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Polysaccharopeptide from the Turkey Tail Fungus Trametes versicolor (L.:Fr.) Pilát Inhibits Human Immunodeficiency Virus Type 1 Reverse Transciptase and Protease
Abstract
Polysaccharopeptide from the Turkey Tail fungus Trametes (=Coriolus) versicolor has been reported to possess a number of important attributes including anticancer, immunomodulatory, analgesic, and hepatoprotective activities. In this investigation, it is shown that the polysaccharopeptide is capable of inhibiting human immunodeficiency virus type 1 (HIV-1) reverse transcriptase and protease, the two enzymes of paramount importance to the life cycle of the HIV. The polysaccharopeptide inhibits other proteases including trypsin, α-chymotrypsin, proteinase K, subtilisin, and elastase to a smaller extent. The anti-HIV enzyme and immunostimulatory activities of the mushroom polysaccharopeptide make it a potential candidate for the therapy of AIDS.
... In contrast, Liu et al. revealed that PSK can inhibit the growth of B cells and activate natural killer cells and T cells in EBV (Epstein-Barr virus)-infected blood lymphocytes of the umbilical cord and exert increased cytotoxicity against B cells infected with EBV [57]. Furthermore, Ng et al. reported that, in a clinical trial, the food additive of the mushrooms reduced the frequency and inhibited the effect of the HSV-2 virus in pregnant women completely [58]. ...
It is well known that the utilization of mushrooms as therapeutic agents is not new. Over the past years, they are used by the local individuals as food as well as medicines, throughout the world. Nowadays, mushrooms are excessively used in medicine, pharmacy, food, and fermentation fields, as well. Wild mushrooms are of particular interest, especially Trametes versicolor (commonly known as turkey mushrooms) due to their various uses in the food and pharmaceutical industries. They represent not only a huge storehouse of vitamins, minerals, and dietary fiber, but they are also an important source of bioactive polysaccharides. They are widely used in traditional oriental therapies. The fruiting bodies are used in the preparation of health tonics and tea. The present review is necessary to explore more about this mushroom-like classical taxonomy, morphology, nutritional value, bioactivity, various health attributes, mechanism of bioactive components against various diseases, and food applications. The influence of processing processes on the nutritional properties and bioactivity of the fungus is discussed. Potential bioactive components, promising health attributes of Trametes versicolor have been extensively described. Besides, several in vivo and in vitro studies have demonstrated beneficial effects of polysaccharopeptides (PSP) and Polysaccharide-K (PSK) on aspects related to immune function and inflammation, also presenting an anti-cancerous effect. Moreover, PSP and PSK were successfully described to decrease several life-threatening diseases. Potential food applications of Trametes versicolor were detailed to signify the effective utilization of the mushroom in functional food formulation.
... Coriolus versicolor is a distinguished medicinal mushroom, owning functions on anti-age, immunoregulation (13), treating multiple hepatitis (4), inhibiting diverse cancer cells proliferation (7,8,10). It also has a certain efficacy on decreasing toxic actions and side effects from chemotherapeutic drugs, and treating AIDS (15,16). At present, C. versicolor polysaccharide is used widely to cure hepatitis, and glycoprotein from its mycelia has been employed as an anticancer drug in Japan for decades. ...
The study was conducted to evaluate effect of Coriolus versicolor mycelia on degrading starch and improving nutrition value in corn grits through solid state fermentation technique. The results showed that using soybean meal as a nitrogen source, α-amylase secreted from C. versicolor expressed 407.25U/g of activity, leading to 45.15% of starch degraded. The activity grew with fermentation time until the 15th day, after that the amylase was deactivated rapidly. An orthogonal experiment designed for the study illustrated that degradation rate of starch in corn grits attained to maximum, 50.51%, when 100g of corn grits, added 16g of soybean meal, were fermented by C. versicolor for 12 days, in an initial pH 5.5. After fermenting, compared to the nonfermented control, contents of amino acids, total sugar, crude fat and crude protein were increased by 21.00%, 38.45%, 55.56%, 69.15% respectively. The significant improvement of nutrition value in corn grits is probably attributed to the intense metabolism of C. versicolor.
