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The Agaricus blazei Murill (AbM), also known as Agaricus brasiliensis L. due to its origin in Brazilian rain forest, is an edible mushroom of the Basidiomycetes family, which also comprises medicinal mushrooms such as Hericium erinaceus and Grifola frondosa. AbM has been used in traditional medicine locally and also recently as a health food worldwide. Since it has been found to possess immunomodulatory properties, its biological and health-related effects, as well as its isolated active ingredients e.g. beta-glucans, have been examined by scientists. Otherinvestigations have been performed with mixed mushroom products, such as AndoSanTM, which contains mostly AbM, but also the two other mushrooms above. AbM-related benefits reviewed here include effects against cancer, infections, inflammation, allergy/ asthma and diabetes. Effects of AndoSanTMand other AbM-based extracts have been compared in a bacterial sepsis model.
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Review Open Access
Agaricus blazei Murill - immunomodulatory properties and health benefits
Biedron R1,2, Tangen JM3, Maresz K1, and Hetland G4
1International Science and Health Foundation, Cracow, Poland, 2Department of Immunology,
Jagiellonian University Medical College, Cracow, Poland, and 3Departmentts of Hematology and
4Cellular Therapy, Oslo University Hospital, Oslo, Norway
Correspondence: Geir Hetland, MD, PhD, Department of Cellular Therapy, Oslo University
Hospital, Oslo, Norway
Submission date: August 27, 2012, Acceptance date: November 15, 2012; Publication date:
November 17, 2012
Abstract
The Agaricus blazei Murill (AbM), also known as Agaricus brasiliensis L. due to its origin in
Brazilian rain forest, is an edible mushroom of the Basidiomycetes family, which also comprises
medicinal mushrooms such as Hericium erinaceus and Grifola frondosa. AbM has been used in
traditional medicine locally and also recently as a health food worldwide. Since it has been found
to possess immunomodulatory properties, its biological and health-related effects, as well as its
isolated active ingredients e.g. beta-glucans, have been examined by scientists. Other
investigations have been performed with mixed mushroom products, such as AndoSanTM, which
contains mostly AbM, but also the two other mushrooms above. AbM-related benefits reviewed
here include effects against cancer, infections, inflammation, allergy/ asthma and diabetes.
Effects of AndoSanTM and other AbM-based extracts have been compared in a bacterial sepsis
model.
Keywords: Agaricus blazei, AndoSanTM, allergy, asthma, cancer, infection, inflammation,
immunomodulation.
Introduction:
From the very beginning of our civilization, man has used mushrooms to produce fermented
foods and medicines. In ancient Egypt, fermentation was considered a gift from the gods, just
like in ancient Rome. Asians have attributed curative properties to mushrooms, and there are
Chinese reports from around 500 BC on the general medicinal and anti-cancer properties of
Ganoderma extracts which have been passed on from generation to generation. In the late
twentieth century, researchers in Japan demonstrated the beneficial effects of a Brazilian
mushroom, later identified as Agaricus blazei Murill (AbM), which quickly gained attention in
the scientific world [1, 2].
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Agaricus blazei Murill (Cogumelo de Deus), which means "fungus from God”, is an edible,
medicinal mushroom originally found in a small village of Piedade, in the mountain region near
São Paulo, Brazil. The absence of serious disease in the elderly, and the longevity in the
population surprised researchers who found that this was due to AbM being a part of the diet of
this healthy local population.
AbM has traditionally been used for the prevention of cancer. Its putative anti-tumorgenic
effects have sparked the interest of scientists who decided to put AbM through rigorous scientific
scrutiny. A series of laboratory studies gathered from all over of the world have demonstrated
anti-cancer properties of AbM and its impact on the immune system [3-10]. AbM is also used to
treat a wide variety of diseases including chronic hepatitis [11, 12], allergies [13], and asthma
[14].
AbM contains large quantities of polysaccharide compounds like β (beta) -1,6-glucan [7],
alpha-1,6- and alpha-1,4-glucan [15], glucomannan [16], β -1,3-glucan [8] and more. Beta-
glucans are quite diverse in size and structure and thus possess varied immunomodulating
abilities. Data from in vitro studies and animal models indicate that AbM extracts bring about
positive effects in different disease models. They boost the immune system by activating white
blood cells, including “immune directors”, and thus enhancing its action against cancer [3, 4, 7,
16-19] and infection [12, 20-23]. These immune-enhancing effects on the activity of
macrophages and natural killer (NK) cells, lead to the destruction of microbes and tumor cells
much more efficiently, not only through innate immunity, but also adaptive immunity by the
activation of dendritic cells, and in consequence, engagement of specialized lymphocytes [24,
25]. Recently, AbM extracts were used in conjunction with traditional classical cancer
treatments, such as chemotherapy [26], which similar to X-irradiation of tumors, have many
undesirable side effects that degrade the quality of life. AbM could prove valuable in easing side
effects and thus improving the quality of life for cancer patients [26]. Careful clinical studies
comparing the activity of isolated compounds from whole mushroom extracts and
epidemiological data are still necessary to determine whether AbM offers real clinical benefits.
