Effects of polysaccharide peptide (PSP) from Coriolus versicolor on the pharmacokinetics of cyclophosphamide in the rat and cytotoxicity in HepG2 cells

Chan SL, Yeung JH.

Department of Pharmacology, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong SAR, China. cslkel@hotmail.com

Abstract

Polysaccharide peptide (PSP), isolated from Coriolus versicolor COV-1, has been shown to restore the immunological effects against cyclophosphamide-induced immuno-suppression, although the mechanism(s) involved remain uncertain. This study investigated the PSP-cyclophosphamide interaction by studying the effects of PSP on the pharmacokinetic of cyclophosphamide in the rat and the effect of PSP on the cytotoxic effects of cyclophosphamide on a cancer cell line (HepG2 cells). In the pharmacokinetic studies in the rat, acute pre-treatment of PSP (4 micromol/kg/day, i.p.) decreased the clearance (CL) of cyclophosphamide by 31%, with a concomitant increase in the area under concentration-time curve (AUC) by 44%, and prolongation of the plasma half-life (T(1/2)) by 43%. Sub-chronic pre-treatment of PSP (2 micromol/kg/day, i.p., 3 days) decreased the CL of cyclophosphamide by 33%, with a concomitant increase in the AUC by 50%, and prolongation of the plasma T(1/2) by 34%. In cytotoxicity studies using HepG2 cells, non-toxic dose of PSP (1-10 microM) enhanced the cytotoxicity of cyclophosphamide. PSP at 10 microM further decreased HepG2 cell viability by 22% compared to when cyclophosphamide was present alone. In summary, PSP enhanced the cytotoxic effect of cyclophosphamide on a cancer cell line in vitro and altered the pharmacokinetics of cyclophosphamide in vivo in the rat. Both of these effects may be beneficial in the use of PSP as an adjunct to cyclophosphamide treatment.

PMID: 16297519 [PubMed – indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov/pubmed/16297519

Polysaccharide peptides from COV-1 strain of Coriolus versicolor induce hyperalgesia via inflammatory mediator release in the mouse.

Polysaccharide peptide (PSP), isolated from Coriolus versicolor COV-1, has been widely used as an adjunct to cancer chemotherapy and as an immuno-stimulator in China. In this study, the anti-nociceptive effects of PSP were investigated in two different pain models in the mouse. In the acetic acid-induced writhing model, initial studies showed that PSP decreased the number of acetic acid-induced writhing by 92.9%, which, by definition, would constitute an analgesic effect. However, further studies showed that PSP itself induced a dose-dependent writhing response. Studies on inflammatory mediator release showed that PSP increased the release of prostaglandin E2, tumor necrosis factor-alpha, interleukin-1beta, and histamine in mouse peritoneal macrophages and mast cells both in vitro and in vivo. The role of inflammatory mediator release in PSP-induced writhing was confirmed when diclofenac and dexamethasone decreased the number of writhing responses by 54% and 58.5%, respectively. Diphenhydramine totally inhibited the PSP-induced writhhttp://mushroomstudies.co/wp-admin/post-new.phping. In the hot-plate test, PSP dose-dependently shortened the hind paw withdrawal latency, indicative of a hyperalgesic effect. The hyperalgesic effect was reduced by pretreatment with the anti-inflammatory drugs. In conclusion, the PSP-induced hyperalgesia was related to activation of peritoneal resident cells and an increase in the release of inflammatory mediators.

PMID: 16310221 [PubMed – indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov/pubmed/16310221

[Trypsin-like proteinases and trypsin inhibitors in fruiting bodies of higher fungi]

[Article in Russian]

Gzogian LA, Proskuriakov MT, Ievleva EV, Valueva TA.

