Immune Fx
References and Research Articles
LENTINULA EDODES (SHIITAKE)
Oncol Rep 2000 May-Jun;7(3):599-601
Effects of lentinan on colorectal carcinogenesis in mice with ulcerative colitis.
Mitamura T, Sakamoto S, Suzuki S, Yoshimura S, Maemura M, Kudo H, Medical Research Institute,
Tokyo Medical and Dental University, Tokyo, Japan.
Lentinan; i.e., polysaccharides extracted from a kind
of black mushroom shiitake, has been clinically applied
as an antitumor and antimetastatic drug, and has been
reported to prevent both chemical and viral carcinogenesis.
It is known that lentinan affects the tumorous vascular
system resulting in the induction of hemorrhagic necrosis
which is dependent on T-cells in the tumor. Repeated mucosal
necrosis-regeneration sequence in chronic ulcerative colitis
induced with 3% dextran sulfate sodium led to colorectal
carcinogenesis in azoxymethane-pretreated mice. In the
present study, the additive treatment with lentinan in
the azoxymethane-dextran sulfate sodium treated mice enhanced
the colorectal high-grade dysplasia, though not significantly,
and the splenic weight. This may show the proliferation
of pathogenic splenic T cells resulting in a change for
the worse of ulcerative colitis, anemia induced with hemorrhage
and colorectal carcinogenesis; i.e., high-grade dysplasia
of the mucosa and/or invasive adenocarcinomas of the colorectum.
The present results may recommend chemoimmunotherapy while
using lentinan, but not immunotherapy using lentinan alone,
is indicated for the management of cancer patients. PMID:
10767375
Inhibition of human colon carcinoma development by
lentinan from shiitake mushrooms (Lentinus edodes).
Ng ML, Yap AT., J Altern Complement Med 2002 Oct;8(5):581-9
OBJECTIVES: Lentinan was extracted from shiitake mushrooms
(Lentinus edodes) via a new cost-effective procedure
that resulted in high purity (88%) and yield. Unlike
previous reports whereby the lentinan was given parenterally,
in this study the emphasis was on the oral administration
of lentinan. The goal is to document whether the efficacy
of the antitumor property is still expressed through
this route of administration. DESIGN: Initial study
on the action of lentinan was conducted using murine
lymphoma (K36) cells in a AKR mouse model. Further investigation
on the effectiveness of the extracted lentinan was then
performed using human colon-carcinoma cell lines in
mice. Six established human colon-carcinoma cell lines
segregated into three groups of different degrees of
differentiation were used in this study. One group was
not fed (control) and the second group was prefed with
lentinan for 7 days prior to inoculations with the cancer
cells. The size of the tumors that developed was rated
after 1 month. RESULTS: Significant regression in tumor
formation was observed in prefed mice compared to control
(unfed) mice when K36 or human colon-carcinoma cells
were used. Significant reductions in the size of the
tumors were observed in mice prefed with lentinan. Follow-up
investigation proceeded with the use of nude mice (athymic).
Lymphocytes extracted from AKR mice prefed with lentinan
for 7 days were inoculated into the nude mice. This
was then followed by inoculation of the human colon-carcinoma
cell lines into these mice. Much smaller tumors were
formed in nude mice inoculated with lymphocytes, in
contrast to the larger tumor formed in nude mice without
lymphocytes inoculation. CONCLUSION: This study showed
that the antitumor property of lentinan was maintained
with oral administration. In addition, "primed"
lymphocytes, when given passively to immunodeficient
mice, were able to retard the development of tumors
in these mice.
PMID: 12470439 [PubMed - indexed for MEDLINE]
Arch Pharm Res 2000 Feb; 23(1):79-86
Generation of nuclear hybrids overcoming the natural barrier of incompatibility: transfer
of nuclei from Lentinula edodes into protoplasts of Coriolus versicolor.
Kim C, Choi EC, Kim BK, Research Institute of Pharmaceutical Sciences, College of Pharmacy,
Seoul National University,
Heterokaryotic nuclear hybrids overcoming the natural barriers of incompatibility have
been studied in basidiomycetes. To produce these nuclear hybrids between incompatible mushrooms,
which have several potent pharmacological effects, nuclear transfer was performed between
Lentinula edodes and Coriolus versicolor. Nuclei from serine auxotrophs of Lentinula edodes,
LE207 (Ser-) were transferred into the protoplasts of arginine auxotrophs of Coriolus versicolor,
CV17 (Arg-), using 30% polyethylene glycol 4000 in 10 mM CaCl2-glycine solution (pH 8.0).