Besides beta-glucans and proteoglucans, there are undoubtedly other substances in this
mushroom with direct health-promoting properties. As time and research go on, it has become
more and more certain that AbM can serve as a support for patients of today with different
diseases as a supplemental treatment to Western medicine, and not only be regarded as a remedy
in traditional medicine.
The immune system our defense mechanism system
The immune system is comprised of a collection of molecules, cells, and organs whose complex
interactions form an efficient system that is usually able to protect an individual from both
outside invaders and its own altered internal cells, e.g. cancer cells. When the immune system
works properly, humans remain healthy. However, the immune system in many people is
weakened by stress, poor eating habits and a multiplicity of pollutions in air, water and food.
With an immune system in disarray, affected people can suffer from a number of diseases.
The immune system is supported by signal molecules such as cytokines. including the
interferons and chemokines among others, that are essential to the immune system as they induce
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an antimicrobial state in other cells. These signaling chemicals are secreted by various
leukocytes responsible for activating other cells, coordinating, and regulating important
biological processes such as inflammation [27]. Inflammation is an immune defense response; it
results in quicker blood flow, increased temperature and finally, attraction of immune cells to the
threatened area [27]. Inflammation can be caused by microbial infections and physical agents
causing tissue injury. The function is to destroy invaders and induce tissue repair and healing.
The elements of the immune system are divided it into two functionally distinct parts: the
innate and the adaptive (acquired) immune systems. It is apparent that these two groups are in no
way isolated; a complex dialog is constantly going on between them [28]. The numerous
cytokines that are produced, and the array of surface molecules that are expressed in response to
external or internal threats, are critical for the control of all other immune elements and their
concerted action [29]. The dendritic cells, which can be of myeloid or lymphocytic origin, are
directors of the entire immune system.
T-cells are one of the most important elements in the human adaptive immune system. Their
role is in directly destroying infected or cancerous cells, giving help to develop antibody-
producing cells and in maintaining memory in so-called memory cells that live for years and can
recognize former microbial attackers. Whereas dendritic cells are the directors of the entire
immune system, T helper cells represent the local control center for the adaptive immune system
[30, 31].
Many other cell types, including macrophages, NK cells, and B-cells are important in the
“effector phase” of the immune response [30, 32].
The innate immune system
The innate immune response functions as a first line of defense against infections. It consists of
soluble factors, such as complement proteins, and diverse cellular components of the myeloid
linage; granulocytes, monocytes/macrophages, dendritic cells and mast cells, as well as natural
killer (NK) cells [27, 28, 30, 33]. Macrophages (“grand eaters”) and dendritic cells are important
regulators of immune responses through their uptake of foreign elements, digestion of them, and
presentation of smaller bits of these so-called antigens to T cells. This antigen presentation is a
critical determinant of the degree of T-cell activation, and contributes to the T-cell’s ability to
discriminate between self-cells and foreign antigens [33]. Granulocytes,
monocytes/macrophages, and NK cells are responsible for killing invaders, function as key
innate effector cells, and facilitate communication by releasing important chemo-attractants [27].
In contrast to the above non-specific effectors, NK cells have a specific function in their killing
of infected and cancerous cells. Unfortunately, their mode of action is restricted to attacking only
cells to which they have been previously exposed. They play a significant role because they are
an important first line of defense against malignant cells and cells infected with viruses, bacteria,
and protozoa. Like monocytes and granulocytes, NK cells produce signal substances, cytokines
that activate and regulate other immune elements with specific receptors on their surfaces, for
such cytokines. In addition, they independently handle the destruction of tumor cells [10, 34].
The adaptive immune system
The adaptive immune system is composed of highly specialized, systemic cells and processes
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that eliminate or prevent pathogenic challenges. It is also able to distinguish foreign cells from
self, and can distinguish one foreign antigen from another. While a macrophage will engulf any
foreign cell (and many destructed self-cells), adaptive immune cells have mechanisms for
selecting only a precisely defined target. A specific feature of the adaptive immune system
enables immunization and resistance to reinfection, from the same microorganism [30].
The cells which make up the immune system are the lymphocytes, of which there are two
main sub-populations: B cells and T cells. The lymphocytes originate in the bone marrow. The T
lymphocytes are “educated” in the thymus to distinguish between own and foreign antigens
(processed bits of bacteria, cells etc).
Lymphocytes are developed from stem cells in the bone marrow. Some migrate to the
thymus and develop into T lymphocytes (or T cells), while others remain in the bone marrow and
develop into B lymphocytes (or B cells). Both B- and T-cells then migrate to lymphoid tissue
such as lymph nodes. B cells are most effective against invading bacteria and their toxins, while
T cells recognize and destroy body cells gone awry, including virus-infected cells and cancer
cells [27, 32]. T cells also give help to develop the B cell-derived antibody-producing plasma
cells.
Figure 1. T helper (Th) cells are divided into Th1 cells that normally have anti-infection and
anti-tumor effects, and Th2 cells that normally have anti-parasitic and anti-rejection (e.g. of fetus
during pregnancy) effects. There are also interacting T-regulatory cells and Th17 cells, which
control the Th1 and Th2 responses. The cellular interaction is done by cytokines, which promote
(→) or inhibit (---I) T cell differentiation and activation.