Abstract

The activity of trypsin-like proteinases and trypsin inhibitors was measured in fruiting bodies of various species of basidial fungi (Basidiomycetes). Fruiting bodies of all fungi contained these enzymes, with the exceptions of polypore (Coriolus versicolor (Fr.) Karst) and hedgehog fungus (Hericium erinaceus (Fr.) Quel), belonging to the families Polyporaceae and Hericiaceae, respectively, in which the enzyme activities were barely detectable. The activity of trypsin-like proteinases was the highest in fruiting bodies of Boletaceae and Agaricaceae. Fruiting bodies of all fungi contained trypsin inhibitors. The highest activity of trypsin inhibitors was detected in basidiomycetes of the families Boletaceae, Agaricaceae, and Pleurotaceae, including Boletus castanus (Fr.) Karst, orange-cap boletus (Leccinum aurantiacum (Fr.) Sing), and brown-cap boletus (Leccinum melanum (Fr.) Karst).

PMID: 16358748 [PubMed – indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov/pubmed/16358748

Evaluation of cytotoxic and mutagenic effects of Coriolus versicolor and Funalia trogii extracts on mammalian cells.

Unyayar A, Demirbilek M, Turkoglu M, Celik A, Mazmanci MA, Erkurt EA, Unyayar S, Cekic O, Atacag H.

Department of Environmental Engineering, Mersin University, Mersin, Turkey. aunyayar@mersin.edu.tr

Abstract

This study examined the in vitro cytotoxic activities of standardized aqueous bioactive extracts prepared from Coriolus versicolor and Funalia trogiiATCC 200800 on HeLa and fibroblast cell lines using a MTT (3-[4,5-dimetiltiazol-2-]-2-5-difeniltetrazolium bromide) cytotoxicity assay. F. trogii and C. versicolor extracts were cytotoxic to both cell lines. At 10 microL treatment level, F. trogii and C. versicolor extracts inhibited proliferation of HeLa cancer cells by 71.5% and 45%, respectively, compared with controls. Toxicity was lower toward normal fibroblasts. In the latter case, treatment at 10 microL level with F. trogii and C. versicolor extracts reduced cell proliferation by 51.3% and 38.7%, respectively. In separate experiments, the mitotic index (MI) obtained with 3 microL treatment level of unheated extracts of the two fungi was comparable to the MI value obtained by treatment with 4 microg/mL MMC (anticancer agent mitomycin-C). A significant induction of sister chromatid exchange (SCE) was observed in normal cultured lymphocytes treated with MMC (4 microg/mL). MMC treatment reduced replication index compared with treatment with unheated F. trogii extract and negative controls (p < 0.001). In contrast to MMC, F. trogii extracts did not affect the proliferation of human lymphocytes compared with controls (p > 0.05). Laccase and peroxidase enzyme activities in F. trogii extract were implicated in their inhibitory effect on cancer cells. F. trogii extract was concluded to have antitumor activity.

PMID: 16455591 [PubMed – indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov/pubmed/1645559

Identification of medicinal mushroom species based on nuclear large subunit rDNA sequences.

Lee JS, Lim MO, Cho KY, Cho JH, Chang SY, Nam DH.

Institute of Biotechnology, College of Pharmacy, Yeungnam University, Gyongsan 712-749, Republic of Korea.

Abstract

The purpose of this study was to develop molecular identification method for medical mushrooms and their preparations based on the nucleotide sequences of nuclear large subunit (LSU) rDNA. Four specimens were collected of each of the three representative medicinal mushrooms used in Korea: Ganoderma lucidum, Coriolus versicolor, and Fomes fomentarius. Fungal material used in these experiments included two different mycelial cultures and two different fruiting bodies from wild or cultivated mushrooms. The genomic DNA of mushrooms were extracted and 3 nuclear LSU rDNA fragments were amplified: set 1 for the 1.1-kb DNA fragment in the upstream region, set 2 for the 1.2-kb fragment in the middle, and set 3 for the 1.3-kb fragment downstream. The amplified gene products of nuclear large subunit rDNA from 3 different mushrooms were cloned into E. coli vector and subjected to nucleotide sequence determination. The sequence thus determined revealed that the gene sequences of the same medicinal mushroom species were more than 99.48% homologous, and the consensus sequences of 3 different medicinal mushrooms were more than 97.80% homologous. Restriction analysis revealed no useful restriction sites for 6-bp recognition enzymes for distinguishing the 3 sequences from one another, but some distinctive restriction patterns were recognized by the 4-bp recognition enzymes AccII and HhaI. This analysis was also confirmed by PCR-RFLP experiments on medicinal mushrooms.

