Immune Fx
References and Research Articles
AGARICUS BLAZEI
Biotherapy 1998; 11 (4):259-65 …
Antitumor effect of a peptide-glucan preparation extracted from Agaricus blazei in a double-grafted
tumor system in mice.
Ebina T, Fujimiya Y, Division of Immunology, Miyagi Cancer Center Research Institute, Natori,
Miyagi, Japan.
The antitumor effect of extracts obtained from the fruit body of Agaricus blazei Murill
was examined in a double-grafted tumor system, in which BALB/c mice received simultaneous
intradermal injections of Meth-A tumor cells in both the right (10(6) cells) and left flank
(2 x 10(5) cells), and were then injected with 5 mg of extracts of A. blazei in the right
tumor on days 3, 4 and 5. Intratumoral administration of ethanol-soluble (Fraction 1), water-ethanol-soluble
(Fraction 2), ammonium oxalate-soluble (Fraction 3) and ammonium oxalate-insoluble (Fraction
4) fractions resulted in inhibition of tumor growth, with Fraction 3 showing the most tumoricidal
activity, producing regression of the right tumor and inhibition of growth of the left,
non-injected tumor. The maximum effect was obtained using 0.5 mg of Fraction 3 and this
amount was used in subsequent experiments. The antitumor effect of intratumorally administered
Fraction 3 was enhanced by oral ad lib administration of feed containing 0.083% of Fraction
3. When immunized spleen cells from mice that had been cured by intratumoral administration
of 0.5 mg of Fraction 3 were directly injected (2 x 10(7) cells/mouse) into the Meth-A tumor,
tumor growth was inhibited. The tumor cells on day 7 from the Fraction 3-treated right tumor
and from the left tumor were cultured for 24 h and their culture supernatants were assayed
for neutrophil or macrophage chemotactic activity. Significant macrophage chemotactic factor
activity was detected in the culture media from the left tumor tissue. Serum levels of immunosuppressive
acidic protein (IAP), produced by activated macrophages and neutrophils, increased transiently
soon after intradermal injection of 0.5 mg of Fraction 3. These results suggest that regression
of the left non-injected tumor was due to an immune reaction, involving induction of cytotoxic
cells in the spleen, and the release of chemotactic factors in the distant tumor. PMID:
9950102, UI: 99133601
Cancer Immunol Immunother 1998 May; 46(3):147-59 ...
Selective tumoricidal effect of soluble proteoglucan extracted from the basidiomycete, Agaricus
blazei Murill, mediated via natural killer cell activation and apoptosis.
Fujimiya Y, Suzuki Y, Oshiman K, Kobori H, Moriguchi K, Nakashima H, Matumoto Y, Takahara
S, Ebina T, Katakura R, Division of Immunology, Miyagi Cancer Center Research Institute,
Natori, Japan.
We have isolated a novel type of natural tumoricidal product from the basidiomycete strain,
Agaricus blazei Murill. Using the double-grafted tumor system in Balb/c mice, treatment
of the primary tumor with an acid-treated fraction (ATF) obtained from the fruit bodies
resulted in infiltration of the distant tumor by natural killer (NK) cells with marked tumoricidal
activity. As shown by electrophoresis and DNA fragmentation assay, the ATF also directly
inhibited tumor cell growth in vitro by inducing apoptotic processing; this apoptotic effect
was also demonstrated by increased expression of the Apo2.7 antigen on the mitochondrial
membranes of tumor cells, as shown by flow-cytometric analysis. The ATF had no effect on
normal mouse splenic or interleukin-2-treated splenic mononuclear cells, indicating that
it is selectively cytotoxic for the tumor cells. Cell-cycle analysis demonstrated that ATF
induced the loss of S phase in MethA tumor cells, but did not affect normal splenic mononuclear
cells, which were mainly in the G0G1 phase. Various chromatofocussing purification steps
and NMR analysis showed the tumoricidal activity to be chiefly present in fractions containing
(1-->4)-alpha-D-glucan and (1-->6)-beta-D-glucan, present in a ratio of approximately
1:2 in the ATF (molecular mass 170 kDa), while the final purified fraction, HM3-G (molecular
mass 380 kDa), with the highest tumoricidal activity, consisted of more than 90% glucose,
the main component being (1-->4)-alpha-D-glucan with (1-->6)-beta branching, in the
ratio of approximately 4:1. PMID: 9625538, UI: 98287220
Biochem Mol Biol Int 1999 Apr; 47(4):707-14
Anti-tumor polysaccharide from the mycelium of liquid-cultured Agaricus blazei mill.