Nuclear transfer progenies were selected by nutritional complementation on minimal media
supplemented with 0.6 M sucrose. The progenies were classified based on colony morphology
to L. edodes-like, C. versicolor-like and non-parental type. Most of the progenies grew
slower than either parent. The number of nuclei per cell was similar but the DNA content
varied between progenies. The isozyme patterns of nuclear hybrids resembled either of the
parent profiles or showed a mixed profile. PMID: 10728662, UI: 20191006
Caries Res 2000 Jan-Feb; 34(1):94-8
Anticaries effect of a component from shiitake (an edible mushroom).
Shouji N, Takada K, Fukushima K, Hirasawa M, Department of Microbiology, Nihon University
School of Dentistry at Matsudo, Chiba, Japan.
The caries-inhibiting effect of the extract from shiitake (Lentinus edodes), the most
popular edible mushroom in Japan, was studied both in vitro and in vivo. Shiitake extract
showed an inhibitory effect on water-insoluble glucan formation from sucrose by crude glucosyltransferases
of Streptococcus mutans JC-2 and Streptococcus sobrinus OMZ-176. The firmly adherent plaque
in the artificial plaque formation test was strongly inhibited by shiitake extract. The
reduction of firmly adherent plaque caused an increase in the incidence of non- and loosely
adherent plaque and a decrease in total plaque formation. A significantly lower caries score
was observed in specific pathogen-free rats infected with S. mutans JC-2 and fed with a
cariogenic diet containing 0.25% shiitake extract as compared with controls fed the cariogenic
diet without shiitake extract. PMID: 10601791, UI: 20069269
J Med 1998; 29(5-6):305-30
A placebo-controlled trial of the immune modulator, lentinan, in HIV-positive patients:
a phase I/II trial.
Gordon M, Bihari B, Goosby E, Gorter R, Greco M, Guralnik M, Mimura T, Rudinicki V, Wong
R, Kaneko Y
AID Lentinan is a beta 1-->3 glucan isolated from Lentinus edodes (Shiitake mushroom)
which has immune modulating properties. We have conducted two phase I/II placebo-controlled
trials on a total of 98 patients. In one study at the San Francisco General Hospital (SFGH),
ten patients each were administered 2, 5, or 10 mg of lentinan or placebo i.v. once a week
for eight weeks. In the second study at the Community Research Initiative in New York (CRI),
two groups of 20 patients each were administered 1 or 5 mg of lentinan i.v. twice a week
for 12 weeks, and ten patients were administered placebo (vehicle containing mannitol plus
dextran 40) i.v. twice a week. Entry criteria were an HIV positive test, CD4 levels of 200-500
cells, age 18-60 years, and without current opportunistic infections. This study confirms,
in Caucasian subjects also, the good tolerability of lentinan observed in Japanese cancer
patients. Side effects were mainly mild, especially when infusion was carried out over a
30-minute period. In the SFGH study, where administration was over a ten minute period,
there were nine side effects severe enough to be reported to the FDA (one case each of anaphylactoid
reaction, back pain, leg pain, depression, rigor, fever, chills, granulocytopenia and elevated
liver enzymes) and there were four patients who discontinued therapy because of side effects.
In the CRI study, where infusion was over a 30-minute period, there were no side effects
reportable to the FDA and there were four dropouts due to side effects or personal preference.
Most side effects resolved promptly after the discontinuation of medication, and all of
them were relieved within 24 hours. Patients in the study have shown a trend toward increases
in CD4 cells and in some patient’s neutrophil activity. Because of the small numbers,
these values do not have statistical significance. Inasmuch as no side effects such as anemia,
leukopenia, pancreatitis or neuropathy were seen, and in view of the positive effects of
lentinan on certain surrogate markers (recognizing that these were small studies), we recommended
a long-term clinical trial of lentinan in combination with didanosine (ddI) or zidovudine
in HIV positive patients. Most patients in these trials did not have measurable p24 levels.