PMID: 16554714 [PubMed – indexed for MEDLINE]Free Article

http://www.ncbi.nlm.nih.gov/pubmed/16554714

Synergic treatment for monosodium glutamate wastewater by Saccharomyces cerevisiae and Coriolus versicolor.

Jia C, Kang R, Zhang Y, Cong W, Cai Z.

State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100080, PR China.

Abstract

Biodegradation and decolorization of monosodium glutamate wastewater were carried out by using an acidophilus yeast strain of Saccharomyces cerevisiae and Coriolus versicolor. For the yeast treatment, the highest COD removal and reducing sugar removal efficiency were 76.6% and 80.2%, respectively. The color removal was only 2%. For C. versicolor treatment, the highest COD removal, color removal and reducing sugar removal efficiencies were 78.7%, 56.5% and 90.9%, respectively. The synergic treatment process, in which the yeast and C. versicolor were successively applied,exhibited great advantage over the individual process.

PMID: 16624556 [PubMed – indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov/pubmed/16624556

Polysaccharide peptides from COV-1 strain of Coriolus versicolor inhibit tolbutamide 4-hydroxylation in the rat in vitro and in vivo.

Yeung JH, Chan SL, Or PM.

Department of Pharmacology, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, NT, Hong Kong, China. johnyeung@cuhk.edu.hk

Abstract

Polysaccharide peptide (PSP), isolated from COV-1 strain of Coriolus versicolor, is commonly used as an adjunct in cancer chemotherapy in China. In this study, the effects of whole PSP extract and water extract of PSP on 4-hydroxylation of tolbutamide were investigated in rat liver microsomes in vitro and in vivo in the rat. Both the whole PSP extract and the water soluble fraction (0.5-20 microM) decreased the metabolism of tolbutamide to 4-hydroxytolbutamide in vitro. Enzyme kinetics studies showed that PSP inhibited tolbutamide 4-hydroxylase activity in a competitive, concentration-dependent manner. The whole PSP extract had a Ki value of 12.6 microM and IC50 at 18.4 microM, while the water extract had a Ki value of 6.9 microM and IC50 at 9.8 microM. Sulphaphenazole, a specific human CYP2C9 inhibitor, showed a Ki value of 30.8 microM and IC50 at 44.0 microM in the test system. In the pharmacokinetic studies in vivo, acute PSP (4 micromol/kg, i.p.) treatment did not produce significant changes in tolbutamide clearance, but produced a decrease in the Cinitial (7.4%) and an increase in the Vd (7.4%). Sub-chronic pre-treatment of PSP (1-2 micromol/kg/day, i.p.) for three days did not affect the clearance and AUC of tolbutamide, but the Cinitial was decreased, together with increases in the T1/2, and Vd. The formation of 4-hydroxytolbutamide in vivo was decreased in both acute and sub-chronic studies. Taken together, this study demonstrated the PSP can inhibit tolbutamide 4-hydroxylation both in vitro and in vivo. Despite the fact that CYP isoforms that metabolise tolbutamide are different between rat and human liver due to different catalytic characteristics, and rat studies may not be directly extrapolatable to man, the concomitant use of PSP with other CYP2C substrates should be carefully monitored.

PMID: 16698161 [PubMed – indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov/pubmed/16698161

Modulation of antipyrine clearance by polysaccharide peptide (PSP) isolated from Coriolus versicolor in the rat.

Chan SL, Yeung JH.

Department of Pharmacology, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong SAR, China.