Mizuno M, Minato K, Ito H, Kawade M, Terai H, Tsuchida H, Graduate School of Science and
Technology, Kobe University, Japan.
Anti-tumor active polysaccharide against Sarcoma 180 was isolated by DEAE-Sepharose CL-6B
and Sepharose 4B column chromatography from the hot-water soluble fraction of the mycelium
of liquid-cultured Agaricus blazei mill. This polysaccharide did not react with antibodies
of anti-tumor polysaccharides such as lentinan, gliforan, and FIII-2-b which is one of anti-tumor
polysaccharides from Agaricus blazei. Moreover, the analyses of 13C-NMR and GC-MS suggested
that this polysaccharide was preliminarily glucomannan with a main chain of beta-1,2-linked
D-mannopyranosyl residues and beta-D-glucopyranosyl-3-O-beta-D-glucopyranosyl residues as
a side chain. This polysaccharide was completely different from the anti-tumor polysaccharide
from fruiting body of Agaricus blazei, beta-1,6-glucan.
PMID: 10319424, UI: 99252982
Anticancer Res 1999 Jan-Feb; 19(1A):113-8
Tumor-specific cytocidal and immunopotentiating effects of relatively low molecular weight
products derived from the basidiomycete, Agaricus blazei Murill.
Fujimiya Y, Suzuki Y, Katakura R, Ebina T, Division of Immunology, Miyagi Cancer Center
Research Institute, Natori, Japan.
Currently, some natural herbal extracts are believed to have a marked tumoricidal effect
and low toxicity for normal tissues. We investigated the effect of relatively low molecular
weight products extracted from the basidiomycete, Agaricus blazei Murill, on MethA tumor
cell growth with the aim of producing synthetic derivatives based on these products. Inoculation
of the low molecule fraction (LM) into the primary tumor of a two-tumor model resulted in
the marked inhibition of the tumor, not only in the right flank, but also in the non-injected
left flank. Chromatographic purification and physicochemical characterization showed the
main tumoricidal activity to be located in a low molecule fraction-3 (LM-3), containing
alpha-1,4-glucan-beta-1,6-glucan complex with an average molecular weight of 20 kDa. A11
LM fractions and crude ATF showed in vitro selective cytotoxicity for MethA tumor cells,
having no effect on normal cells. Serum levels of immunosuppressive acidic protein (IAP)
in mice receiving LM fractions, particularly LM-3, significantly increased indicating the
possible activation of granulocytes. We speculate that the inhibition of the distant tumor
might be due to the increased migration of granulocytes, enhanced by the effect of extract
injections at the primary tumor site. PMID: 10226531, UI: 9924311
Biosci Biotechnol Biochem 1998 Mar; 62(3):434-7
Polysaccharides from Agaricus blazei stimulate lymphocyte T-cell subsets in mice.
Mizuno M, Morimoto M, Minato K, Tsuchida H, Division of Science of Biological Resources,
Graduate School of Science and Technology, Kobe University, Japan.
Subset analysis of splenic lymphocytes using flow cytometry showed that the percentages
of Thy1.2-(pan T-cells), L3T4-(CD4, helper T-cells), and Lyt2-(CD8, cytotoxic T-cells) positive
cell populations were significantly increased in mice orally administered a hot water-soluble
fraction from Agaricus blazei as compared with mice treated only with saline. 13C-NMR data
indicates that the main component in the active polysaccharide is the complex of alpha-1,6-
and alpha-1,4-glucan, which had already been shown to have anti-tumor activity against Sarcoma
180. It seems that the polysaccharide from Agaricus blazei may be an effective prophylactic,
protecting humans against cancer by stimulating lymphocytes such as cytotoxic T-cells. PMID:
9571772, UI: 98233265
Nippon Yakurigaku Zasshi 1997 Oct; 110 Suppl 1:98P-103P
A stable culturing method and pharmacological effects of the Agaricus blazei.
[Article in Japanese]
Higaki M, Eguchi F, Watanabe Y, Lab. of Forest Products Chemistry, Tokyo University of Agriculture,
Japan.
There have been some reports suggesting the effectiveness of medicinal mushrooms in not
only keeping health but also preventing and curing diseases as well as recovering from illnesses.