In the CRI trials of ten patients with elevated p24 levels, eight on lentinan and two on
placebo had decreased p24 levels. Of these decreases, those with lentinan and one with placebo
were marked. These results were provocative and needed confirmation. Subsequent to this
study, a trial of lentinan in combination with didanosine (ddI) showed a mean increase of
142 CD4 cells/mm3 over a twelve month period, in contrast to a decrease in CD4 cells in
patients on ddI alone (Gordon et al. 1995). Publication Types: Clinical trial, phase I,
Clinical trial, phase ii, Randomized controlled trial S Activities Division, San Francisco
General Hospital, CA, USA. PMID: 10503166, UI: 99432784
Int J Antimicrob Agents 1999 Feb; 11(2):151-7
Three kinds of antibacterial substances from Lentinus edodes (Berk.) Sing. (Shiitake, an
edible mushroom).
Hirasawa M, Shouji N, Neta T, Fukushima K, Takada K, Department of Microbiology, Nihon University
School of Dentistry at Matsudo, Chiba, Japan.
Three kinds of antibacterial substances were extracted
by chloroform, ethylacetate or water from dried Shiitake
mushrooms (Lentinus edodes). These substances possess
efficient antibacterial activities against Streptococcus
spp., Actinomyces spp., Lactobacillus spp., Prevotella
spp., and Porphyromonas spp. of oral origin. In contrast,
other general bacteria, such as Enterococcus spp., Staphylococcus
spp., Escherichia spp., Bacillus spp., and Candida spp.
were relatively resistant to these substances. Chloroform
extracts had bactericidal activity against both growing
and resting bacterial cells of S. mutans and P. intermedia,
whereas the other two extracts showed bacteriostatic
activity against both growing and resting bacterial
cells of S. mutans and resting bacterial cell of P.
intermedia. The antibacterial activity of chloroform
extracts and ethylacetate extracts were relatively heat-stable.
The water extract was heat-labile. PMID: 10221419, UI:
99236608
Phytother Res 1999 Mar; 13(2):133-7.
Effects of shiitake (Lentinus edodes) extract on human neutrophils and the U937 monocytic
cell line.
Sia GM, Candlish JK, Department of Biochemistry, Faculty of Medicine, National University
of Singapore.
The aqueous extract of the shiitake mushroom was found to decrease IL-1 production and
apoptosis in human neutrophils, as measured by ELISA and flow cytometry respectively. It
was found to increase IL-1 production and apoptosis in the U937 monocytic cell line. The
extract showed no significant effects on the superoxide production of both neutrophils and
U937 cells, as measured by chemiluminescence. The extract was further separated into high
and low molecular weight components, and it was found that the low molecular weight component
retained the activity of the whole extract. This further suggests that the active substance
is a novel compound distinct from lentinan, a well-studied high molecular weight anti-tumour
agent found in shiitake
Biochem Mol Biol Int 1996 Jul; 39(4):679-85
Preparation and specificity of antibodies to an anti-tumor
beta-glucan, lentinan.
Mizono M, Minato K, Tsuchida H, Graduate School of Science
and Technology, Kobe University, Japan.
Antibodies against beta-glucan, lentinan from "Shiitake"
(Lentinus edodes), were raised in the rabbit by subcutaneous
immunization. Our antibodies did not recognize the other
polysaccharides such as amylose, dextran, laminarin
and galactan. It was proved that lentinan contents in
mushroom could be measured by ELISA with the anti-lentinan
antisera. Its contents were 3.5 mg/g fresh weight in
Lentinus edodes. However, lentinan was not contained
in Agaricus brazei, Agaricus bisporus and Ramaria bitrytis.
PMID: 8843335, UI: 97000193
Carcinogenesis 1999 Aug; 20(8):1637-40
In vitro chemopreventive effects of plant polysaccharides (Aloe barbadensis miller, Lentinus
edodes, Ganoderma lucidum and Coriolus versicolor).
Kim HS, Kacew S, Lee BM, Division of Toxicology, College of Pharmacy, Sungkyunkwan University,
Changan-ku, Chunchun-dong, Kyunggi-do, Suwon 440-746, Korea.
A plant polysaccharide, Aloe gel extract, was reported
to have an inhibitory effect on Benzo [a]pyrene (B[a]P)-DNA
adduct formation in vitro and in vivo. Hence, chemopreventive
effects of plant polysaccharides [Aloe barbadensis Miller
(APS), Lentinus edodes (LPS), Ganoderma lucidum (GPS)
and Coriolus versicolor (CPS)] were compared using in
vitro short-term screening methods associated with both
initiation and promotion processes in carcinogenesis.
In B[a]P-DNA adduct formation, APS (180 micrograms/ml)
was the most effective in inhibition of B[a]P binding
to DNA in mouse liver cells. Oxidative DNA damage (by
8-hydroxydeoxyguanosine) was significantly decreased
by APS (180 micrograms/ml) and CPS (180 micrograms/ml).
