaccharide of Coriolus versicolor QUEL (PS-K) has been found to express antioxidant activity as an “ion-radical scavenger” in diamine oxidation reactions. The mode of this expression was examined to determine whether the drug functioned as a simple radical scavenger or mimicked the action of superoxide dismutase (SOD). The latter was confirmed in both enzymatic and nonenzymatic superoxide anion radical (O2-.) producing systems in vitro. The SOD mimetic activity of PS-K was demonstrated by quantitative analysis of hydrogen peroxide as the end product of O2-., its formation being assisted catalytically by SOD or PS-K. Analysis by electron spin resonance also confirmed the SOD mimetic activity of PS-K in a xanthine-xanthine oxidase reaction. Relative SOD activity with PS-K was approximately 1/8,000 in a KO2-O2-.-producing system. The SOD mimetic activity of PS-K resisted treatment by 0.7N HCl, 0.7N NaOH, boiling for 30 minutes in a double water bath, and digestion by pronase. Fractionation according to differences in molecular mass caused no significant increase in relative SOD activity within a certain range of molecular mass, indicating that there is no definite molecule expressing SOD mimetic activity. Tumor-bearing rats and human patients with digestive tract cancer who suffered from oxidative stress were relieved by a single intraperitoneal administration of PS-K or a 1-day peroral prescription.