... An A. blazei extract (with a high ratio of betaglucan) inhibited cell proliferation in both androgen-dependent and androgen-independent prostate cancer cell lines via an apoptotic pathway, with activities of caspase 3 and DNA fragmentation being enhanced the most in androgenindependent PC3 cells (Yu et al., 2009a). Beta-glucan from Grifola frondosa (Maitake) has a cytotoxic effect on human androgen-independent prostatic cancer PC-3 cells in vitro, leading to apoptosis (Fullerton et al., 2000), while a recent study has also suggested that a Phellinus linteus extract is able to sensitize advanced prostate cancer cells to apoptosis in athymic nude mice (Tsuji et al., 2010). ...
... Fruiting bodies have been the object of most studies of the antiviral activity of Basidiomycetes (Takehara M, et al., 1979;Amoros M, et al., 1997;El-Mekkawy S., et al., 1998;Eo S-K, et al., 1999;Pirano F, et al., 1999;Wang H X, et al., 2000;Oh K.-W, et al., 2000;Awardh A N A, et al., 2003;Mothana R A A, et al., 2003;Ngai P H K, et al., 2003;Stamets P, 2005;Bruggemann R, et al., 2006;Ohta Y, et al., 2007;Faccin L C, et al., 2007;Gu C Q, et al., 2007;Lv H, et al., 2009;Kabanov A S, et al., 2011;Ibragimova Zh B, et al., 2012;Vlasenko V A, et al., 2012;Fillipova E I, et al., 2012Fillipova E I, et al., , 2013Kostina N E, et al., 2013). However, the vegetative mycelium of these mushrooms is not inferior to fruit bodies in terms of the content of antiviral active substances (Hirose K, et al., 1987;Eo S-K, et al., 2000;Liu J, et al., 2004;Ng T B, et al., 2006;Cardozo F T G S, et al., 2011;Prozenko M A, et al., 2012;Teplyakova T V, et al., 2012) and has a number of advantages in the cultivation process. Vegetative mycelium has a constant qualitative and quantitative composition, and its cultivation requires much less time and significantly less energy. ...
In this study, we investigated the in vitro antiviral activity of the mycelia of higher mushrooms against influenza virus type A (serotype H1N1) and herpes simplex virus type 2 (HSV-2), strain BH. All 10 investigated mushroom species inhibited the reproduction of influenza virus strain A/FM/1/47 (H1N1) in MDCK cells reducing the infectious titer by 2.0–6.0 lg ID50. Four species, Pleurotus
ostreatus, Fomes fomentarius, Auriporia aurea, and Trametes versicolor, were also determined to be effective against HSV-2 strain BH in RK-13 cells, with similar levels of inhibition as for influenza. For some of the investigated mushroom species—Pleurotus eryngii, Lyophyllum shimeji, and Flammulina velutipes—this is the first report of an anti-influenza effect. This study also reports the first data on the medicinal properties of A. aurea, including anti-influenza and antiherpetic activities. T. versicolor 353 mycelium was found to have a high therapeutic index (324.67), and may be a promising material for the pharmaceutical industry as an anti-influenza and antiherpetic agent with low toxicity. Mycelia with antiviral activity were obtained in our investigation by bioconversion of agricultural wastes (amaranth flour after CO2 extraction), which would reduce the cost of the final product and solve some ecological problems.
... It was shown that PSP and PSK are very effective in the treatment of different cancer types including gastric, lung, nasopharyngeal, colorectal, breast, oesophageal as well as uterine cancer (Tsukagoshi et al. 1984, Ng 1998, Parris 2000, Fisher and Yang 2002, Cui and Chisti 2003, Kanazawa et al. 2005, Jimenez-Medina et al. 2008, Standish et al. 2008. T. versi color also shows strong anti-viral activities proven in vitro , Hobbs 2004, Mlinaric et al. 2005, Ng et al. 2006 and also on HIV patients (Pfeiffer 2001). T. versicolor polysaccharides and polysaccharopeptides besides anti-cancer possess also immune system enhancing activities (Tzianabos 2000, Standish et al. 2008). ...
