Scientific Researches On:
Grifola Frondosa (Maitake Mushroom)
USA National Center for Biotechnology Information
21:
Altern Med Rev.
2002 Jun;7(3):236-9.
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Comment in:
Can maitake MD-fraction aid
cancer patients?
Kodama N,
Komuta K,
Nanba H.
Department of Microbial
Chemistry, Kobe Pharmaceutical
University, Kobe, Japan.
Maitake mushroom (Grifola
frondosa) MD-fraction containing
beta-1,6 glucan with beta-1,3
branched chains has previously
exhibited strong anticancer
activity by increasing
immune-competent cell
activity.1,2 In this non-random
case series, a combination of
MD-fraction and whole maitake
powder was investigated to
determine its effectiveness for
22- to 57-year-old cancer
patients in stages II-IV. Cancer
regression or significant
symptom improvement was observed
in 58.3 percent of liver cancer
patients, 68.8 percent of breast
cancer patients, and 62.5
percent of lung cancer patients.
The trial found a less than
10-20 percent improvement for
leukemia, stomach cancer, and
brain cancer patients.
Furthermore, when maitake was
taken in addition to
chemotherapy, immune-competent
cell activities were enhanced
1.2-1.4 times, compared with
chemotherapy alone. Animal
studies have supported the use
of maitake MD-fraction for
cancer.
Publication Types:
PMID: 12126464 [PubMed - indexed
for MEDLINE]
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Effect of maitake (Grifola
frondosa) D-fraction on the
control of the T lymph node
Th-1/Th-2 proportion.
Inoue A,
Kodama N,
Nanba H.
Department of Microbial
Chemistry, Kobe Pharmaceutical
University, Japan.
We have already reported that
the D-Fraction, a beta-glucan
extracted from the fruiting body
of the maitake mushroom (Grifola
frondosa), activates cellular
immunity and expresses
anti-tumor effects. In this
study we investigated the
anti-tumor functions of
D-Fraction in relation to its
control of the balance between T
lymphocyte subsets Th-1 and
Th-2. D-Fraction decreased the
activation of B cells and
potentiated the activation of
helper T cells, resulting in
enhanced cellular immunity. It
also induced the production of
interferon (IFN)-gamma,
interleukin (IL)-12 p70, and
IL-18 by whole spleen cells and
lymph node cells, but suppressed
that of IL-4. These results
suggest that D-Fraction
establishes Th-1 dominance which
induces cellular immunity in the
population that was Th-2
dominant due to carcinoma.
PMID: 11995941 [PubMed - indexed
for MEDLINE]
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[Prevention of postoperative
recurrence of bladder cancer: a
clinical study]
[Article in Chinese]
Yang D,
Li S,
Wang H,
Li X,
Liu S,
Han W,
Hao J,
Zhang H.
Department of Urolagy, Jinan
General Hospital of People's
Liberation Army, Jinan 250031.
OBJECTIVE: To lower
postoperative recurrence rate of
bladder cancer, the prophylactic
effects of five kinds of method
on bladder cancer were
evaluated. METHODS: Between 1982
and 1997, 313 patients after
TURBT or partial cystectomy were
followed up for 2 to 15 years
(average 7.6 years). These
patients were divided into six
groups: BCG, mitomycin C (MMC),
thiotepa, Chinese herb medicine
Zhuling (Grifola umbellata pilat),
afterloading brachytherapy and
control group. The prophylactic
effects of them on postoperative
recurrence of bladder cancer was
evaluated. RESULTS: During the
follow-up, the recurrence rates
were 35.1% in BCG group, 34.9%
in Zhuling group, 41.7% in MMC
group, 52.6% in thiotepa group,
64.7% in control group,
respectively. 25 high-risk
patients with invading or
multiple bladder cancer were
treated by afterloading
brachytherapy. They were
followed up from 12 to 42
months, with a recurrence rate
being 24.0%. CONCLUSIONS: The
prophylactic effect of Zhuling
and BCG on bladder cancer
recurrence was better than MMC.
The vale of thiotepa was not
significant. The afterloading
brachytherapy was of great vale
to invading or recurrent,
multiple bladder cancer.
Publication Types:
PMID: 11829890 [PubMed - indexed
for MEDLINE]
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Effects of maitake (Grifola
frondosa) D-Fraction on the
carcinoma angiogenesis.
