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PSK protects macrophages from lipoperoxide accumulation and foam cell formation caused by oxidatively modified low-density lipoprotein.

In previous works, it has been evidenced that lipoperoxidative injury to macrophages caused by oxidatively modified low-density lipoprotein (O-LDL) plays an important role in foam cell formation, and that PSK, a protein bound polysaccharide extracted from the class Basidiomycetes Coriolus Versicolor, can protect macrophages from lipoperoxidative injury induced by tert-butyl hydroperoxide (tbOOH). In this paper PSK protection of macrophages from lipoperoxide (LPO) accumulation and foam cell formation caused by O-LDL and its action mechanism were further studied. The LPO accumulation was determined by using ACAS 570. Dynamic assay of the LPO level in eight single cells after adding O-LDL or determination of the average LPO content in a lot of cells incubated in advance with O-LDL for 12 h, both indicated that O-LDL might induce LPO accumulation in macrophages and the effects of O-LDL could be prevented by PSK. O-LDL might cause the changes of morphological structure in macrophages and the transformation of macrophages into foam cells, and the effects could also be prevented by PSK. The determination of selenium-dependent glutathione peroxidase (SeGSHPx) activities and mRNA contents of macrophages and changes of SeGSHPx activity and mRNA content after incubation with tbOOH showed that PSK might increase the SeGSHPx activity of macrophage and the enhanced SeGSHPx activity may occur at the level of gene transcription.[…]

Examination of coumarins, flavonoids and polysaccharopeptide for antibacterial activity.

1. Coumarins, flavonoids and polysaccharopeptide were tested for antibacterial activity. 2. The bacteria used for this study included clinical isolates of Staphylococcus aureus, Shigella flexneri, Salmonella typhi, Escherichia coli and Pseudomonas aeruginosa. 3. Most of the coumarins tested failed to inhibit the bacteria at 25 mg/l. Edultin at 128 mg/l inhibited 4 of the 8 P. aeruginosa strains and 1 of the S. aureus strains tested. O-acetylcolumbianetin and imperatorin did not inhibit any isolate, even at 128 mg/l. 4. When tested at the dose of 128 mg/l, the flavonoids (rutin, naringin and baicalin) inhibited 25% or less of P. aeruginosa and only baicalin was active against S. aureus. 5. Arbutin and 4-(beta-D-glucopyranosyloxyl)-benzaldehyde inhibited 3 of the 8 P. aeruginosa strains when tested at 128 mg/l. 6. Polysaccharopeptide from the fungus Coriolus versicolor failed to inhibit any P. aeruginosa or S. aureus strain at 128 mg/l.[…]

Cloning and expression of pyranose oxidase cDNA from Coriolus versicolor in Escherichia coli.

Complementary DNA encoding pyranose oxidase (PROD) was cloned and sequenced for the first time from Coriolus versicolor. The nucleotide sequence revealed an open reading frame encoding a polypeptide composed of 623 amino acid residues. Compared with the experimentally determined N-terminal sequence of the PROD from C. versicolor. 38 amino acids from the N-terminus of the protein appeared to be eliminated during protein maturation. The cDNA was successfully expressed under the control of lacUV5 promoter in Escherichia coli at 25 degrees C, which will be beneficial in industrial production.[…]

Immunotherapy with low-dose interleukin-2 and a polysaccharopeptide derived from Coriolus versicolor.

The purpose of the present study was to evaluate the therapeutic efficacy of locally administered low-dose interleukin-2 (IL-2) and a polysaccharopeptide (PSP) derived from Cariolous versicolor in a herpes virus Type 2-transformed murine tumor (H238) model and to determine possible mechanisms of action. BALB/c mice were inoculated subcutaneously (s.c.) with H238 tumor cells and randomized into groups: a) no tumor and no treatment control, b) tumor and no treatment control, c) tumor + IL-2 at 0 to 4 days, d) tumor + PSP at 0 to 10 days, e) tumor + IL-2 at 0 to 4 days + PSP at 0 to 10 days, and f) tumor + IL-2 at 15 to 19 days + PSP at 15 to 25 days. The IL-2 was administered s.c. at 2 x 10(4) i.u./mouse/injection; PSP was given s.c. at 2 mg/mouse/injection. No obvious toxicity was noted during the treatments. IL-2 and, to a lesser extent, PSP significantly slowed (p < 0.05) tumor progression when given alone immediately after tumor cell injection. The combination of the two modalities did not significantly enhance the antitumor effect of IL-2 alone. However, mice receiving both agents had IL-2 in the plasma, their tumors expressed low levels of transforming growth factor-beta, and their splenocyte response to mitogenic stimulation was significantly higher than in untreated controls. Changes in blood leukocyte populations and splenic oxidative burst capacity were associated with tumor presence, but not with the type of treatment. In vitro assays showed that both IL-2 and PSP can suppress the uptake of 3H-thymidine by tumor cells and that the effect is more pronounced whent the agents are used in combination. These results indicate that IL-2 and PSP can slow progression of H238 tumors and that the mechanisms of action may be related to their direct cytotoxic effects, as well to their immunomodulatory properties.[…]

Polysaccharide peptide (PSP) restores immunosuppression induced by cyclophosphamide in rats.

