Immune Fx
References and Research Articles
CORIOLUS VERSICOLOR
Br J Biomed Sci 2000; 57(2):130-6
Effect of polysaccharide krestin on glutathione peroxidase gene expression in mouse peritoneal
macrophages.
Pang ZJ, Chen Y, Zhou M, Wan J, Research Laboratory of Free Radical Medicine, First Military
Medical University, Guangzhou, People's Republic of China.
Pe Polysaccharide krestin (PSK) is a protein-bound polysaccharide extracted from the sporophore
Coriolus versicolor. Previously, we found that PSK could reduce the oxidative injury that
oxidised low-density lipoprotein (Ox-LDL) produced in monocytes/macrophages, and therefore
have some pro-phylactic or therapeutic effect on atherosclerosis. Glutathione peroxidases,
including selenium-dependent glutathione peroxidase (SeGPx) and non-selenium-dependent glutathione
peroxidase (non-SeGPx, also called glutathione S-transferase [GST]), play an important role
in the defence against oxidative injury. In order to find out if the effects of PSK were
associated with antioxidant enzymes, we investigated its effect on glutathione peroxidase
activity and messenger RNA (mRNA) expression in mouse peritoneal macrophages. Results showed
that PSK enhanced SeGPx and non-SeGPx activity, and increased SeGPx and GST-P (pi class
GST) mRNA in mouse peritoneal macrophages. In addition, the induction by PSK of the two
glutathione peroxidases could be blocked by cycloheximide (30 micrograms/mL), but 5 micrograms/mL
actinomycin D and 50 micrograms/mL acetovanilone (a superoxide inhibitor) had no effect.
We conclude that PSK improved glutathione peroxidase activity through transcriptional induction
of mRNA expression.
PMID: 10912287, UI: 20369988
Cancer Biother Radiopharm 1996 Dec;11(6):393-403
Immunotherapy with low-dose interleukin-2 and a polysaccharopeptide derived from Coriolus
versicolor.
Mao XW, Archambeau JO, Gridley DS, Department of Radiation Medicine, Loma Linda University/Independent
Order of Foresters Cancer Research Laboratory, CA 92350, USA.
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. PMID: 10851500, UI: 20310049
Altern Med Rev 2000 Feb; 5(1):4-27
The use of mushroom glucans and proteoglycans in cancer treatment.
PM Kidd
Immunoceuticals can be considered as substances having immunotherapeutic efficacy when
taken orally. More than 50 mushroom species have yielded potential immunoceuticals that
exhibit anticancer activity in vitro or in animal models and of these, six have been investigated
in human cancers. All are non-toxic and very well tolerated. Lentinan and schizophyllan
have little oral activity. Active Hexose Correlated Compound (AHCC) is poorly defined but
has shown early clinical promise. Maitake D-Fraction has limited proof of clinical efficacy
to date, but controlled research is underway. Two proteoglycans from Coriolus versicolor
- PSK (Polysaccharide-K) and PSP (Polysaccharide-Peptide - have demonstrated the most promise.
In Japanese trials since 1970, PSK significantly extended survival at five years or beyond
in cancers of the stomach, colon-rectum, esophagus, nasopharynx, and lung (non-small cell
types), and in a HLA B40-positive breast cancer subset. PSP was subjected to Phase II and
Phase III trials in China. In double-blind trials, PSP significantly extended five-year
survival in esophageal cancer. PSP significantly improved quality of life, provided substantial
pain relief, and enhanced immune status in 70-97 percent of patients with cancers of the
stomach, esophagus, lung, ovary, and cervix. PSK and PSP boosted immune cell production,
ameliorated chemotherapy symptoms, and enhanced tumor infiltration by dendritic and cytotoxic
T-cells. Their extremely high tolerability, proven benefits to survival and quality of life,
and compatibility with chemotherapy and radiation therapy makes them well suited for cancer
management regimens. Publication Types: Review, tutorial, PMID: 10696116, UI: 20161032
Chung Kuo Yao Li Hsueh Pao 1998 Jan;19(1):67-70
Involvement of interleukin-2 in analgesia produced by Coriolus versicolor polysaccharide
peptides.
Gong S, Zhang HQ, Yin WP, Yin QZ, Zhang Y, Gu ZL, Qian ZM, Tang PL, Laboratory of Neurobiology,
Suzhou Medical College, China.