Matsui K,
Kodama N,
Nanba H.
Department of Microbial
chemistry, Kobe Pharmaceutical
University, 19-1,
Motoyama-kitamachi 4-chome,
Higashinada-ku, 658-8558, Kobe,
Japan.
We have reported that D-Fraction
extracted from maitake (Grifola
frondosa), activates immune
competent cells, and indicates
anti-tumor activities. The
D-Fraction was observed to
induce angiogenesis in vivo and
to enhance the proliferation
capability and migration
capability of human vascular
endothelial cell in vitro. The
D-Fraction also increased plasma
vascular endothelial growth
factor (VEGF) concentration
significantly. Also VEGF and TNF-alpha
production by the activated
peritoneal macrophages were
enhanced. These results suggest
that the anti-tumor activity of
the D-Fraction is not only
associated with the activation
of the immuno-competent cells
but also possibly related to the
carcinoma angiogenesis
induction.
PMID: 11566496 [PubMed - indexed
for MEDLINE]
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Maitake extracts and their
therapeutic potential.
Mayell M.
mmayell@mediaone.net
Maitake (Grifola frondosa) is
the Japanese name for an edible
fungus with a large fruiting
body characterized by
overlapping caps. It is a
premier culinary as well as
medicinal mushroom. Maitake is
increasingly being recognized as
a potent source of
polysaccharide compounds with
dramatic health-promoting
potential. The most recent
development is the MD-fraction,
a proprietary maitake extract
its Japanese inventors consider
to be a notable advance upon the
preceding D-fraction. The
D-fraction, the MD-fraction, and
other extracts, often in
combination with whole maitake
powder, have shown particular
promise as immunomodulating
agents, and as an adjunct to
cancer and HIV therapy. They may
also provide some benefit in the
treatment of hyperlipidemia,
hypertension, and hepatitis.
Publication Types:
PMID: 11207456 [PubMed - indexed
for MEDLINE]
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Induction of apoptosis in
human prostatic cancer cells
with beta-glucan (Maitake
mushroom polysaccharide).
Fullerton SA,
Samadi AA,
Tortorelis DG,
Choudhury MS,
Mallouh C,
Tazaki H,
Konno S.
Department of Urology, New York
Medical College, Valhalla, New
York 10595, USA.
PURPOSE: To explore more
effective treatment for
hormone-refractory prostate
cancer, we investigated the
potential antitumor effect of
beta-glucan, a polysaccharide of
the Maitake mushroom, on
prostatic cancer cells in vitro.
MATERIALS AND METHODS: Human
prostate cancer PC-3 cells were
treated with various
concentrations of the highly
purified beta-glucan preparation
Grifron-D(R) (GD), and viability
was determined at 24 h. Lipid
peroxidation (LPO) assay and in
situ hybridization (ISH) were
performed to unravel the
antitumor mechanism of GD.
RESULTS: A dose-response study
showed that almost complete
(>95%) cell death was attained
in 24 h with GD > or = 480
microg/mL. Combinations of GD in
a concentration as low as 30 to
60 microg/mL with 200 microM
vitamin C were as effective as
GD alone at 480 microg/mL,
inducing >90% cytotoxic cell
death. Simultaneous use with
various anticancer drugs showed
little potentiation of their
efficacy except for the
carmustine/GD combination
(approximately 90% reduction in
cell viability). The
significantly (twofold) elevated
LPO level and positive ISH
staining of GD-treated cells
indicated oxidative membrane
damage resulting in apoptotic
cell death. CONCLUSION: A
bioactive beta-glucan from the
Maitake mushroom has a cytotoxic
effect, presumably through
oxidative stress, on prostatic
cancer cells in vitro, leading
to apoptosis. Potentiation of GD
action by vitamin C and the
chemosensitizing effect of GD on
carmustine may also have
clinical implications.
Therefore, this unique mushroom
polysaccharide may have great a
potential as an alternative
therapeutic modality for
prostate cancer.
PMID: 10851301 [PubMed - indexed
for MEDLINE]
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The use of mushroom glucans
and proteoglycans in cancer
treatment.
Kidd PM.
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:
PMID: 10696116 [PubMed - indexed
for MEDLINE]
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Mushrooms, tumors, and
immunity.
Borchers AT,
Stern JS,
Hackman RM,
Keen CL,
Gershwin ME.