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Whenever T cells are activated, some of them become "memory" cells. Then, the next time
that an individual encounters that same antigen, the immune system is ordered to destroy it
quickly. The degree and duration of immunity depend on the kind of antigen, its amount, and
how it enters the body. An immune response is also dictated by heredity; some individuals
respond strongly to a given antigen, others weakly, and some not at all [30, 34].
T cells break down into two crucial sub-populations: T helper cells (Th) and cytotoxic
(killer) T cells (CTL). Th cells are crucial because they are engaged in activating B cells and
macrophages. This is a perfect example of immune system cooperation. CTL on the other hand,
act by killing virus infected cells. A schematic illustration is shown in Fig. 1 of the balance
between T cell responses in adaptive immunity and the resulting effect on health threats as well
as the different T cell responses (blue text). The overall function of lymphocytes may be divided
into i) B cells that are effectors of the humural immune response through antibody production,
and ii) T cells which are effectors of the direct cell-mediated immune response.
Autoimmunity
Autoimmunity is surprisingly common, and amazingly complex. This is an over-reaction of the
immune system and is caused by cross-reactivity - the pathogen seems to look like self-cells,
which are usually ignored because they are not seen in an inflammatory (“danger”) context.
However, the pathogen is seen in such a context and drives the activation and expansion of cross-
reactive T cells that then return home and attack the self-antigen, causing autoimmune disease
that can then expand and become more severe. This is a perfect example of how fragile the
immune system is.
Autoimmunity may arise in several ways. Firstly, by a reduction in suppressor T cell (T
regulatory cell) activity; secondly, due to the modification of normal self-antigens, by drugs,
environmental chemicals, viruses, or mutations; and thirdly, due to an exposure in the direction
of an antigen that is very similar to self-antigen ("molecular mimicry"). This is a good example
of how important it is for the immune system to stay in balance with itself since any imbalance
may cause a threat and might bring about unwanted repercussions [35-38].
Beta-glucans as an active component of Agaricus blazei Murill
Beta-glucans are naturally occurring polysaccharides, which are polymers of glucose with beta
1,3/1,6-linkages, and might be found in the cell walls of algae, bacteria and certain fungi and
mushrooms. They differ in their structure, molecular mass and solubility.
AbM is well-known to contain a high level of beta-glucans in three different forms: β-(1-3)-
D-glucan, β-(1-4)-D-glucan, and β-(1-6)-D-glucan [3, 7, 8, 16]. Research has shown that
insoluble (13/1-6)-β-glucan, has greater biological activity than that of its soluble (1-3/1-4)-β -
glucans counterparts [39]. The differences between β-glucan linkages and chemical structure are
significant in regards to solubility, mode of action, and overall biological activity. Beta-glucans
derived from AbM are known for stimulating immune cells like NK cells, macrophages,
dendritic cells, and granulocytes (polymorphonuclear leukocytes) [3-5, 7, 16, 17].
In addition to beta-glucans, AbM’s effect on the immune system is believed to be the result
of other polysaccharides such as proteoglucans [10]. What is important, is the very high content
of beta-glucans in AbM compared to other mushroom species, and which may be the antitumor
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principle of this mushroom [8]. For instance, its relative - the champignon (Agaricus bisporus) -
has much less beta-glucan and more mannan sugars. In general, the known active compounds of
AbM include: beta-glucans, ergosterol (provitamin D2) derivatives, glucomannan,
mannogalactoglucan, proteoglucans and riboglucans [3, 8, 10, 15-17, 19, 25, 40]. The
polysaccharides’ phyto complex is thought to be responsible for its immune-stimulant and anti-
tumorgenic properties. Kawagishi [7] was the first to isolate active anticancer compounds
purified from the sodium hydroxide extract of the fruit body of AbM. The author detected
polysaccharides with apparent antitumor activity [7]. Current clinical studies are yielding
conformatory results [26, 41], which may need further validation.
It has been scientifically proven that some forms of beta-glucans can play an important role
in human health [42, 43]. They are able to help the immune system because they represent a
common “danger signature” of health-threatening mushrooms and fungi [44-48]. Since harmless
edible mushrooms such as AbM contain high amounts of these beta-glucan danger signals, this
can be exploited by us to enhance the alertness of our immune system for general prevention of
disease and as an additive treatment to help combat existing disease.
Mechanism of action
A healthy and strong immune system is crucial for a healthy body. One of the most important
properties of AbM is the ability to boost immune responses. Immunomodulation might be caused
by a group of extremely efficient immunostimulants such as β -glucans (β -1-3-D-glucans and β-
1-6-D-glucan), which are active constituents of AbM. Glucans activate a number of cells
involved in immune reactions [49, 50]. AbM also contains other smaller uncharacterized
molecules that are important for AbM’s health effects (Hetland G, unpublished findings). A
beneficial effect has been suggested of beta-glucan on generation of new blood cells in the bone
marrow of cancer patients who received such add-on (adjuvant) treatment during chemotherapy
[43]. However, in vitro experiments with bone marrow stem cells indicate that AbM does not
promote such blood stem cell multiplication (Tangen and Hetland, unpublished results).
