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Effect of polysaccharide peptide (PSP) on in vivo sulphation and glucuronidation of paracetamol in the rat.

Yeung JH, Chiu LC, Ooi VE.

Department of Pharmacology, Chinese University of Hong Kong, Shatin.

Abstract

The effect of polysaccharide peptide (PSP), an immunomodulator isolated from Coriolus versicolor COV-1, on the disposition of paracetamol was investigated in the rat. PSP (100 and 200 mg/kg, i.v.) was administered 30 min before a moderate dose (100 mg/kg, i.v.) of paracetamol was given. Plasma and bile concentrations of paracetamol, paracetamol glucuronide and paracetamol sulphate were measured by high performance liquid chromatography. The pharmacokinetics of paracetamol (100 mg/kg) alone was consistent with those reported previously, using a one-compartment model. PSP (200 mg/kg) significantly (P < 0.05) increased the clearance (controls, 19.06 +/- 2.74 ml/min/kg: PSP treated, 26.22 +/- 0.84 ml/min/kg) and volume of distribution (controls, 1.35 +/- 0.11 l/kg: PSP treated, 1.61 +/- 0.04 l/kg) of paracetamol by 37% and 21%, respectively. These changes were associated with concomitant increases in the glucuronide and sulphate metabolites in plasma, with significant increases in the Cmax and Tmax for both metabolites. The biliary excretion rate of paracetamol glucuronide and paracetamol sulphate were also measured. The Cmax values of paracetamol sulphate were significantly (P < 0.01) increased by 2.4-fold from 907.8 +/- 157.7 micrograms/ml (controls) to 3061 +/- 331 micrograms/ml after PSP treatment. The lower dose of PSP (100 mg/kg) had no significant effect on the disposition of paracetamol in this study, which agreed with previous reports that a low dose of PSP (100-200 mg/kg, i.p.) was less effective in the protection against paracetamol-induced hepatotoxicity. The time course of the increase in paracetamol sulphate in plasma and bile in this study coincided with the transient perturbation of glutathione (GSH) turnover by a similar dose range of PSP previously described, such that more cysteine was available for oxidation to inorganic sulphate. This increase in sulphate conjugation by PSP would, in part, contribute to the increase in disposition of paracetamol and may be related to the ability of PSP to decrease the covalent binding of paracetamol to microsomal proteins previously reported. Further studies are necessary to understand the mechanism(s) involved in the PSP-induced increases in paracetamol glucuronide and paracetamol sulphate formation and biliary excretion.

PMID: 8983934 [PubMed – indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov/pubmed/8983934

Effect of polysaccharide-peptide (PSP), an extract from yun-zhi, on chemotherapy-induced cytopenias.

Zhou LQ, Koo WH, Ang PT.

Department of Medical Oncology, Singapore General Hospital, Singapore.

Abstract

Polysaccharide-peptide (PSP) is a protein-bound complex carbohydrate derived from mycelia extract of Chinese fungus coriolus versicolor, or better known as Yun-Zhi. It has been shown to inhibit growth of cultured tumour cells, and it prevents cytotoxic-induced bone marrow suppression. An animal study was conducted with 24 Wistar rats to verify the myeloprotective effect of PSP. The rats were divided into two equal groups: group A (given cyclophosphamide [CTX]) and group B (given PSP and CTX). The body weights were similar in both groups of rats. In phase 1, all rats were given intravenous CTX 75 mg/kg. In addition, B rats received PSP 20 mg/day orally from 7 days before CTX to 14 days after CTX. Phase 2 was carried out two weeks after full recovery from CTX-induced cytopenia. The CTX was decreased to 60 mg/kg, and the group B rats received an increased dose of PSP 1.2 g/day for the same 21 days. In both phases, the CTX was well tolerated. Nadir white blood cell count was reached on day 4 and all counts recovered by day 10. There was no difference in absolute neutrophil, lymphocyte and platelet counts between groups A and B. We concluded that oral PSP did not prevent CTX-induced cytopenia in rats.

PMID: 8779535 [PubMed – indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov/pubmed/8779535

Morphological study of cytotoxicity produced by PSK-induced polymorphonuclear leukocytes (PMNs) and Nocardia rubra cell wall skeleton.

Kata H, Inoue M, Mukai S, Kawahito Y, Yoshida T, Asai K, Kimura S, Hashiramoto A, Yamamura Y, Sano H, Sugino S, Kondo M.

First Department of Internal Medicine, Kyoto Prefectural University of Medicine, Japan.