Division of Rheumatology/Allergy
and Clinical Immunology,
University of California at
Davis School of Medicine, Davis,
California 95616-8660, USA.
Medicinal properties have been
attributed to mushrooms for
thousands of years. Mushroom
extracts are widely sold as
nutritional supplements and
touted as beneficial for health.
Yet, there has not been a
critical review attempting to
integrate their nutraceutical
potential with basic science.
Relatively few studies are
available on the biologic
effects of mushroom consumption,
and those have been performed
exclusively in murine models. In
this paper, we review existing
data on the mechanism of whole
mushrooms and isolated mushroom
compounds, in particular
(1-->3)-beta-D-glucans, and the
means by which they modulate the
immune system and potentially
exert tumor-inhibitory effects.
We believe that the antitumor
mechanisms of several species of
whole mushrooms as well as of
polysaccharides isolated from
Lentinus edodes, Schizophyllum
commune, Grifola frondosa, and
Sclerotinia sclerotiorum are
mediated largely by T cells and
macrophages. Despite the
structural and functional
similarities of these glucans,
they differ in their
effectiveness against specific
tumors and in their ability to
elicit various cellular
responses, particularly cytokine
expression and production.
Unfortunately, our data base on
the involvement of these
important mediators is still
rather limited, as are studies
concerning the molecular
mechanisms of the interactions
of glucans with their target
cells. As long as it remains
unclear what receptors are
involved in, and what downstream
events are triggered by, the
binding of these glucans to
their target cells, it will be
difficult to make further
progress in understanding not
only their antitumor mechanisms
but also their other biological
activities.
Publication Types:
PMID: 10460691 [PubMed - indexed
for MEDLINE]
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Effect of Maitake D-fraction
on cancer prevention.
Nanba H,
Kubo K.
Department of Microbial
Chemistry, Kobe Pharmaceutical
University, Japan.
PMID: 9616756 [PubMed - indexed
for MEDLINE]
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Effects of Lentinus edodes,
Grifola frondosa and Pleurotus
ostreatus administration on
cancer outbreak, and activities
of macrophages and lymphocytes
in mice treated with a
carcinogen, N-butyl-N-butanolnitrosoamine.
Kurashige S,
Akuzawa Y,
Endo F.
Department of Laboratory
Sciences, Gunma University
School of Health Sciences,
Japan.
ICR mice were treated with a
carcinogen, N-butyl-N'-butanolnitrosoamine
BBN), every day for 8
consecutive weeks and the
effects of oral administration
of edible mushrooms on the
induction of urinary bladder
carcinoma and on the activities
of macrophages and lymphocytes
were studied. Bladder carcinoma
were found in all 10 mice (100%)
treated with BBN alone, while we
observed carcinoma only in 9 of
17 mice (52.9%), in 7 of 15 mice
(46.7%) and 13 of 20 mice
(65.0%) treated with Lentinus
edodes, Grifola frondosa and
Pleurotus ostreatus,
respectively. Chemotactic
activity of macrophages was
suppressed in mice treated with
BBN alone but maintained almost
the normal level in mice treated
with BBN plus Lentinus, Grifola
or Pleurotus. Lymphocytes
collected from mice treated with
BBN plus each mushroom showed
almost normal blastogenic
response against concanavalin A,
although those from mice treated
with BBN alone completely
retarded their response.
Cytotoxic activity of
lymphocytes against Yac-1 cells
was also maintained at a normal
level in mice treated with BBN
plus each mushroom. Whereas in
mice treated with BBN alone
significant depression of NK
cell activity occurred.
Significantly higher cytotoxic
activity against P-815 cells was
observed in lymphocytes from
mice treated with BBN plus each
mushroom than that in
lymphocytes from normal mice or
mice treated with BBN alone.
PMID: 9130004 [PubMed - indexed
for MEDLINE]
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Functional properties of
edible mushrooms.
Chang R.
Department of Medicine, Memorial
Sloan-Kettering Cancer Center,
New York, USA.