However, AbM extracts rather enhance innate immunity by targeting and activating the innate
immune cells such as macrophages, monocytes, dendritic cells, granulocytes and NK cells. In
short, this implies that AbM is an activator of these phagocytic cells, including the non-
phagocytic NK cells [24, 26, 48, 49]. In addition, AbM extract stimulates cytokine production,
which is needed for activities of these immune cells. The AbM extract stimulates maturation of
dendritic cells that present antigen/self-antigen complexes that activate T-cells [24, 25, 51].
The reason for this forceful and swift reaction of innate immunity when in contact with an
edible and harmless mushroom such as AbM, is its shearing of pathogen-associated molecular
patterns (PAMP) with other highly poisonous and health-threatening fungi and mushrooms.
PAMP, such as beta-glucans form the main cell wall skeleton in mushrooms and fungi and are
recognized immediately by so-called pattern-recognition receptors, such as Toll-like receptor 2
(TLR2), dectin-1 and complement receptor 3 (CR3) [48, 52-54]. When these receptors are
engaged, signals are transmitted into the immune cells, stimulating them to produce and release
biologically active mediators such as cytokines [24] that are signal substances needed in the
communication with other immune cells, and nitric oxide and hydrogen peroxide [55] that
directly kills invading microbes. Since AbM does not have a direct bacteria-killing effect, its
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action on bacterial sepsis is via modulation of cells and a cascade defense like the complement
system, an important part of the innate immune system [56].
Health Benefits of Agaricus Blazei Murill
Cancer
Cancer is a disease which is characterized by uncontrolled cell growth (a division beyond normal
limits), and is the leading cause of death in Western countries. Cancer may affect people at all
ages and genders. The risk for most types of cancer increases with age, and is primarily impacted
by environmental factors with a 90-95% of cases influenced by lifestyle and environmental
factors and 5-10% due to genetics [57].
It has been shown that a significant number of cancer patients have been taking
complementary medical therapies such as medicinal mushrooms, while receiving their
conventional anti-cancer treatments. Mushroom extracts have been proposed to have anti-cancer
properties and may act through two separate mechanisms: i) direct cytotoxic effect and ii)
indirectly through immunomodulatory action [50].
The orally administered β-glucans were taken up and processed by macrophages via surface
receptors such as Dectin-1 with or without TLR-2/6, and complement receptor (CR)-3, eliciting
an immune response. One of the actions is the phagocytosis of antibody-tagged tumor cells [1].
Another direct consequence of AbM treatment in cancer patients, and possibly brought about by
the mushroom’s beta-glucans, is activation of the patients NK cells. Studies found that a group
of active ingredients such as beta-glucans, proteoglycans and ergosterol were responsible for the
induced tumor regression in mice [3, 8, 10, 15-17, 25, 40]. Additionally, mice which were
supplemented daily with beta-glucan isolated from AbM, exhibited a decreased level of
spontaneous metastasis [58]. In another set of experiments, fat soluble ergosterol from AbM
proved to be an antiangiogenetic substance, which hampers blood vessel formation and as a
result, reduces tumor growth and metastasis in sarcoma- and lung carcinoma- bearing mice [59].
Another action of AbM in this context, is the reduction in blood levels of IL-8, an inflammatory
and vessel-forming cytokine.
The antitumor effects of AbM extracts have been attributed to the induction of apoptosis
(programmed cell death) of cancer cells and the activation of NK cells [9, 10]. It has been
reported that increased NK cell activity correlates with increased infiltration of cells in tumor
sites. Moreover, the analysis of leukocytes from hepatitis C virus (HCV) patients supplemented
with AbM extracts, revealed an increased expression of genes, which are crucial in antitumor
defense [11]. One early clinical trial focused on patients with acute leukemia and demonstrated
that extracts from AbM inhibited leukemia cells [60]. However, there are no published follow-up
studies on the use of AbM against leukemia.
At the moment, AbM is used as adjuvant treatment alongside traditional treatments for
cancer. AbM could prove valuable in both its antitumor effects via immune stimulation and in
easing side effects and thus improving the quality of life for cancer patients as seen in one
clinical study [26]. The effect of AbM on prostate cancer has been unequivocal [9, 61]. AbM, in
a mixture with other medicinal mushrooms, has also been reported to act against breast cancer
cells in vitro [62]. However, more clinical trials are needed to confirm this mechanism of action.
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In addition to AbMs induction of apoptosis in some cancer cell types, its immunomodulatory
role against cancer, is shown in Fig. 2.
Research in progress
Currently, there are some ongoing animal and clinical studies, which are focused on the role of
AbM extracts in treating cancer.
Colon cancer is a cancer of the large intestine (colon), the lower part of the digestive system.
Rectal cancer is a cancer of the last several inches of the colon. When occurring together they are
often referred to as colorectal cancers. Most cases of colon cancer begin as small, noncancerous
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“lumps” of cells called polyps. Over time, some of these polyps may become colon cancers.
A scientific study was performed in Oslo, Norway in the last year, with an AbM-based
extract, AndoSanTM, in a mouse model, which had the same genetic defect as most common
predisposing conditions of human colon cancer; this data is now being examined. If it comes out
positive, a clinical study in cancer colon patients will follow to determine whether AbM can have
a preventive effect on the development of colon cancer in individuals prone to this disease.
