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Trametes
versicolor (L. ex Fr.)
Pil.
(Trametes=one who is
thin; versicolor=variously colored)
Synonyms
Boletus versicolor,
Polyporus versicolor (Gilbertson and Ryvarden, 1987). Coriolus
versicolor (L. Fr.) is often used for T. versicolor, but
Trametes is now generally accepted as correct (Arora, 1994).
Other synonyms less frequently used include Polystictus versicolor Fr. and
Polyporus versicolor (Arora, 1986).
Other Common names
In Japan, T.
versicolor is also known as "Kawaratake," which
means mushroom by the river bank (Namba, 1980). In China, the
fungus is called "yun-zhi." meaning cloud fungus
(Yang et al, 1993).
Description and Habitat
This common denizen of
the woods is true to its name, as the multi-colored cap resembles
turkey tails. Its fan-shaped fruiting bodies grow in
overlapping clusters on dead logs. The top is zoned, usually in
shades of brown, white, gray, or blue (tough this is variable),
and it sports hairy bands. The underside of the cap is white and
shows minute pores which do not discolor after scratching.
Range
T. versicolor is
common worldwide. I have seen it growing in many parts of
the United States and Europe, and it grows throughout China (Yang
et al, 1993).
History
For the year 1987 in
Japan, PSK ("polysaccharide Kureha," which is extracted
from turkey tail) accounted for 25.2% of the total national
expenditure for anticancer agents (Fukushima, 1989). Florists in
Europe recently adopted this fungus as one of the top species for
commercial design (Poppe, 1991).
Chemistry
The lipid fraction from
the carpophores of T. versicolor amounts to 1.7% of the
total weight and contains the lanostane-type tetracyclic
triterpenoid ergosta7,22,dien-3(-ol as the major sterol (common
in many other Polyporaceae), along with smaller amounts of ergost-7-en-3-ol (fungisterol) and ergosterol (Yokoyama et al,
1975; Endo. 1981). They also contain (sitosterol (Kim et al,
1978) and hydroxymethylquinoline (Abraham and Spaso, 1991). The
two principal immunologically active fractions are PSK or
"Krestin," a water-soluble, protein-bound
polysaccharide that has (-1, 4-glucan as its main component as
well as (-1,3 linkages and 38% protein (Sakagami and Takeda,
1993), and PSP, a polysaccharide peptide consisting of 10%
peptides and 90% polysaccharides (Yang et al, 1993). Miyazaki et
al (1974) isolated an antitumor polysaccharide that did not
contain nitrogen and called it coriolan.
Pharmacology
Pharmacological
activities that may be due to the protein-bound polysaccharide.
PSK include the
inhibition of sarcoma 180 (Hirase et al, I976a; Ueno et al, 1978;
Yan, 1985); improvement in the functioning of blood vessels (Ito
and Hidaka, 1980a); support of hepatic function (Ito and Hidaka,
1980b); restoration of serum lysozyme content and normalization
of spleen index in irradiated mice (Cai et al, 1987); immune
function enhancement (Iwaguchi, 1985), and the possible
prevention of liver cancer (Wang, 1989). Against lethal
cytomegalovirus infection, the action of PSK appears to be
through NK cell activation (Ebihara and Minamishima, 1984). Also,
nitrogen-containing polysaccharides extracted from T. versicolor mycelia increase antibacterial potency and
prolong antibacterial effects of antibiotics and can increase
antibiotic sensitivity in antibiotic-resistant bacteria (Kureha
Chemical Industry Co., 1978).
Two polyoxygenated
ergosterol derivatives showed cytotoxicity (in vitro) against
hepatoma cells (Valisolalao et al, 1983). T. versicolor has
been used in the control of the tobacco mosaic virus found on Nicotiana
tabacum (Asano et al, 1979).
Animal studies have
shown that PSK, which is derived from the mycelium, has
immune-enhancing activity and a broad antineoplastic scope. It
has been shown to prolong the survival time of irradiated mice,
stimulate phagocytotic activity of macrophages, and improve the
functions of the reticuloendothelial system (Zhu, 1987). In cyclophosphamide-induced granulocytopenia in mice, PSK (i.p.)
caused a significant increase in granulocyte production (Mayer
and Drew, 1980) PSK (oral) restored antibody (IgG) production in
mice bearing sarcoma 180, hut not in normal mice (Nomoto et al
1975).
In regard to PSK's
antitumor properties, it acts directly on tumor cells, as well as
indirectly in the host to boost cellular immunity. It has shown
antitumor activity in animals with adenosarcoma, fibrosarcoma,
mastocytoma, plasmacytoma, melanoma, sarcoma, carcinoma, and
mammary, colon, and lung cancer (Tsukagoshi et al, 1984). An
intriguing feature of this compound is that injection of PSK at
one tumor site has been shown to inhibit tumor growth in other
sites, thus helping to prevent metastasis (Ebina et al, 1987b).
Also, PSK's antitumor activity is enhanced in combination with
radiation, chemotherapy, or immunotherapy. Oral administration of
PSK as 10% and less of rat feeds suppressed carcinogen-induced
cancers of the colon, esophagus, breast, and lung (Tsukagoshi et
al, l984).