In induction of glutathione S-transferase activity,
GPS was found to be the most effective among plant polysaccharides.
In screening anti-tumor promoting effects, APS (180
micrograms/ml) significantly inhibited phorbol myristic
acetate (PMA)-induced ornithine decarboxylase activity
in Balb/3T3 cells. In addition, APS significantly inhibited
PMA-induced tyrosine kinase activity in human leukemic
cells. APS and CPS significantly inhibited superoxide
anion formation. These results suggest that some plant
polysaccharides produced both anti-genotoxic and anti-tumor
promoting activities in in vitro models and, therefore,
might be considered as potential agents for cancer chemoprevention.
PMID: 10426820, UI: 99355758
Curr Med Chem 2000 Jul; 7(7):715-29
Immunomodulation and anti-cancer activity of polysaccharide-protein
complexes.
Ooi VE, Liu F, Department of Biology, The Chinese University
of Hong Kong, Shatin, N.T., Hong Kong.
In the last three decades, numerous polysaccharides
and polysaccharide-protein complexes have been isolated
from mushrooms and used as a source of therapeutic agents.
The most promising biopharmacological activities of
these biopolymers are their immunomodulation and anti-cancer
effects. They are mainly present as glucans with different
types of glycosidic linkages such as (1-->3), (1-->6)-beta-glucans
and (1-->3)-alpha-glucans, and as true herteroglycans,
while others mostly bind to protein residues as polysaccharide-protein
complexes. Three antitumor mushroom polysaccharides,
i.e. lentinan, schizophyllan and protein-bound polysaccharide
(PSK, Krestin), isolated respectively, from Lentinus
edodes, Schizophyllum commune and Coriolus versicolor,
have become large market items in Japan. Lentinan and
schizophyllan are pure beta-glucans, whereas PSK is
a protein-bound beta-glucan. A polysaccharide peptide
(PSP), isolated from a strain of Coriolus versicolor
in China, has also been widely used as an anti-cancer
and immunomodulatory agent. Although the mechansim of
their antitumor action is still not completely clear,
these polysaccharides and polysaccharide-protein complexes
are suggested to enhance cell-mediated immune responses
in vivo and in vitro and act as biological response
modifiers. Potentiation of the host defense system may
result in the activation of many kinds of immune cells
that are vitally important for the maintenance of homeostasis.
Polysaccharides or polysaccharide-protein complexes
are considered as multi-cytokine inducers that are able
to induce gene expression of vaious immunomodulatory
cytokines and cytokine receptors. Some interesting studies
focus on investigation of the relationship between their
structure and antitumor activity, elucidation of their
antitumor mechanism at the molecular level, and improvement
of their various biological activities by chemical modifications.
Publication Types: PMID: 10702635, UI: 20169495
Physiol Behav 1997 Mar; 61(3):399-410
Effects of lentinan on abnormal ingestive behaviors induced by tumor necrosis factor.
Tamura R, Tanebe K, Kawanishi C, Torii K, Ono T, Department of Physiology, Faculty of Medicine,
Toyama Medical and Pharmaceutical University, Japan.
Lentinan (LNT), a beta-glucan derived from Lentinus edodes (Berk.) Sign., is known to
work positively against cachexia in patients with malignant tumors. Because the cachectin/tumor
necrosis factor (TNF) is supposed to be one of the factors that mediate cancer cachexia,
we tested the effects of LNT on TNF-induced cachexia in rats. First, we analyzed in detail
the cachectic actions of TNF (0.2 mg/kg/day, 5 days, IV) on food and water intake, body
weight, and locomotor activity. The day after the first administration of TNF (acute phase),
food and water intake, as well as body weight, of all rats decreased. However, over the
next few days of treatment (chronic phase), the rats gradually developed a tolerance to
the cachectic actions of TNF. Specifically, after the third administration, the rats treated
with TNF had a higher amount of water intake than the control rats. This was mainly due
to an increase in daytime water intake. We also analyzed the effects of LNT (0.1 or 1.0
mg/kg, twice/wk. IV) on TNF-induced cachexia, and compared the data with those from the
rats treated with TNF alone. The higher dosage of LNT significantly suppressed TNF-induced
daytime polydipsia and increased the amount of nighttime water intake, as well as the meal
size of nighttime food intake. These results suggest that LNT partially normalizes TNF-induced
cachexia in rats. PMID: 9089759, UI: 97245000
|