Multiple myeloma (from Greek myelo-, bone marrow) is uncontrolled clonal proliferation in
the bone marrow of plasma cells that are derived from B cells. Plasma cells are normally
responsible for the production of specific antibodies which help fight infections. In multiple
myeloma, the multiplicating clone of abnormal plasma cells produces large amounts of
monoclonal antibodies, which can be detected in blood and urine. Health problems caused by
multiple myeloma can affect bones through osteolytic lesions, the immune system, kidneys, and
red blood cell count. The number of new cases of multiple myeloma each year in Western
Europe is approximately 4 per 100,000 inhabitants [63]. Myeloma is an incurable disease
although treatment may help control symptoms and complications and prolong life. The
condition is usually progressive and fatal. Symptoms include anemia, renal damage, and
increased susceptibility to bacterial infections. Treatment options include local irradiation of
myelomas in bone, high-dose chemotherapy followed by stem cell transplantation, and use of
new drugs (e.g. lenolidamide).
A clinical study has been done on multiple myeloma in Norway. The trial enrolled 33
patients, who were treated for 7 weeks with the AbM extract (AndoSan™) or with placebo only
[http://clinicaltrials.gov/ct2/show/NCT00970021]. The supplementation was tested in a double
blinded fashion as adjuvant treatment to high-dose chemotherapy followed by transplantation of
preharvested autologous hematopoietic stem cells that had been mobilized from bone marrow to
peripheral blood. The data will be examined at end of 2012, after the code is broken and
depending on who got the AbM extract and who got placebo. A similar multi-center study may
ensue, pending a positive outcome of the first trial.
Unfortunately, a general cure for cancer is still yet to be found, although 2 out of 3 cancer
patients can today be treated successfully. Currently, even though there are therapies that induce
tumor regression, many people turn to alternative treatment methods. However, it is essential not
to discontinue standard methods of treatment until thorough scientific validation of alternative or
complementary therapies exist.
Gastro-inflammation
The digestive system plays an important role in the human body by absorbing food nutrients into
the blood stream. Uncontrolled intestinal inflammation may lead to different forms of intestinal
disorders called Inflammatory Bowel Disease (IBD). The etiology of these inflammatory
diseases is unknown, but they are assumed to be autoimmune disorders.
IBD refers to two chronic diseases: Ulcerative Colitis (UC) and Crohn's disease (CD).
Although the diseases have some common features, there are important differences. UC is an
inflammatory disease of the large intestine or colon. CD most commonly affects the last part of
the small intestine and parts of the large intestine. The present treatment of IBD contains anti-
inflammatory drugs to decrease the inflammation, and immunosuppressive agents to inhibit the
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immune system from destroying the body's own cells and whole tissues. However, alternative
treatments are becoming more popular each year because of the lack of effective treatment.
Today, costly novel treatment with antibody to the inflammatory cytokine, tumor necrosis factor
(TNF), is used against CD, but this therapy is hampered with development of therapy-resistance
and huge potential side effects.
Recently, AbM has been tested in a clinical trial in Norway on patients with IBD. Clinical
data revealed that patients with UC and CD exhibited a down-regulated level of pro-
inflammatory cytokines such as TNF in the serum as an indication for the local effect in the
colon wall itself. This is an indication of the potential effectiveness of AbM to inhibit the
production of pro-inflammatory cytokines, and reduce calprotectin (a marker for IBD) in UC and
CD patients. Twelve patients diagnosed with UC and 12 patients with CD, volunteered to
participate in the study of oral intake of a normal dose of AndoSan™; 20 ml thrice daily for 12
days. The collected data demonstrated a reduction in several cytokines (especially pro-
inflammatory and chemotactic cytokines) in the serum of UC and CD patients after 12 days of
intake of a Basidiomycetes mushroom extract (AndosanTM) mainly based on AbM. In patients
with UC, there was also a concomitant reduction in levels of fecal calprotectin [41]. Similar
results showing such a decline in levels of inflammation-driving cytokines, have been
demonstrated in healthy volunteers consuming AndoSan™ in a similar experimental set-up [64].
Collectively, the findings support the notion of a general anti-inflammatory and stabilizing effect
of the AbM extract on cytokine release in individuals with good health or IBD. Moreover, the
consumption of this AbM-based medicinal mushroom extract by the IBD patients resulted in no
side effects. Rather, the patients spontaneously reported less bowel problems and joint pain
(common in CD) [41]. Presently, a follow-up placebo-controlled and blinded clinical trial is
being conducted in 100 IBD patients at Oslo University Hospital.
There is no known cure neither for UC nor for CD, which is why alternative therapies are
popular among this group of people. However, it is important to remember that any alternative
treatment should complement, not replace, conventional care.
Hepatitis
The liver is one of the most important organs in our body. Considering all of the liver’s special
functions, and its anatomical location and drainage of blood from the vessels in the bowels, it is
the port of entry (hence the Latin name “Vena porta” for the vein from intestines to liver), of
ingredients and impurities in food and drink. Thus, the liver is frequently exposed to a large load
of intestinal antigens from pathogens (viruses, bacteria, parasites), toxins, tumor cells, and
harmless dietary antigens [65]. Statistics and epidemiological data say that except for alcohol and
drug overdose, the main reason for liver damage is viral infection due to hepatitis, especially B
(HBV) and C (HCV) forms. The liver is a blood-rich organ containing large numbers of
phagocytic cells and NK cells, which can be activated by β-glucans, in addition to Kuppfer cells
relatives of macrophages, and also endothelial cells aligning the sinusoids that can be
stimulated by AbM.