Abstract

The morphologic changes in PMNs induced by an i.p. injection of PSK, a polysaccharide from the mycelia of Coriolus versicolor, and tumor cells undergoing cell death, were evaluated by immunohistochemical staining and electron microscopy. Male C3H/He mice, 8-10 -weeks old, received an i.p. injection of 125 mg/kg of PSK. Their PMNs were obtained 6 h after the PSK injection by peritoneal lavage. N-CWS (Nocardia rubra cell wall skeleton) was added at the start of the chromium release assay using the MM46 mammary carcinoma cell line, which is syngeneic to C3H/He mice, as target cells. During the cytotoxic assay, the cells were fixed at various time points. The MM46 cells expressed ICAM-1 while the PMNs expressed both ICAM-1 and LFA-1 as determined by immunohistochemical staining and immunoelectron microscopy using anti-ICAM-1 and anti-LFA-1 antibodies. PMNs with ruffle-like microvilli adhered to the MM46 tumor cells 30 min after the addition of N-CWS. Immunoelectron microscopic findings suggested that the adhesion molecules were LFA-1 on the PMNs and ICAM-1 on the MM46 tumor cells, but cell fusion between the PMNs and tumor cells was not observed. The MM46 tumor cells gradually lost their microvilli, which showed cell damage, and died 6-7 h after the addition of the N-CWS. This time course of tumor cell death is compatible with the results of the cytotoxic assay. Pretreatment of PMNs by anti-LFA-1 antibody suppressed 1% lysis of MM46 tumor cells from 90% to 10% (p < 0.01). These data suggest that adhesion molecule on the surface of PMNs such as LFA-1 might play an important role on signal transduction of these PMNs cytotoxic function in this experimental system.

PMID: 9012542 [PubMed – indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov/pubmed/9012542

Restorative effect of Coriolus versicolor polysaccharides against gamma-irradiation-induced spleen injury in mice.

Lin IH, Hau DM, Chang YH.

Institute of Radiation Biology, National Tsing-Hua University, Taiwan, China.

Abstract

AIM: To study the restorative effect of Coriolus versicolor polysaccharides (CVP) on spleen injury induced by gamma-ray irradiation in mice.

METHODS: ICR Male mice, 6-8 wk old, were divided at random into 3 groups: A) normal control; B) irradiated with 1 Gy; and C) after 1 Gy irradiation, given CVP 60 mg.kg-1 (ig) daily for 10 d continuously. Body weight (BW), spleen weight (SW), relative SW (RSW), DNA synthesis of splenocytes (DNA-SS), and relative DNA-SS were measured on d 5, 12, 19, 26, and 33 after irradiation.

RESULTS: SW, RSW, DNA-SS, and relative DNA-SS decreased after irradiation. CVP enhanced the recovery of SW, RSW, DNA-SS, and relative DNA-SS inhibited by irradiation.

CONCLUSION: CVP has the restorative effect against spleen injury induced by gamma-ray irradiation in mice.

PMID: 9772653 [PubMed – indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov/pubmed/9772653

Effects of Coriolus versicolor polysaccharides on superoxide dismutase activities in mice.

Wei WS, Tan JQ, Guo F, Ghen HS, Zhou ZY, Zhang ZH, Gui L.

Department of Pharmacology, Second Military Medical University, Shanghai, China.

Abstract

AIM: To study if Coriolus versicolor polysaccharides (CVP) influence the superoxide dismutase (SOD) activities in mice.

METHODS: Normal, tumor-bearing, and radiated ICR mice were injected ip with CVP daily for 3-15 d. The SOD activity was assayed by epinephrine autoxidation test.

RESULTS: The SOD activities in lymphocytes and thymus were increased by CVP in both the normal mice with or without delayed hypersensitivity (DH). In tumor-bearing mice, CVP exerted not only inhibitory effects on tumor, growth and SOD activity in tumor tissue but also complete or partial restorative effects on the suppressed DH and on the declined SOD activities in lymphocytes, spleen, and thymus. The total SOD and manganese-containing SOD (MnSOD) activities in lymphocytes and thymus were dose-dependently enhanced by CVP (5-20 mg.kg-1) on d 3 after the tumor transplantation. In the mice exposed to 60Co (3 or 6 Gy), DH and SOD activities were dose-dependently decreased. These changes were completely or partly prevented by CVP.

CONCLUSION: CVP exerted the favorable effects on SOD activities in mice. Coriolus versicolor polysaccharides (CVP) exert inhibitory effects on experimental and clinical tumors. These effects are presumed to be mediated mainly by host-defence mechanism, especially immunological responeses. Superoxide dismutase (SOD) plays an important role in protecting cells against superoxide radical (O2-.) damages and over-production of O2-. or SOD abnormities exist in many diseases. The present study was to investigate if the CVP could exert some favorable effects on SOD activities in vivo.