PSK has also
demonstrated antiviral activity. It may inhibit HIV infection by
modifying the viral receptor or by stopping HIV from binding with
lymphocytes (Tochikura et al 1987a). Another mechanism through
which PSK is reported to have general antiviral activity is
through the stimulation of interferon production (Ebina et al,
l987a).
PSP is an
immunostimulant extracted from T. versicolor mycelia.
Although similar to PSK, which is also extracted from the
mycelia, PSP is devoid of the sugar fucose while PSK is without
the sugars rhamnose and arabinose. The major sugar in PSP is
glucose, and the polysaccharides main chain is linked by beta 1-3 and beta
1-4 glycosides. PSP has shown activity by the oral route and by
injection (i.p.). In normal mice, oral dose of PSP (0.5-2 g/kg)
caused greatly increased phagocytic activity, comparable to
Acanthopanax (300 mg/kg, oral). PSP increased T-cell numbers (in vitro),
interferon production (in vitro), and increased
interleukin production in mice (PSP, 1,500 mg/kg/day X5, orally).
Co-treatment of mice with PSP and cyclophosphamide resulted in a
significant prevention of decreases in white blood cell and IL-2
production. In tumor-bearing mice, PSP stopped thymus atrophy
and increased serum IgG values, PSP showed tumor-inhibiting
activity in animals with sarcoma 180, P388 leukemia,
monocytic leukemia, Ehrlich ascitic tumor, histiocytic lymphoma,
human lung adenocarcinoma, and various cancers of the liver,
stomach, nose, and throat (Yang, 1993).
A glycoprotein obtained
from the mycelia of Trametes spp. showed activity (in
animal and in vitro tests) against experimental
hypertension. diabetes, cancer, thrombosis, and rheumatism. The
protein inhibits blood platelet aggregation and is analgesic,
antipyretic, antihyperlipemic, anti-arrhythmic,
anti-inflammatory, and vasodilating. It has also been shown to
reverse conditions associated with nephron disorders, improve
proteinuria and proteinemia-associated conditions, and regulate
prostaglandin formation and degradation (lkuzawa, 1985).
An extracellular
polysaccharide from T. versicolor administered to mice
(i.p. or oral) challenged with herpes or influenza viruses caused
serum interferon induction and inhibited a decrease in
phagocytosis (Chen, 1986).
Whole T. versirolor has
been shown to lower serum cholesterol in animals (Yagishita et
al, 1977) and, in combination with the herb Artragalus
membranaceus Bunge, it has been found to enhance neutrophil
function and speed recovery in rabbits suffering from burns (Liu
et al, 1985). Finally, a powdered extract (from a 70% ethanolic
tincture) of this species was tested in rats by injection in a
Hippocratic screening of higher fungi and demonstrated mild
tranquilizing and diuretic activity (Malone et at, 1967).
Human Clinical
Studies
PSK has been used both
orally and intravenously as an immune adjuvant in clinical
medicine, Cancer patients given 3 g of PSK per day have shown
increased interferon production (Ebina et al, 1987a).
In cancer patients, PSK also antagonistically elevates the
activity of phosphofructokinase and shows antioxidant activity,
working as a superoxide and hydroxyl radical scavenger (Nakamura
et al, 1986). PSK has been shown to be effective against many
human cancers (Hotta et al, 1981) but seldom with satisfactory
results administered alone. In combination with radiation in
stage III uterine cervical cancer patients, PSK (3-6 g/day)
prolonged the life span and appeared to have enhanced the
sensitivity of the cancers to radiation therapy. One study
performed at the Department of Gynecology. National Cancer Center
Hospital in Tokyo (Kasamatsu, 1982) tested the influence of PSK
on the survival rate with cervical cancer patients. PSK was given
orally in the dose of 3-6 grams a day in conjunction with
radiation therapy. After radiation, patients having no observed
tumor cells remaining was 36% with PSK and 11% without, Two-year
survival rate was 94% with PSK and 74% without; 3-year survival
rate was 85% and 59%, 5-year survival rate 64% and 41%
respectively. The rate of cancer deaths within S years was 21%
with PSK and 52% without.
Improved survival rates
have also been reported in gastric cancer patients from PSK (6
g/day) in a combination treatment with the chemotherapeutic agent
tegafur following gastrectomy and patients with postoperative
stomach cancer. In a randomized, controlled study with 462
curatively resected colorectal cancers, PSK was given orally for
over 3 years following mitomycin C (by i.v. on the day of surgery
and 1 day following) and 5-fluorouracil (5-FU) orally for .5
months. At the time of reporting, the average study follow-up was
4 years. The increased disease-free survival curve of the
PSK group over the control group (who only received the 2 drugs)
was statistically significant (Mitorni et al, 1992). In another
similar study, PSK was administered after the same
chemotherapeutic regime as the previous study to 56 patients and
a placebo to a group of 55 control patients. The rate of
remissions and the survival rate in the patients taking PSK was
significantly higher than the control group. Enhanced immune
functions, including enhanced polymorphonuclear leukocyte
activity was said to be a significant factor in explaining the
results (Torisu et at, 1990). PSK was tested as an adjuvant
immunotherapy in a group of patients with carcinoma of the
nasopharynx (n=2 1), and found to significantly increase (35 yersus
25 months) the median survival time over the control group (n=17)
as well as the 5-year survival rate (28% versus 15%). All
patients in both groups had previous radiotherapy with or without
chemotherapy (Go & Chung, 1989). Another earlier study with
nasopharyngeal carcinoma patients (n=67) reported similar results
(Chung et al, 1987). The dose was 1 gram 3 times daily for a
minimum of 1 month. Three cases of toxicity were noted.
