Department of Zoology, The University of Hong Kong, Pokfalum Road, Hong Kong, SAR, P.R. China.
The polysaccharide peptide (PSP) isolated from the mycelia of Chinese Medicinal fungus Coriolus versicolor has proven benefits in clinical trials in China but the mechanism of action has not been elucidated. In this study, HL-60 cell line was used to investigate the anti-proliferation and cell death process of PSP. The cytotoxicity of PSP on normal human T-lymphocytes was also evaluated. We show that PSP induced apoptosis of human promyelocytic leukemia HL-60 cells but not of normal human T-lymphocytes. The apoptotic machinery induced by PSP was associated with a decrease in Bcl-2/Bax ratio, drop in mitochondrial transmembrane potential, cytochrome c release, and activation of caspase-3, -8 and -9. Activation of the cellular apoptotic program is a current strategy for the treatment of human cancer, and the selectivity of PSP to induce apoptosis in cancerous and not on normal cells supports its development as a novel anticancer agent.
L.Z. Xu Laboratory of Pathology Cancer Institute, Shanghai Medical University
Abstract
In the present study the anti-cancer effect of polysaccharide peptide of Coriolus versicolor Cov-1 (PSP) was compared with polysaccharide peptide of Coriolus versicolor CM-101 (PSK) on four human tumor cell line targets (SGC 7901, stomach cancer cell; SPC, human lung adenocarcinoma cell; SLY, human monocytic leukemia cell and Mei, human skin histiocytic lymphoma cell) in Vitro.
PSP had similar cytotoxic effects upon human tumor cells as PSK, both inhibiting cell growth. In comparison with control specimens, the SPC cell line treated with PSP (1000ug/ml) for 72 hours at 37oC showed marked morphological changes such as cell swelling, chromatin aggregation, formation of polynuclear cells and sawtooth on the surface of cell nuclei.
PSK as a new immunomodulative drug had been widely used for clinical anticancer therapy in Japan. When combined with chemotherapy, radiotherapy and surgical operation, PSK is found to be able to improve the therapeutic effects. In 1983, a polysaccharide peptide of Coriolus versicolor Cov-1 was isolated from the mycelia by Qing-yao Yang. It is possessed of physio-chemical characteristics similar to PSK and designated as PSP. In the present study the anti-cancer effect of PSP was compared with PSK using four human tumor cell line targets in vitro.
Department of Physiology, Faculty of Medicine, University of Hong Kong, Hong Kong.
Coriolus versicolor polysaccharide peptide (CVP) and the bis-benzylisoquinoline alkaloids, tetrandrine (TET) and berbamine (BER), the active ingredients isolated from Chinese medicinal herbs known to possess antitumor activities, concentration-dependently inhibited the proliferation of human leukemic HL-60 cells. CVP did not affect the growth of normal human peripheral blood lymphocytes (PBL), whereas TET elicited concentration-dependent cytotoxic effects. Morphological observation and DNA analysis revealed that CVP elicited no effect on the morphological features of HL-60 cells and did not cause DNA fragmentation, but TET and BER caused cell shrinkage with the formation of apoptotic bodies, and showed clear evidence of DNA fragmentation. These findings indicate that TET and BER, but not CVP, inhibited the proliferation of HL-60 cells via induction of apoptosis.
(NAPSI)-The immune system is the body’s ultimate defense against illness and disease. A healthy immune system helps defend the body against the common cold to the most catastrophic illness that you may face.
Boosting your immune system can be easier than you might imagine.
One way is to take supplements and one supplement growing in popularity involves mushrooms. WebMD states that the Coriolus mushroom is used to stimulate the immune system and increase energy.
Traditionally, the Coriolus Versicolor mushroom has been used in China for several thousands of years because of its immune- boosting capabilities.
Its documented usage in history dates back to the mid-1300s during the Ming dynasty. In the 1970s, researchers in Japan started experimenting with the mushroom by extracting its essence in the form of polysaccharide krestin (PSK) and as a polysaccharide peptide (PSP) in China.
Human clinical trials show that the active ingredient in these mushrooms can maintain health and wellness.
There have been over 400 animal and human studies worldwide and in the U.S., including over a dozen human-based placebo trials.
inLife offers Coriolus Versicolor as a daily dietary supplement in pill form to help maintain and stimulate the body’s immune system. It’s available as inForce Immune Builder, a combination of PSK and PSP.
inForce offers much-needed immune-building assistance and it can be taken on a daily basis. inForce is made in the U.S.A. in a cGMP-certified facility and is also vegan friendly.
More information can be found by visiting www.buyinforce.com.
Department of Anatomy, Faculty of Medicine, Chinese University of Hong Kong, Shatin.
Abstract
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.
Department of Pharmacology, Faculty of Medicine, Chinese University of Hong Kong.
Abstract
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.
Department of Biology, Chinese University of Hong Kong, Shatin.
Abstract
A polysaccharide-peptide complex (PSPC) with immunomodulatory and antitumor activities was obtained from a submerged mycelial culture of Tricholoma sp., a local edible mushroom. The polysaccharide-peptide complex exhibited a molecular weight of 17 K in gel filtration and a single band after SDS-polyacrylamide gel electrophoresis. It was characterized by non-adsorption on both DEAE-Sepharose CL-6B and CM-cellulose. It could activate the macrophages, stimulate the proliferation of T-cells, and inhibit the growth of sarcoma 180 in mice. It possessed more potent immunomodulatory and antitumor activities than Coriolus versicolor polysaccharopeptide (PSP) and deserves to be studied as a potential agent for immunomodulation and cancer therapy.
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.
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.
Department of Radiation Medicine, Loma Linda University/Independent Order of Foresters Cancer Research Laboratory, CA 92350, USA.
Abstract
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.