PMID: 9772673 [PubMed – indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov/pubmed/9772673

The ligninolytic system of the white rot fungus Pycnoporus cinnabarinus: purification and characterization of the laccase.

Eggert C, Temp U, Eriksson KE.

Department of Biochemistry and Molecular Biology, University of Georgia, Athens 30602-7229, USA.

Abstract

The white rot fungus Pycnoporus cinnabarinus was characterized with respect to its set of extracellular phenoloxidases. Laccase was produced as the predominant extracellular phenoloxidase in conjunction with low amounts of an unusual peroxidase. Neither lignin peroxidase nor manganese peroxidase was detected. Laccase was produced constitutively during primary metabolism. Addition of the most effective inducer, 2,5-xylidine, enhanced laccase production ninefold without altering the isoenzyme pattern of the enzyme. Laccase purified to apparent homogeneity was a single polypeptide having a molecular mass of approximately 81,000 Da, as determined by calibrated gel filtration chromatography, and a carbohydrate content of 9%. The enzyme displayed an unusual behavior on isoelectric focusing gels; the activity was split into one major band (pI, 3.7) and several minor bands of decreasing intensity which appeared at regular, closely spaced intervals toward the alkaline end of the gel. Repeated electrophoresis of the major band under identical conditions produced the same pattern, suggesting that the laccase was secreted as a single acidic isoform with a pI of about 3.7 and that the multiband pattern was an artifact produced by electrophoresis. This appeared to be confirmed by N-terminal amino acid sequencing of the purified enzyme, which yielded a single sequence for the first 21 residues. Spectroscopic analysis indicated a typical laccase active site in the P. cinnabarinus enzyme since all three typical Cu(II)-type centers were identified. Substrate specificity and inhibitor studies also indicated the enzyme to be a typical fungal laccase. The N-terminal amino acid sequence of the P. cinnabarinus laccase showed close homology to the N-terminal sequences determined for laccases from Trametes versicolor, Coriolus hirsutus, and an unidentified basidiomycete, PM1. The principal features of the P. cinnabarinus enzyme system, a single predominant laccase and a lack of lignin- or manganese-type peroxidase, make this organism an interesting model for further studies of possible alternative pathways of lignin degradation by white rot fungi.

PMID: 8919775 [PubMed – indexed for MEDLINE]PMCID: PMC167880Free PMC Article

http://www.ncbi.nlm.nih.gov/pubmed/8919775

A cluster of genes encoding major isozymes of lignin peroxidase and manganese peroxidase from the white-rot fungus Trametes versicolor.

Johansson T, Nyman PO.

Department of Biochemistry, Lund University, Sweden. johansson@biokem.lu.se.

Abstract

A gene cluster from the white-rot basidiomycete Trametes (Coriolus) versicolor (Tv) PRL 572 containing three structural genes, LPGIII, LPGIV and MPGI, was characterized. The genes are arranged in the same transcriptional direction, within a 10-kb region, and found to encode quantitatively dominant isozymes of lignin peroxidase (LP) and manganese peroxidase (MP). The second gene in sequence, LPGIV, predicts a 346-amino-acid (aa) mature polypeptide (36.9 kDa, pI 4.31) which is identical with the partial aa sequence information available on the LP12 isozyme (43.1 kDa, pI 3.27). The first gene, LPGIII, encodes a 341-aa polypeptide (36.1 kDa, pI 3.93) which has not been identified at the protein level. However, the similarity of LPGIV would suggest that the predicted product is an LP-type enzyme. LPGIII and LPGIV are homologous to the tandemly arranged genes LPGII and LPGI, respectively, recently described by Jönsson and Nyman [Biochim. Biophys. Acta 1218 (1994) 408-412]. The homologous genes, LPGIII/LPGII and LPGIV/LPGI, are 99% and 96% identical in sequence, respectively, and are predicted to encode identical polypeptides, since base substitutions in the predicted exons are all synonymous. The third gene, MPGI, is different in intron-exon organization and predicted to be disrupted by five rather than six introns, as are the LP genes. The deduced polypeptide, 339 aa in size (35.9 kDa, pI 4.07), is identical with the partial aa sequence information available for isozyme MP2 (44.5 kDa, pI 3.09). The MPGI- and LPGIV-encoded polypeptides are 70% identical in sequence which suggests that MP and LP from Tv may be regarded as members of the same family within the plant peroxidase superfamily. Most importantly, this study identifies a gene encoding the MP2 isozyme, and further shows that genes encoding MP and LP can be closely linked on the chromosome and may be coordinately transcribed.