However, no uniformity has been observed with its medicinal effect and thus there are some
problems in these materials from clinical aspects. Ununiformity of constituents which has
resulted from the lack of established optimum culturing methods and inadequacy of experimental
approaches are given as the causes of the problems. In the present study, the authors established
a culturing method for harvesting fruit bodies with stable constituents by the use of the
best cytogenetical technique for Agaricus blazei(CJ-01)which has attracted special interest
recently among medicinal mushrooms. Fundamental medical scientific researches have been
conducted with the medicinal effect of Agaricus blazei(CJ-01)obtained by the new culturing
method by the widely use of immunological and pharmacological approaches. Based on the results
of these studies, the author demonstrated the effect scientifically on the cases where the
effect had already been observed clinically (hypertension, atopic dermatitis and diabetes).
PMID: 9503414, UI: 98164155
Jpn J Pharmacol 1994 Oct;66(2):265-71
Inhibitory action of a (1-->6)-beta-D-glucan-protein complex (F III-2-b) isolated from
Agaricus blazei Murill ("himematsutake") on Meth A fibrosarcoma-bearing mice and
its antitumor mechanism.
Itoh H, Ito H, Amano H, Noda H, Laboratory of Marine Biochemistry, Faculty of Bioresources,
Mie University, Japan.
The effects of F III-2-b (Agaricus blazei Murill polysaccharide) with or without 5-fluorouracil
(5-FU) on immune responses were investigated in Meth A tumor-bearing and normal mice. The
i.p. administration of F III-2-b (10 mg/kg/day x 30) moderately inhibited the growth of
Meth A tumor cells implanted s.c. in mice. Development of implanted tumors was strongly
inhibited by the combination of F III-2-b and 5-FU. The picryl chloride-induced delayed
type hypersensitivity (PC-DTH) response in mice was depressed after the implantation of
tumor and treatment with 5-FU. F III-2-b restored the suppression of PC-DTH by 5-FU, but
did not increase the PC-DTH of normal mice. F III-2-b not only enhanced the degree of spleen
cell-mediated sheep red blood cells (SRBC) hemolysis (quantitative hemolysis of SRBC), the
indexes of the spleen and thymus, and the number of spleen cells but also restored the suppressive
effect of 5-FU. In the group receiving F III-2-b, the percentages of splenic Thy1.2-, L3T4-
and asialo GM1-positive cells were significantly increased as compared with the tumor-bearing
mice treated with saline. Furthermore, the L3T4+/Lyt2+ ratio showed a tendency to increase,
and the Lyt2+ ratio was markedly decreased. These results suggest that the antitumor effect
of F III-2-b may be correlated with the changing pattern of the Thy1.2-, L3T4- and asialo
GM1-positive cells. PMID: 7869611, UI: 95174220
Yakugaku Zasshi 1994 May;114(5):342-50.
Antimutagenic and bactericidal substances in the fruit body of a Basidiomycete Agaricus
blazei, Jun-17.
[Article in Japanese] Osaki Y, Kato T, Yamamoto K, Okubo J, Miyazaki T, Tokyo College of
Pharmacy, Japan.
The fruit body of a Basidiomycete Agaricus blazei, Jun-17 (Himematsutake) was extracted
with hexane and chloroform-methanol (2:1, v/v), and the antimutagenic effect of the extracts
was examined using an Ames/Salmonella/microsome assay. Both extracts of Agaricus inhibited
the mutagenicity of benzo[a]pyrene(B[a]P). The hexane extract was purified by silica gel
column chromatography and high performance liquid chromatography (HPLC), and linoleic acid
was isolated as a main substance having antimutagenic activity. Fr. IIa, IIb, IIc and IIb,
which reduced the number of His+ revertant colonies induced by B[a]P, were separated from
the chloroform-methanol extract by silica gel column chromatography and HPLC. An antimutagenic
substance in Fr. IIa was linoleic acid. From Fr. IIb, a bactericidal, not antimutagenic,
substance was isolated and identified as 13-hydroxy cis-9, trans-11-octadecadienoic acid
(13ZE-LOH). Antimutagenic substances in Fr. IIc and IId were not purified. The possible
source and mechanism of formation of 13ZE-LOH are discussed. PMID: 8014843, UI: 94285038
Carbohydr Res 1988 Nov 15; 183(1):150-4
Isolation and properties of a lectin from the fruiting bodies of Agaricus blazei.
Kawagishi H, Nomura A, Yumen T, Mizuno T, Hagiwara T, Nakamura T, Department of Agricultural
Chemistry, Faculty of Agriculture, Shizuoka University, Japan. PMID: 3233595, UI: 89168256
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