Ongoing clinical studies
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Preliminary data shows clinical effects of the AbM condensed liquid in human volunteers with
an elevated activity of γ-glutamic-pyruvate transaminase (γ-GTP), a marker for liver damage. A
total of 20 patients (half of which were men) with chronic C-type hepatitis received the extract
orally, twice a day, for 8 weeks. Reduced serum γ-GTP levels were established in 80% of the
patients without any toxicological findings or other side effects. It was concluded from these
results that the AbM extract could be useful for patients with C-type hepatitis [66].
An open-label pilot study conducted over a 1 year period, tested whether the AbM extract
can improve liver function in patients with hepatitis B. Four patients under 12 months of clinical
observation with alanine aminotransferase (ALT) over 100 IU/L, and not taking drugs for
hepatitis were given an AbM extract (1500 mg daily for 12 months). The ALT level was taken as
a major outcome measurement. At the end of the study, the levels of both aspartate
aminotransferase (AST) and ALT decreased. This data indicated the potential benefit of the AbM
extract in normalizing liver function of patients with hepatitis B [12].
In other studies, a possible in vivo effect of oral AbM (AndoSanTM) was examined in
patients with Interferon (IFN)-α-resistant chronic hepatitis C virus infection. It was observed that
the viral load was slightly, but not statistically significantly, decreased after 1 week of treatment.
The treatment also up-regulated the gene for IFN-α-receptor, implying that AbM may improve
the effect of IFN-α treatment in patients with chronic hepatitis [11]. However, one report on three
patients with advanced cancers contradicted these studies because it suggested that AbM taken as
supplement, induced liver damage [61].
Until today, there has been no good method to compensate for liver failure, especially when
secondary to chronic hepatitis type infections. However, AbM could be a promising remedy in
hepatitis treatment especially for patients with the IFN- resistant type of the disease.
Allergies and Asthma
Allergies are abnormal immune system reactions to substances that are typically harmless to
most people. In this case, the immune system mistakenly identifies a harmless substance such as
tree pollen, as a dangerous invader, and produces antibodies (specific IgE) as well as many active
“immune activators” against the allergen (Betv1),. In consequence, chemicals released by the
immune system lead to allergy symptoms, such as a hay fever, itchy eyes or skin reactions.
Allergies and asthma often occur together, especially in children where 50% of asthma is
induced by allergies in the airway, The diseases are caused by misdirected inflammatory immune
responses which AbM may help rectify because it has been shown to have positive influence
upon T helper (Th) cell subsets [14, 15].
There are two distinct subsets of Th cells that are different in terms of their cytokine
production and biological function, and their responses are balanced against each other (Fig. 1).
These subsets are Th1 and Th2. Anti-tumor and anti-infection immunity are both due to Th1
responses, which also do promote autoimmune diseases when excessive. Anti-rejection and anti-
parasite immunity is due to Th2 responses, which may also induce IgE-mediated allergies. Th1
and Th2 response is mutually inhibitory, so if Th1 cells are stimulated, Th2 cells are suppressed
[67, 68]. This means that Th1 cell activation with AbM will lead to the inhibition of an antibody-
mediated immune response, and in consequences allergy symptoms (Fig. 1).
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Based on a study with mice, it might be concluded that an AbM extract, may prevent the
development of IgE-mediated allergies when given before allergen immunization [14, 69]. The
extract seems to have a therapeutic effect when given together with or as late as 3 weeks after the
allergen immunization in the mouse model (Fig. 3) [13]. Although one should be careful when
extrapolating animal data to a human setting, three weeks for a mouse equals several months for
a human, suggesting that an established allergy in patients can be reverted. The latter study was
done with AndoSanTM.
In summary, the AbM extract may both prevent allergy and allergy-induced asthma
development and be used as a therapeutic substance against allergy and asthma.
Figure 3. Mice were supplemented either with the AbM-based extract, AndoSanTM or PBS
before OVA immunization, and 26 days later serum was collected for the evaluation of specific
antibodies. Results: The level of IgE anti-ovalbumin were lower in the AbM than PBS treated
groups. Similar results were found if AndoSanTM extract or PBS was given 3 weeks after the
allergen immunization (data not shown on this graph).
Diabetes
Diabetes mellitus can be divided into type I that requires insulin treatment to lower blood sugar
levels by promoting sugar transport into cells, and type II which is insulin-independent. Type I
diabetes is an autoimmune disease with specific destruction of insulin-producing pancreatic beta-
cells that culminates in a state of hypoinsulinemia and hyperglycemia. Type II diabetes is
considered a life style-induced disease caused by unhealthy eating/drinking habits and physical
inactivity,or there is also a hereditary element. The latter type is increasing epidemically world-
wide and is especially seen in inner-city youths, and in people experiencing a rapid improvement
in living conditions, e.g. people emigrating from poorer conditions with high physical demands
in undeveloped countries, to richer, developed countries.