PMID: 8621085 [PubMed – indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov/pubmed/8621085

Polysaccharide-peptide complexes from the cultured mycelia of the mushroom Coriolus versicolor and their culture medium activate mouse lymphocytes and macrophages.

Wang HX, NG TB, Liu WK, Ooi VE, Chang ST.

Department of Biology, Chinese University of Hong Kong, Shatin, Hong Kong.

Abstract

The aim of this study was to investigate the effects of the mushroom Coriolus versicolor on cells of the immune system. The cultured mycelia of the mushroom Coriolus versicolor and their culture medium were separately extracted with boiling water. The resulting polysaccharopeptide preparations were designated intramycelial (IM) and extramycelial materials (EM), and were separated by gel filtration before determining their effects on lymphocytes and macrophages in vitro and in vivo. After gel filtration on Sepharose 6B, only a single peak with a molecular weight of 13-19 KDa was obtained. Gel filtration of IM and EM on Sephadex G-50 revealed the presence of a larger peak of 28 KDa (from IM) and 15 KDa (from EM) and a smaller peak of 3.5 KDa. IM, EM and their large molecular peaks enhanced the mitogenic response of T-cells from BALB/c mice in vitro. Splenocytes from C57BL/6 mice pre-treated by force-feeding with IM and EM demonstrated an augmented mitogenic response to Con A. The macrophages of C57BL/6 mice that had been pre-treated with IM or EM showed an enhanced production of nitrite ions. The results indicate that both mouse lymphocytes and macrophages were activated by preparations of polysaccharopeptide from cultured mycelia and culture medium of C. versicolor. However, no direct cytotoxic activity against fibroblasts, hepatoma cells and choriocarcinoma cells could be demonstrated.

PMID: 8697105 [PubMed – indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov/pubmed/8697105

Antitumor effects of a refined polysaccharide peptide fraction isolated from Coriolus versicolor: in vitro and in vivo studies.

Dong Y, Kwan CY, Chen ZN, Yang MM.

Department of Physiology, Faculty of Medicine, University of Hong Kong, Pokfulam, Hong Kong.

Abstract

RPSP, a refined polysaccharide peptide fraction isolated by fast performance liquid chromatography (FPLC) from the crude powder of total peptide-bound polysaccharides of cultivated Coriolus versicolor Cov-1 dose-dependently inhibited the proliferation of a human hepatoma cell line (HEPG2). The effective dose causing 50% inhibition following 3-day exposure to RPSP was 243 +/- 36 micrograms/ml for HEPG2. However, little or no inhibitory effects were detected in normal human foetal hepatocytes. On the other hand, in the pretreatment group, in which RPSP was administered i.p. for two weeks before sarcoma 180 inoculation in nude mice, the incidence of tumor growth was less (2 out of 5 mice) than that of the control group (all 5 mice). The tumor size of the control group was about 3-5 times bigger than that of the pretreatment group. In tumor-bearing nude mice, 5 days after sarcoma 180 inoculation, i.v. administration of RPSP significantly suppressed the growth of tumor mass. The inhibition rate was 93.6% on day 13. Furthermore, administration of RPSP did not cause any pathological lesions in vital organs of rabbits such as heart, liver, spleen, lung and kidney. In conclusion, these results indicate that RPSP acts by directly suppressing tumor cell growth in vitro and the prevention of in vivo growth of tumor mass is probably mediated also via its immunomodulating effects.

PMID: 8774067 [PubMed – indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov/pubmed/8774067

Effects of Coriolus versicolor polysaccharides peptides on electric activity of mediobasal hypothalamus and on immune function in rats.

Yu GD, Yin QZ, Hu YM, Yin ZW, Gu ZL, Qian ZN, Qian ZM.

Laboratory of Neurobiology, Suzhou Medical College, China.

Abstract

AIM: The nervous mechanism of the immune potentiating effect of Coriolus versicolor polysaccharides peptides (PSP) was studied in Wistar rats.

METHODS: The unit discharge of the mediobasal hypothalamus (MBH) neurons was recorded extracellularly and the lymphocyte proliferation was measured.

RESULTS: PSP 1 g.kg-1 ig for 5 d increased the T-lymphocytes and promoted T-lymphocyte proliferation in spleen and peripheral blood. This promoting effect of PSP was blocked by MBH lesion. PSP increased the discharge frequency of MBH neurons, but no increase in discharge frequency was observed after treatment of PSP plus immune inhibitor, cyclosporin A.

CONCLUSION: MBH is involved in the immune-potentiating effect of PSP.

PMID: 9812756 [PubMed – indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov/pubmed/9812756