Abstract:
Slovenia with its diverse environment is home to more than 2400 fungal
species out of which especially many macromycetes have for millennia been used
worldwide as natural remedies. These species of mushrooms were in the past picked
from the nature, but today can be cultivated as fruiting bodies or fungal biomass on
different substrates. They possess immunomodulating, antiviral, antibacterial and
anticancer activities and can be used against allergies, dementia, Alzheimer disease
and in many other diseases. They represent a vast potential as natural remedies with
no or very little adverse effects and can be processed into food supplement or further
developed into medicines. These mushrooms are a natural treasure, which enables
us to be more self-sufficient if we cultivate them for medical and certain species for
nutritional purposes as well.
... Coriolus versicolor is a distinguished medicinal mushroom, owning functions on anti-age, immunoregulation (13), treating multiple hepatitis (4), inhibiting diverse cancer cells proliferation (7,8,10). It also has a certain efficacy on decreasing toxic actions and side effects from chemotherapeutic drugs, and treating AIDS (15,16). At present, C. versicolor polysaccharide is used widely to cure hepatitis, and glycoprotein from its mycelia has been employed as an anticancer drug in Japan for decades. ...
The study was conducted to evaluate effect of Coriolus versicolor mycelia on degrading starch and improving nutrition value in corn grits through solid state fermentation technique. The results showed that using soybean meal as a nitrogen source, α-amylase secreted from C. versicolor expressed 407.25U/g of activity, leading to 45.15% of starch degraded. The activity grew with fermentation time until the 15(th) day, after that the amylase was deactivated rapidly. An orthogonal experiment designed for the study illustrated that degradation rate of starch in corn grits attained to maximum, 50.51%, when 100g of corn grits, added 16g of soybean meal, were fermented by C. versicolor for 12 days, in an initial pH 5.5. After fermenting, compared to the nonfermented control, contents of amino acids, total sugar, crude fat and crude protein were increased by 21.00%, 38.45%, 55.56%, 69.15% respectively. The significant improvement of nutrition value in corn grits is probably attributed to the intense metabolism of C. versicolor.
The feline immunodeficiency virus (FIV) is a widespread lentivirus of felids. Due to its worldwide diffusion and the lack of an effective preventive and therapeutic protocol, it has a high impact on the cats’ health. Several therapeutical protocols have been proposed, among those, phytotherapeutic compounds have been tested with the purpose to find a possible natural treatment. The most studied active compounds are derived from Ganoderma lucidum, Cordyceps sinensis, and Trametes versicolor. The present study aims to investigate in vitro antiviral effects of a commercially available compound HELP-TH1 (Camon, S.p.A., Italy) against FIV. The antiviral effect of HELP-TH1 was evaluated by quantifying and comparing the viral load of control groups, infected and not-treated cells, vs both experimental groups, infected and treated cells. Our data indicate that HELP-TH1 reduce the viral load in the experimental conditions demonstrating its antiviral effect.
The effect of polysaccharide peptides from Coriolous versicolor (PSP) on peripheral blood counts was evaluated on eleven Chinese breast cancer patients. There was no significant drop in their peripheral white blood counts and platelet counts after three cycles of chemotherapy. Half of the studied patients noticed an increase in appetite. The authors concluded that PSP may be a useful adjunctive treatment during chemotherapy.
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.
An aqueous extract from the marine red alga, Schizymenia pacifica has been tested in a cell free system for its effect on reverse transcriptase from avian retrovirus (avian myeloblastosis virus), and mammalian retrovirus (Rauscher murine leukemia virus). The extract inhibited reverse transcriptase from both these retroviruses but showed almost no effect, if any, on the activity of cellular DNA polymerase alpha and RNA polymerase II in vitro. Consequently it is unlikely to have an adverse effect on the growth of cultured cell. The inhibitory activity of the extract was stable over a relatively wide pH range (pH 1-11) and was not lost after pronase digestion. Inhibitory activity of the extract was lost after boiling at 100 degrees C in 0.67 N HCl, and after treatment with 100 mM NaIO4. The active principle in the extract has an apparent molecular weight in excess of 100,000 daltons. This new reverse transcriptase inhibitor is probably a polysaccharide.