Polysaccharide peptide (PSP) is a protein-bound polysaccharide extracted from an edible mushroom, Coriolus versicolor. Effects of PSP (2g/kg/day) on cyclophosphamide (CPA, 40 mg/kg/2 days)-induced immunosuppression were investigated by determining lymphocyte proliferation, Natural killer (NK) cell formation, IgG and IL-2 concentration, WBC count and the weight of organs after rats were treated with or without CPA in the presence or absence of PSP. The results demonstrated that PSP possessed immunopotentiating effect, being effective in restoring CPA-induced immunosuppression such as depressed lymphocyte proliferation, Natural Killer cell function, production on white blood cell and the growth of spleen and thymus in rats as well as in increasing both IgG and IL-2 production on which CPA did not have significant effects under the conditions of our experiments. PSP can partly restore CPA-induced immunosuppression. Based on our findings and the data accumulated so far, it was suggested that PSP should be considered as an useful adjuvant especially combined with CPA or other chemotherapy in clinical treatment of cancer patients. The mechanism by which PSP restores the immunosuppression induced by CPA is unclear.[…]

Polysaccharopeptide from Coriolus versicolor has potential for use against human immunodeficiency virus type 1 infection.

Polysaccharopeptide (PSP) isolated from the edible mushroom Coriolus versicolor was tested for its potential as an anti-human immunodeficiency virus type 1 (HIV-1) compound in a series of in vitro assays. It demonstrated inhibition of the interaction between HIV-1 gp 120 and immobilized CD4 receptor (IC50 = 150 microg/ml), potent inhibition of recombinant HIV-1 reverse transcriptase (IC50 = 6.25 microg/ml), and inhibited a glycohydrolase enzyme associated with viral glycosylation. These properties, coupled with its high solubility in water, heat-stability and low cytotoxicity, make it a useful compound for further studies on its possible use as an anti-viral agent in vivo.[…]

Dose intensity of uracil and tegafur in postoperative chemotherapy for patients with poorly differentiated gastric cancer.

A retrospective analysis of postoperative chemotherapy had shown the continuous administration of UFT, an oral preparation of 1-(2-tetrahydrofuryl)-5-fluorouracil (tegafur) and uracil at a molar ratio of 1:4, to be effective for poorly differentiated gastric cancer. We therefore sought to determine prospectively the effective dose of postoperative chemotherapy with UFT for patients with poorly differentiated gastric cancer following a curative resection. We determined the effect of the combined intravenous administration of mitomycin C (MMC) and oral treatment with protein-bound polysaccharide Kreha (PSK), extracted from the basidiomycete Coriolus versicolor, and UFT at a dose of either 8 mg/kg or 12 mg/kg daily for 1 year. A total of 224 patients with poorly differentiated stage II-IV gastric cancer were entered into this study after undergoing a curative resection. No differences were observed between the two treatment groups in terms of prognostic factors, the toxicity rate or the doses of the drugs prescribed, other than UFT. The higher dose of UFT in maintenance therapy led to a decrease in the recurrence rate (P < 0.05), and increases in disease-free survival and cause-specific survival (P < 0.05). UFT at 12 mg/kg in postoperative chemotherapy was thus found- to improve the postoperative results with no increase in toxicity for poorly differentiated gastric cancer, and is also cost-effective for outpatients.[…]

Fungal cleavage of thioether bond found in Yperite.

The degradation of thiodiglycol (I) and benzyl sulfide (II) was attempted using Coriolus versicolor and Tyromyces palustris to investigate the potential ability of basidiomycetes to degrade Yperite (bis(2-chloroethyl) sulfide), a mass-produced and stored chemical warfare agent. I was very rapidly degraded by both fungi. The metabolic pathway of II was elucidated, showing that the initial step was the hydrolytic cleavage of the thioether bond to yield benzyl alcohol and benzyl mercaptan. Benzyl alcohol was further oxidized and finally mineralized. Benzyl mercaptan is reversibly converted to benzyl disulfide and also converted to benzyl alcohol. Finally, the effective degradation of bis(2-bromoethyl) sulfide strongly suggests that basidiomycete would be a potential tool for Yperite degradation.[…]

Isolation of mRNAs induced by a hazardous chemical in white-rot fungus, Coriolus versicolor, by differential display.

White-rot fungus Coriolus versicolor, a ligninolytic basidiomycete, has been studied because of its ability to degrade hazardous chemicals. In this study, we searched for genes that are induced by a hazardous chemical using the mRNA differential-display technique and C. versicolor IFO30340 that has been exposed to pentachlorophenol (PCP). Five cDNA fragments were cloned and the DNA sequences of two fragments were analyzed in further detail. The clones corresponded to novel genes that have not previously been identified in C. versicolor. One of the cDNAs exhibited strong sequence homology to the gene for an enolase and the other exhibited homology to a heat shock protein. The expression of the two genes was up-regulated in PCP-treated C. versicolor.[…]

Polysaccharopeptide from the mushroom Coriolus versicolor possesses analgesic activity but does not produce adverse effects on female reproductive or embryonic development in mice.

1. Coriolus versicolor polysaccharopeptide has been reported to exert immunomodulatory and antitumor actions. The present study showed that it exhibits analgesic activity in the hot-plate test upon intraperitoneal administration to ICR mice. 2. It did not affect ovarian steroidogenesis, ovulation and midterm gestation in mice. It did not exert an adverse effect on mouse embryonic development either, as evidenced by the lack of an effect on somite number, axial length and the incidence of abnormalities in heartbeat, yolk sac circulation, optic vesicle, otic vesicle, shape of body axis, forelimb buds, branchial apparatus, cranial neural tube and head size. 3. Its analgesic activity would add to its attribute as an immunomodulatory and antitumor drug.[…]