AIM: To study the role of interleukin-2 (IL-2) and mediobasal hypothalamus (MBH) in analgesia
produced by Coriolus versicolor polysaccharide peptide (PSP). METHODS: The IL-2 antiserum
was injected i.c.v. or i.p. and the MBH was destroyed electrolytically. RESULTS:
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. CONCLUSION: The analgesia produced by
PSP is mediated by IL-2 which is activated by PSP and interacts with IL-2 receptors in the
MBH.
PMID: 10375763, UI: 99304051
Chung Kuo Yao Li Hsueh Pao 1996 May;17(3):271-4
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.
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, UI: 99029299
Chung Kuo Yao Li Hsueh Pao 1996 Mar; 17(2):102-4
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.
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, UI: 98445830
Int J Immunopharmacol 1998 Apr-May; 20(4-5):125-39
Immunopharmacologic agents in the amelioration of hepatic injuries.
Farghali H, Masek K, Institute of Pharmacology, First Faculty of Medicine, Charles University,
Prague, Czech Republic.
A number of immunomodulating agents of different origin have been shown to reduce liver
injury of various etiologies. Immunostimulants like levamisole, BCG, a protein polysaccharide
from myceria Coriolus vesicolor PS-K, a streptoccocal preparation OK-432 and immunomodulators
like N-acetylmuramyl-L-alanyl-D-isoglutamine (MDP) and its analogs. Selective T-cell suppressors
like the polypeptide cyclosporine A (CsA) and the macrolide FK 506 (tacrolimus) have also
been claimed to possess hepatoprotrophic or hepatoprotective properties at low doses. The
aim of this review article is to highlight the interplay between the administration of immunomodulating
agents and the amelioration of hepatic injuries. Hepatic effects of exogenous immunomodulators
are discussed with special focus on the most widely used immunosuppressive agents, CsA and
tacrolimus. An important question exists as to whether these potential hepatoprotective
effects are related mechanistically to the immune system or are working at different levels.
Due to the differences in effects and modes of actions of various immunoactive substances
presented herein, a common mechanism for their cytoprotective effects cannot be formulated
at this stage. Levamisole and cyanidanol may protect cells against necrosis by acting as
free radical scavengers. MDP and its analogs reduce carbon tetrachloride-elevated (CCl4)
lipid peroxides and their protective effects are primarily on hepatic cytoplasmic membranes
where lipid peroxidation and calcium homeostasis interact. MDP reduced CCl4-elevated calcium
in both intact hepatocytes and in the post microsomal supernatant suggest that the influx
of extracellular calcium across plasma membrane is affected. Elevations of intracellular
calcium above a threshold are involved in: the stimulation of Ca2+-sensitive enzymes such
as phospholipase A2, endonucleases and proteases, the conversion of xanthine dehydrogenase
to xanthine oxidase and the formation of free radicals, all of which disturb biomembranes.
MDP and its analogs, in a specific dose range, may act to maintain intracellular calcium
within physiological ranges. Highly complex cellular signalling systems, including calcium,
are involved in the explanation of the mechanism of the immunosuppressive effect of CsA
and tacrolimus. The hepatoprotective effects of these selective immunosuppressive agents,
however, are independent of the inhibition of T-cell activation. The cyclophilin and tacrolimus
binding proteins of the mitochondria are the receptors for these compounds and play a key
role in the regulation of mitochondrial permeability transition pores. CsA or tacrolimus
inhibition of mitochondrial permeability transition pores does not require interaction with
calcineurin, indicating a disassociation between immunosuppression and mitochondrial protection.
The involvement of intracellular or intramitochondrial proteins in the modulation of mitochondrial
permeability transition pores with the creation of a partially impermeable state for Ca2+
movement in drug-treated mitochondria and the dissociation of this effect from immunomodulatory
actions potentially offers new and promising approaches for the development of new pharmacologicals
targeted at therapeutic intervention. Clinical trials of these drugs as hepatoprotective
agents are limited. Use of CsA in patients with primary biliary cirrhosis and autoimmune
chronic hepatitis and in cirrhotic animal models produced by chronic administration of CCl4
have yielded encouraging results. It seems that this class of compounds may be of substantial
benefit in liver protection against many pathological conditions where disturbance in mitochondrial
function and in Ca2+ homeostasis appear to be prerequisites for cell injury. Publication
Types: Review, tutorial
Gen Pharmacol 1998 Jan; 30(1):1-4
A review of research on the protein-bound polysaccharide (polysaccharopeptide, PSP) from
the mushroom Coriolus versicolor (Basidiomycetes: Polyporaceae).
Ng TB, Department of Biochemistry, Faculty of Medicine, Chinese University of Hong Kong,
Shatin, N.T., Hong Kong.