Abstract

Polysaccharide peptide (PSP), isolated from Coriolus versicolor COV-1, has been previously shown to have immuno-stimulatory, anti-tumour and analgesic effects in animal models. When used as an adjunct in cancer chemotherapy in clinical trials carried out in China, PSP improved the quality of life in the patients by improving appetite and alleviating symptoms associated with cancer chemotherapy. In this study, the effects of non-toxic doses of PSP on phase I metabolism was investigated in the rat, using the conventional probe antipyrine. Acute PSP (3-5 micromol/kg, i.p.) treatment did not produce significant changes in antipyrine clearance. Sub-chronic treatment with PSP (1-3 micromol/kg/day, i.p., 3 days) decreased the antipyrine clearance (30-35%), with an increase in the plasma half-life (T1/2) by 55% and an increase in the area under concentration-time curve (AUC) by 61%. Total hepatic cytochrome P450 (P450) was dose-dependently decreased (32-54%) after sub-chronic, but not the acute treatment of PSP. Given that PSP can affect phase I metabolism and hepatic cytochrome P450 content, the concomitant use of PSP with other therapeutic agents that undergo phase I metabolism should be carefully monitored.

PMID: 16698162 [PubMed – indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov/pubmed/16698162

The production of extracellular mucilaginous material (ECMM) in two wood-rotting basidiomycetes is affected by growth conditions.

Vesentini D, Dickinson DJ, Murphy RJ.

Department of Biological Sciences, Imperial College London, UK. damiano.vesentini@ensisjv.com

Abstract

The ability of two wood-decay basidiomycetes to produce extracellular mucilaginous material (ECMM) and its relationship with total biomass production has been investigated. Growth and ECMM production by the white-rot fungus Coriolus versicolor and the brown-rot fungus Gloeophyllum trabeum were assessed in liquid culture under different nutritional and environmental conditions. Nutritional, pH and temperature factors all influenced significantly the proportion of ECMM in the total biomass produced. When total biomass production was reduced due to unfavorable growth conditions (stress), the proportion of ECMM in the biomass was elevated. The results are discussed with regard to the possible role(s) of ECMM in the responses of these fungi to stress.

PMID: 16722210 [PubMed – indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov/pubmed/16722210

Effects of VPS extract of Coriolus versicolor on cancer of the large intestine using a serial sacrifice technique.

Toth B, Coles M, Lynch J.

The Eppley Institute for Research in Cancer and Allied Diseases and Department of Preventive and Societal Medicine, University of Nebraska Medical Center, Omaha, Nebraska 68198, USA. btoth@unmc.edu

Abstract

VPS, a hot water extract of the Coriolus versicolor mushroom, was given at a 2% dose level in the diet of female Swiss Webster CFW outbred mice in a serial sacrifice experiment. The mice were also administered either 1,2-dimethylhydrazine dihydrochloride (1,2-DMH) as ten weekly subcutaneous (s.c) injections of 20 microg/g body weight or physiological saline (PS) as ten weekly (s.c) injections of 0.01 ml/g body weight. The animals were sacrificed at 26 weeks or 35 weeks after the first injection of 1,2-DMH or PS. The number of mice with large intestinal tumors and the total number of these tumors were: Group I (1,2-DMH), 29 and 438; Group 2 (VPS + 1,2-DMH), 29 and 344; Group 3 (VPS + PS), 0 and 0; and Group 4 (PS), I and 1, in the mice sacrificed at 26 weeks. The corresponding tumor incidences in mice sacrificed at 35 weeks were: Group 1 (1,2-DMH), 30 and 323; Group 2 (VPS + 1,2-DMH), 29 and 521; Group 3 (VPS + PS), 1 and 2; and Group 4 (PS), 0 and 0. Histopathologically, the tumors were diagnosed as polypoid adenomas and adenocarcinomas of the cecum, colon and rectum. Contrary to expectations, the VPS treatment enhanced the development of large intestinal tumors induced by 1,2-DMH in animals sacrificed at 35 weeks after the first injection of the carcinogen.

PMID: 16724667 [PubMed – indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov/pubmed/16724667