Edible mushrooms such as
shiitake may have important
salutary effects on health or
even in treating disease. A
mushroom characteristically
contains many different
bioactive compounds with diverse
biological activity, and the
content and bioactivity of these
compounds depend on how the
mushroom is prepared and
consumed. It is estimated that
approximately 50% of the annual
5 million metric tons of
cultivated edible mushrooms
contain functional "nutraceutical"
or medicinal properties. In
order of decreasing cultivated
tonnage, Lentinus (shiitake),
Pleurotus (oyster), Auricularia
(mu-er), Flammulina (enokitake),
Tremella (yin-er), Hericium, and
Grifola (maitake) mushrooms have
various degrees of
immunomodulatory,
lipid-lowering, antitumor, and
other beneficial or therapeutic
health effects without any
significant toxicity. Although
the data for this functional
food class are not as strong as
those for other functional foods
such as cruciferous vegetables,
because of their potential
usefulness in preventing or
treating serious health
conditions such as cancer,
acquired immune deficiency
syndrome (AIDS), and
hypercholesterolemia, functional
mushrooms deserve further
serious investigation.
Additionally, there is a need
for epidemiological evidence of
the role of this functional food
class.
Publication Types:
PMID: 9110582 [PubMed - indexed
for MEDLINE]
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Activity of maitake
D-fraction to inhibit
carcinogenesis and metastasis.
Nanba H.
Department of Microbial
Chemistry, Kobe Pharmaceutical
University, Japan.
Publication Types:
PMID: 8526356 [PubMed - indexed
for MEDLINE]
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[Prophylactic effects of
zhuling and BCG on postoperative
recurrence of bladder cancer]
[Article in Chinese]
Yang DA,
Li SQ,
Li XT.
General Hospital of Jinan Unit
of People's Liberation Army.
The prophylactic effects of
Chinese herbal medicine Zhuling
(Grifola umbellata pilat) and
BCG on bladder cancer after
TURBT and partial cystectomy
were evaluated. 146 patients
with bladder cancer were divided
into 3 groups, Zhuling, BCG, and
control group. Follow-up for
48-124 months (average 70.8
months) showed that the tumor
recurrence rate was 33.3%, 34.3%
and 65.1%, respectively.
Compared to the control group,
the recurrence rate of Zhuling
group and BCG group was
significantly decreased (P <
0.01). The effect of Zhuling was
similar to that intravesical BCG.
Zhuling was cheaper and
convenient in usage, and no side
effects.
Publication Types:
PMID: 7842985 [PubMed - indexed
for MEDLINE]
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[Inhibitory effect of Chinese
herb medicine zhuling on urinary
bladder cancer. An experimental
and clinical study]
[Article in Chinese]
Yang DA.
General Hospital of Jian Unit of
People's Liberation Army.
Inhibitory effect of Zhuling (Grifola
umbellata pilat) on urinary
bladder cancer was determined
experimentally and clinically.
The results showed that zhuling
inhibited significantly the
induction of bladder cancer in
rats exposed to
N-butyl-N-(4-hydroxybutyl)
nitrosamine (BBN), decreasing
from 100% (18/18) in control
group to 61.1% (11/18) in
zhuling (P less than 0.01).
Zhuling was given to 22 patients
with recurrent bladder cancer
after TUR or partial cystectomy.
The patients were followed up
for 12 to 38 months (average
26.5 months). Bladder cancer
recurred in seven of the
patients with a longer
recurrence interval (19.2
months) after medication than
before medication (P less than
0.05). The remaining 15 patients
had no recurrence. The mechanism
of Zhuling is discussed.
Publication Types:
PMID: 1935440 [PubMed - indexed
for MEDLINE]
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Physiochemical properties and
antitumor activities of
chemically modified derivatives
of antitumor glucan "grifolan
LE" from Grifola frondosa.
Adachi Y,
Ohno N,
Ohsawa M,
Sato K,
Oikawa S,
Yadomae T.
Antitumor glucan, grifolan LE (GRN
LE), from Grifola frondosa was
chemically modified to examine
the structure-function
relationship of the products.
Modification by periodate,
borohydride and acid hydrolysis
of side chains of GRN LE did not
alter properties such as helical
conformation and antitumor
activity of GRN LE. Introduction
of carboxylic acid groups into
the side chains by oxidation
with periodate and with sodium
chlorite (GRN LE-PC), and
substitution with carboxymethyl
(CM) or hydroxyethyl (HE) groups
abolished the gel-forming
ability of GRN LE. Significant
antitumor activity was observed
in all of the derivtives having
gel-forming ability as well as
some derivatives having no such
ability. These results suggested
that essential factors required
for antitumor activity were
(1----3)-beta-D-glucosyl
linkages and high molecular
weight, and that accessory
groups could be linked to the
main chain without loss of
antitumor activity in a higher
ratio than that of gel-forming
ability.