1. Protein-bound polysaccharides, designated as PSK and PSP, have been isolated from the
CM-101 strain and the COV-1 strain, respectively, of the mushroom Coriolus versicolor. This
article aims at summarizing existing research findings about PSP since information on PSK
is well documented. 2. PSP possesses a molecular weight of approximately 100 kDa. Glutamic
and aspartic acids are abundant in its polypeptide component, whereas its polysaccharide
component is made up of monosaccharides with alpha-1,4 and beta-1,3 glucosidic linkages.
The presence of fucose in PSK and rhamnose and arabinose in PSP distinguishes the two protein-bound
polysaccharides, which are otherwise chemically similar. 3. PSP is classified as a biological
response modifier. It induces, in experimental animals, increased gamma-interferon production,
interleukin-2 production, and T-cell proliferation. It also counteracts the depressive
effect of cyclophosphamide on white blood cell count, interleukin-2 production and delayed-type
hypersensitivity reaction. Its antiproliferative activity against tumor cell lines and
in vivo antitumor activity have been demonstrated. A small peptide with a molecular weight
of 16-18 kDa originating from PSP has been produced with antiproliferative and antitumor
activities. 4. PSP administered to patients with esophageal cancer, gastric cancer and
lung cancer, and who are undergoing radiotherapy or chemotherapy, helps alleviate symptoms
and prevents the decline in immune status.
Publication Types: Review, tutorial, PMID: 9457474, UI: 98118800
Oncology 1997 Sep-Oct; 54(5):414-23
Effects of OK-432 (picibanil) on the estrogen receptors of MCF-7 cells and potentiation
of antiproliferative effects of tamoxifen in combination with OK-432.
Aoyagi H, Iino Y, Takeo T, Horii Y, Morishita Y, Horiuchi R, Second Department of Surgery,
Gunma University School of Medicine, Maebashi, Japan.
OK-432 (picibanil), a streptococcal preparation, has a strong biological response modifier
(BRM) function and is expected to produce clinical improvement and prolongation of survival
in treated cancer patients in Japan. We were interested in whether OK-432 augments estrogen
receptor (ER) levels in breast cancer. To investigate the effect of the BRMs on cellular
growth and the characteristics of ER and progesterone receptors (PgR) in the human breast
cancer cell line MCF-7, we used OK-432, Krestin (PSK), a protein-bound polysaccharide extracted
from Coriolus versicolor, and lentinan, a fungal branched (1...3)-beta-D-glycan. OK432
and PSK dose dependently inhibited DNA synthesis of MCF-7 cells, and the 50% inhibitory
concentrations of OK-432 and PSK were 1.2 KE (klinische Einheit, clinical unit)/ml and
200 micrograms/ml, respectively. Lentinan showed no direct anticancer effect in vitro.
We found that OK-432 induced a 2-fold increase in ER levels in MCF-7 cells at 0.005 KE/ml,
but not in PgR. Lentinan and low-dose PSK did not change ER or PgR levels, but high-dose
PSK decreased ER and PgR. We also studied the combined effect of OK-432 and antiestrogens,
tamoxifen (TAM) and DP-TAT-59. The combined treatment with OK-432 and TAM showed an additive
inhibitory effect on MCF-7 cells. These results suggest that OK-432 may augment the therapeutic
effect of TAM in breast cancer. PMID: 9260604, UI: 97407371
Gen Pharmacol 1997 Aug; 29(2):269-73
Polysaccharopeptide from the mushroom Coriolus versicolor possesses analgesic activity but
does not produce adverse effects on female reproductive or embryonic development in mice.
Ng TB, Chan WY, Departments of Biochemistry and Anatomy, Faculty of Medicine, Chinese University
of Hong Kong, Shatin, N.T., Hong Kong.
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. PMID: 9251912, UI: 97395816
Life Sci 1997; 60(25):PL383-7
Polysaccharopeptide from Coriolus versicolor has potential for use against human immunodeficiency
virus type 1 infection.
Collins RA, Ng TB, Department of Biochemistry, The Chinese University of Hong Kong, Shatin,
New Territories.
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. PMID: 9194694, UI: 97338023
Am J Chin Med 1997; 25(1):27-35
Polysaccharide peptide (PSP) restores immunosuppression induced by cyclophosphamide in rats.
Qian ZM, Xu MF, Tang PL, Department of Applied Biology and Chemical Technology, Hong Kong
Polytechnic University, Hung Hom, Kowloon, Hong Kong.
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 a 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. PMID: 9166995, UI: 97309580
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