The dimethylsulfoxide extract of the Chinese medicinal herb Viola yedoensis demonstrates high inhibitory activity toward HIV-1 in vitro. The corresponding methanol extract also showed inhibitory activity but not as high as the dimethylsulfoxide extract. Anti-HIV activity in the extracts is accompanied by cytotoxicity, and we describe here the separation of the cytotoxic material from the active fraction. We also describe the procedure for isolation, purification, and separation of the active component from crude extracts of V. yedoensis as well as details of its activity against HIV-1. The UV-visible, infrared (IR) and proton nuclear magnetic resonance (NMR) data and certain other characteristics of the active compound are also presented. Initial chemical tests and the proton NMR and IR spectra indicate a high molecular weight sulphonated carbohydrate polymer, and chromatographic evidence suggests an MW between 10,000 and 15,000.
The protective effects of polysaccharide peptide (PSP), isolated from Coriolus versicolor COV-1, on paracetamol-induced hepatotoxicity was investigated in this study. The effect of PSP on hepatic glutathione status was also studied. PSP (300 mg/kg, i.p.) caused a 40% depletion of hepatic reduced glutathione (GSH) with a concomitant 50% increase in oxidized glutathione (GSSG), thus producing a 3-fold increase in the GSSG/GSH ratio. The PSP-induced GSH depletion itself had no hepatotoxic effects. PSP protected against paracetamol-induced hepatotoxicity by decreasing the paracetamol-induced elevation of serum glutamic-pyruvic transaminase (SGPT) activity from 511 +/- 71 U/ml to 187 +/- 58 U/ml (controls without paracetamol 105 +/- 4 U/ml) and serum glutamic-oxaloacetic transaminase (SGOT) activity from 462 +/- 63 to 152 +/- 48 U/ml (controls without paracetamol 54 +/- 6 U/ml). PSP did not reverse the depletion of total glutathione (GSH+GSSG) by the toxic dose of paracetamol. The GSSG/GSH ratio, which is a measure of oxidative stress, was significantly (p < 0.05) decreased when PSP was coadministered with paracetamol. PSP dose-dependently decreased the covalent binding of [14C]-paracetamol to microsomal proteins in vitro. When PSP was given to rats subchronically for 7 days (300 mg/kg/day, i.p.), the subsequent microsomes obtained also showed a 25% decrease in covalent binding to [14C]-paracetamol, suggesting that PSP interacted with the microsomal proteins rather than the chemically reactive metabolite of paracetamol. The changes in the binding affinity and capacity of the microsomal proteins by PSP may be related to its ability to alter the redox potential as indicated by the effects of PSP on the GSSG/GSH status.
Polysaccharopeptide (PSP) is a substance produced by an edible mushroom, Coriolus versicolor which has been claimed to possess antitumor activity. However, neither tumoricidal activity nor cytotoxicity was observed when five tumor cell lines and mouse peritoneal macrophages were cultured in vitro in the presence of 2.5-10 micrograms/ml PSP. An increase in the production of reactive nitrogen intermediates, reactive oxygen intermediates (superoxide anions) and tumor necrosis factor was measured in peritoneal macrophages collected from inbred C57 mice which had received PSP in the drinking water for 2 weeks. Northern blot analysis also demonstrated that PSP activated the transcription of tumor necrosis factor gene in these cells, indicating that PSP exerted an immunomodulatory effect on the defensive cells.
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.
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.
The nervous mechanism of the immune potentiating effect of Coriolus versicolor polysaccharides peptides (PSP) was studied in Wistar rats.
The unit discharge of the mediobasal hypothalamus (MBH) neurons was recorded extracellularly and the lymphocyte proliferation was measured.
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.
MBH is involved in the immune-potentiating effect of PSP.
To study the role of interleukin-2 (IL-2) and mediobasal hypothalamus (MBH) in analgesia produced by Coriolus versicolor polysaccharide peptide (PSP).
The IL-2 antiserum was injected i.c.v. or i.p. and the MBH was destroyed electrolytically.
PSP i.g. 1 g.kg-1.d-1 for 6 d increased the pain threshold in tail stimulation-vocalization test in rats. This PSP-produced analgesia was blocked by i.c.v., but not i.p., IL-2 antiserum and disappeared after electrolytic lesion of MBH.
The analgesia produced by PSP is mediated by IL-2 which is activated by PSP and interacts with IL-2 receptors in the MBH.
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.