PMID: 2805163 [PubMed - indexed
for MEDLINE]
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Antitumor activity exhibited
by orally administered extract
from fruit body of Grifola
frondosa (maitake).
Hishida I,
Nanba H,
Kuroda H.
PMID: 3203420 [PubMed - indexed
for MEDLINE]
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Host-mediated antitumor
effect of grifolan NMF-5N, a
polysaccharide obtained from
Grifola frondosa.
Takeyama T,
Suzuki I,
Ohno N,
Oikawa S,
Sato K,
Ohsawa M,
Yadomae T.
Tokyo College of Pharmacy,
Japan.
The antitumor mechanism of
grifolan NMF-5N, a
beta-1,3-glucan obtained from
mycelia of Grifola frondosa, was
examined. Grifolan NMF-5N did
not show direct cytocidal effect
on cultured tumor cells.
However, intraperitoneal
injection of grifolan NMF-5N
increased the number of
peritoneal exudate cells and
peritoneal adherent cells which
showed cytostatic activity
towards syngeneic tumor cells.
In an in vivo assay, the
administration of carrageenan,
an inhibitor of macrophage
function, reduced the antitumor
activity of grifolan NMF-5N. The
delayed-type hypersensitivity
reaction was augmented in the
grifolan NMF-5N-administered
mice. The administration of
NMF-5N augmented the induction
of cytotoxic T cells but the
antitumor activity of grifolan
NMF-5N was reduced in athymic nu/nu
mice. In addition, the treatment
with anti-Thy 1,2 antibody and
complement C' of spleen cells
taken from mice which showed
regression of tumor due to
grifolan NMF-5N, reduced the
neutralizing effect in Winn
assay. These results suggested
that grifolan NMF-5N shows
antitumor activity via
host-mediated mechanisms and
both macrophages and T cells
play important roles in the
mechanisms.
PMID: 3446772 [PubMed - indexed
for MEDLINE]
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The chemical structure of an
antitumor polysaccharide in
fruit bodies of Grifola frondosa
(maitake).
Nanba H,
Hamaguchi A,
Kuroda H.
PMID: 3607939 [PubMed - indexed
for MEDLINE]
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Antitumor effect of
polysaccharide grifolan NMF-5N
on syngeneic tumor in mice.
Suzuki I,
Takeyama T,
Ohno N,
Oikawa S,
Sato K,
Suzuki Y,
Yadomae T.
Antitumor activity of grifolan
NMF-5N, a beta-1,3-glucan
obtained from mycelia of Grifola
frondosa, was examined. Grifolan
NMF-5N showed antitumor
activities in allogeneic and
syngeneic murine tumor systems.
In the allogeneic tumor system,
a potent antitumor activity over
95% was observed against the
solid form of sarcoma 180 when
grifolan NMF-5N was injected
intraperitoneally (i.p.) at
25-200 micrograms/mouse daily
for 10 successive days. In the
syngeneic tumor systems,
significant antitumor activities
were observed against Meth A
fibrosarcoma and MM 46 carcinoma
by injection at 100
micrograms/mouse daily for 5
successive days, especially i.p.
injection at day 7-11, when the
tumor cells were inoculated
subcutaneously (s.c.) on day 0.
Moreover, when grifolan NMF-5N
was injected i.p. every other
week, significant antitumor
activity was also observed. In
addition, a single treatment
with grifolan NMF-5N at 500
micrograms/mouse showed
antitumor activities. Grifolan
NMF-5N exhibited antitumor
activities against these two
syngeneic tumors by intraveneous
(i.v.) injection. However, a
marked inhibitory activity was
observed by intratumorous (i.t.)
injection against Meth A
fibrosarcoma but not against
MM46 carcinoma. These results
suggest that antitumor
activities of grifolan NMF-5N in
murine syngeneic tumor systems
depend on not only dosage but
also injection routes and
timing.
PMID: 3598845 [PubMed - indexed
for MEDLINE]
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Potentiation of host-mediated
antitumor activity in mice by
beta-glucan obtained from
Grifola frondosa (maitake).
Adachi K,
Nanba H,
Kuroda H.
PMID: 3594655 [PubMed - indexed
for MEDLINE]
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