AbM has been shown to reduce blood glucose levels in diabetic rat models [70]. There is
also clinical evidence that AbM combined with anti-diabetic drugs can improve insulin resistance
Functional Foods in Health and Disease 2012, 2(11):428-447 Page 440 of 447
in type II diabetes patients [71]. The authors speculated that an increase in so-called adiponectin
concentration could be the mechanism behind the AbM effect. Another group has suggested that
the AbM’s anti-diabetic effect in diabetic rats is due to AbM’s suppression of oxidative stress and
proinflammatory cytokine production, which then results in improvement of pancreatic beta-cells
mass [72].
Comparison of AbM extracts
There are many different AbM extracts available. Glucans, one of the most active and beneficial
components of AbM, are known to augment immune responses against viral and bacterial
infections, as well as against cancer [52]. It is important to point out that not all available AbM
extracts give the same result because they are prepared by using different mushroom strains and
in accordance to different protocols. Latest reports show that there are various compositions of
beta-glucans in AbM extracts [73], and the concentration of active ingredients in each
component depends on the methods of extraction [70, 74] and on the substrate (rotting woods)
they are grown on.
A scientific study compared the efficacy of the leading products available in the market,
revealing extracts with the strongest anti-infection properties. In order to evaluate antibacterial
efficacy of AbM extracts, five AbM products described as A, B, C, D, E were compared in a
mouse model for deadly pneumococcal (Gram-positive) sepsis. The day before the sepsis was
induced, the mice received similar volumes of AbM extracts orally: Extract described as A,
which was a mixture of 82% AbM, 15% Hericium erinaceum and 3% Grifola frondosa, all
members of the Basidiomycetes mushroom family, appeared to be the only one which had a
statistically significant protective effect [52]. Extract A was the most effective in reducing the
number of bacteria in the blood of the infected mice and increasing the survival rate of the
animals. In another study, using Gram-negative bacteria in mice, the efficacy of AbM extract in
decreasing bacteremia and increasing survival rate was confirmed [29]. One may speculate
whether this is due to the presence of additional biological components and synergies with the
two other Basidiomycetes mushrooms ingredients as well as the protocols for cultivation and
processing methods [52].
Extract A currently represents the AndoSan™ product, which appeared to be the only one
that gave a significant protection to overcome deadly bacterial sepsis. Therefore, this particular
mushroom extract was chosen for studies in other animal models and clinical studies (allergy,
HCV infection, IBD, multiple myeloma, colon cancer). Hence, it may be a choice for prevention
or treatment of different illnesses as an adjuvant.
Safety issues
Many researchers have studied AbM, as well as other medicinal mushrooms for close to 50
years. AbM, cultivated on quality-controlled substrate, does not contain toxic substances and is
an effective supplement with good biological effects [11, 26, 75]. AbM can safely be used alone
or in combination with other treatments for patients, as long as the user is not allergic to
mushrooms as such and possible content of harmful substances such as heavy metals, has been
controlled for and excluded. Laboratory tests showed that AbM extract may modulate and
activate the immune cells in their effort to prevent cancer and assist in regulating a dysfunctional
Functional Foods in Health and Disease 2012, 2(11):428-447 Page 441 of 447
immune system (Fig. 2). The safety of the AbM-based extract, AndoSanTM, was shown both in
healthy volunteers [64], and in patients with HCV infection [11] or IBD [41]. Also, no side
effects have been reported in multiple myeloma patients taking this extract as adjuvant treatment
for 7 weeks. A substantial amount of both in vitro [24, 25, 59, 74, 76-78] and in vivo [4, 10, 11,
26, 41, 52, 66, 79] studies and the presence of similar results, supports the assumed inhibition of
tumor growth and immune system stimulation.
There are contradicting reports regarding the effect of AbM on liver function. There is one
report stating that three patients with advanced cancer who took an AbM supplement, suffered
from severe liver damage [61]. A link between the AbM extract and liver damage was suggested,
although several other factors could not be completely ruled out as the causes of liver damage.
On the other hand, studies on AbM intake in patients with chronic hepatitis C virus infection did
not show any adverse side effects on the liver function [11]. Patients in this study were
administered with the AndoSan™ AbM extract, which proved its non-hepatotoxic properties.
What is more, the intake of AbM in the form of AndoSan™ was tested in healthy volunteers and
patients with IBD. A standardized daily dose of 60 ml of the AbM extract for 12 days, as well as
a high daily dose of 360 ml during each of two days was evaluated in the context of safety [64].
Collected data from healthy volunteers [64] and IBD patients [41] revealed no pathological
effects on hematological parameters including those for liver, pancreatic and renal function.
Conclusions
AbM medicinal mushroom modulates the immune system by binding to receptors such as TLR2,
dectin 1 and CR3 on the innate immune cells; NK cells, monocytes and dendritic cells, which
further communicate with T helper cells and bring about an enhanced Th1 response and
concomitant reduction of Th2 response. This immunomodulation explains the different
beneficial health effects attributed to AbM. In addition, AbM possesses a direct apoptotic
property towards different cancer cells, which together with the raised Th1 response and
antiinflammation, generates the AbM-induced antitumor effect. The resulting decreased Th2
response, together with the anti-inflammatory effect, explains the observed anti-allergic and anti-
asthmatic effects and possibly also anti-diabetic properties of AbM in animal models. Lately,
results from several preliminary studies with cancer cells and animal models have prompted a
series of clinical trials, the results of which may reveal the beneficial effects of AbM as adjuvant
treatment for patients [10-12, 26, 41, 61, 64, 71, 80-82]. This bears promise for exploration of
AbM as a therapeutic regimen in the clinical setting.