Other uncontrolled
clinical studies have reported enhanced or recovered cellular
immunity from PSK in patients with glomerulonephritis,
sarcoidosis, and idiopathic nephrotic syndrome. Symptoms
decreased, and relapse was prevented. Improved symptoms and
normalization of immunity were reported in systemic lupus
erythematosus, and in cases of lupus, chronic rheumatoid
arthritis, sclerosis, Beçhet’s disease, and dermatomyositis,
peripheral lymphocytes showed recovery of blastogenesis. Others
have reported that PSK causes a significant decrease in LDL
cholesterol in hyperlipidemia (stage IIa) patients, a significant
decrease in cyclophosphamide-induced chromosomal damage in
children (Tsukagoshi et al, 1984), fewer sick days! and increased
immunity in patients with recurrent genital herpes (3-5 g/day)
(Kawana, 1985).
A controlled clinical
trial of PSP was conducted in 485 cancer patients (211 control
patients) treated with the polysaccharide-peptide (3 g/day for 30
days orally) in combination with radio- and chemotherapies. The
patients were diagnosed with cancers of the esophagus, stomach,
and lung. As a result of PSP, side effects from the conventional
therapies most significantly lessened in the categories of pain,
poor appetite, tiredness, weakness, and dryness of the mouth and
throat. The clinicians noted that in TCM, this indicates an
invigorating action on the heart and spleen. Compared to control
patients, body weight in the PSP group was significantly higher,
and their T-cell ratio, NK cell activity, and IL-2 levels were
also higher. To counteract the decreases in white blood cell,
hemoglobin, and platelet levels which accompany chemo- and
radiotherapy, batyl alcohol is often given at the same time. PSP
in place of batyl alcohol produced comparable results, The rate
of remission in the esophageal cancer patients who received PSP
plus chemotherapy was 72%, whereas those on chemotherapy alone
had a remission rate of 42%. PSP also raised the one-year
survival rate for this type of cancer by 11 %. The main
immunologic pathways activated by PSP to inhibit tumors are
through helper T-cell, NK cell, and complement C3 (Yang. 1993).
In breast cancer patients treated with 4’epidoxorubicin and
cyclophosphamide, PSP stabilized and nearly prevented white blood
cell decreases from the chemotherapy (Shui et al, 1992).
Toxicity
Unlike many standard
anticancer drugs, the PSK in T. versicolor produces few,
if any, side effects on the bone marrow or other organs, and it
shows no immunosuppressive action. In general, T. versicolor has
very low levels of toxicity (Su et al, 1987) and produces few or
no side effects (Tsukagoshi et al, 1984). The oral LD5O of PSP is
reported as 10.0 gm /kg. Negative results were found on the Ames
and chromosome distortion tests (Yang & Jong, 1989).
Uses in Traditional
Medicine
The taste and energy is
sweet and slightly warm; enters the spleen and heart meridians;
invigorates the spirit (Yang et al, 1993).
In TCM, T. versicolor
is used to clear dampness, reduce phlegm, heal pulmonary
disorders (Ying et al, 1986), strengthen the physique, increase
energy. and benefit people with chronic diseases (Yang &
Jong, 1989). In Mexican folk medicine, the fungus is used to cure
ring-worm or impetigo of the skin (Alfaro et al, 1983)
Medical Uses
In China, it is
considered useful for infection and/or inflammation of the upper
respiratory, urinary, and digestive tracts, curative to liver
ailments, including hepatitis B and chronic active hepatitis, and
is used for general immune weakness and tumors (Ying et al,
1987).
Preparation and
Dosage
Take as desired in tea,
up to 20 g 3X /day. Powder the dried fruiting bodies and take up
to 5 grams a day in capsules. For PSP, one gram 3 times
daily (Yang)
Related Species
T. pubescens has
exhibited anti-tumor activity (Shibata et al, 1968), and T. hirnetus
is also active against sarcoma 180 in mice, and it is a
popular folk remedy for benefiting lung diseases, stopping
coughing, and promoting the regeneration of muscle (Ying et al,
1937). Coriolus consors contains coriolin, an antibiotic
that has been shown to inhibit Gram-positive bacteria and Trichomonas
vaginalis (Takeuchi et al, 1969). In addition, many species
of Trametes have shown antibacterial activity (Hervey, 1947).
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