List of abbreviations: Agaricus blazei Murill (AbM), alanine aminotransferase (ALT), aspartate
aminotransferase (AST), Complement receptors (CR), Crohn's disease (CD), γ-glutamic-pyruvate
transaminase -GTP), Hepatitis C virus (HCV), Inflammatory Bowel Disease (IBD), interferon (IFN),
natural killer (NK), pathogen-associated molecular patterns (PAMP), T helper cells (Th), Toll like
receptors (TLR), tumor necrosis factor (TNF), Ulcerative Colitis (UC)
Competing interests: Biedron R, Tangen JM and Maresz K have no competing interests.
Hetland G is stock holder in Immunopharma, which aims to develop AndoSanTM into adjuvant
hospital medicine.
Functional Foods in Health and Disease 2012, 2(11):428-447 Page 442 of 447
Authors' contributions: All authors have written and/or contributed to the scientific content of
this review article.
Acknowledgements and Funding: The International Science and Health Foundation
(http://www.ishf.org), Cracow, Poland, and Immunopharma, The Norwegian Institute of Public
Health and Oslo University Hospital, Norway, have contributed with funding and /or human
resources for work reviewed in this article.
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... They have been used to treat gastric cancer (lentinan) and head and neck cancer (schizophyllan), in combination with chemotherapy (Ina et al., 2013;Filipa et al., 2017). In addition, other polysaccharides rich in β-1, 3-D-glucans, β-1, 4-D-glucans, β-1, 6-D-glucans, α-1, 4-D-glucans, α-1, 6-D-glucans, and glucomannan have been isolated from A. blazei; these have been shown to have immunomodulatory and antineoplastic properties (Biedron et al., 2012). ...
... Several studies mentioned that most bioactive polysaccharides isolated from mushrooms are branched or unbranched homopolysaccharides (Biedron et al., 2012;Ina et al., 2013;Filipa et al., 2017), which usually contain long chains of glucose polymer. In our study, most of the mushroom extracts were positive with Molisch's test -a general test for detecting carbohydrates, including monosaccharides, disaccharides, and polysaccharides -indicating that the extracts contained carbohydrates. ...
Article
Several kinds of cultivated or local edible mushrooms exist in northern Thailand. While their nutritional features have been extensively analyzed, the presence of phytochemicals and glycosaminoglycans has yet to be investigated. Thus, in this study, we examined the presence of phytochemicals and glycosaminoglycans from 10 cultivated or local mushrooms: milk white russula, hygroscopic earthstar, log white fungi, log black fungi, shitake mushroom, rosy russula, sajor-caju mushroom, Jew's ear, bolete, and straw mushroom. Phytochemical analysis revealed the presence of carbohydrates, amino acids, and flavonoids in the extracts from most of the mushrooms. We detected glycosaminoglycans in all of the extracts using dimethylmethylene blue (DMMB) dye-binding assay and UVVis spectrophotometry. Hygroscopic earthstar contained the most glycosaminoglycans and sajor-caju mushroom the least. However, we were unable to distinguish the types of glycosaminoglycans, which should be considered for future study. In summary, the phytochemicals found here are crucial non-animal dietary sources of carbohydrates, amino acids, and antioxidants. In addition, the glycosaminoglycans detected in the mushroom extracts in this study potentially offer a non-animal source of glycosaminoglycans that may have clinical applications, apart from their nutritive value.
... In addition, clinical studies in humans have reported the role of A. blazei in reducing the adverse side effects of chemotherapy (Ahn et al. 2004;Okamoto 2007). Furthermore, many studies have reported that this fungus can be used as a healthy food for the prevention of a range of illnesses including diabetes, arteriosclerosis, and chronic hepatitis (Biedron et al. 2012;Varghese et al. 2019). In addition, powdered formulations from A. blazei with proteins, carbohydrates, and unsaturated fatty acids can be used in low-calorie diets and have shown high anti-oxidant activity with high content of tocopherols and phenolic compounds (Carneiro et al. 2013). ...
Chapter
Today mankind confronts a heap of challenges for survival due to the advent of health-related issues, drug resistances, and imbalances in the ecosystems. In the era of technology, man has perpetually been endeavoring to search for diverse biotic components that can potentially be addressing the complicated life troubling issues. In this context, the fungi in general and mushrooms in particular have played an indispensable role in protecting and curing various health problems. Macrofungi or mushrooms are contemplated as biological and genetic resources with high nutritional, medicinal, and biotechnological potential. The interest in mushrooms has cultivated momentously in the last few decades, being promoted by the discovery of a repertoire of chemically disparate biologically active compounds having biopharmaceutical applications arbitrated through defined mechanisms (anti-tumor, anti-inflammatory, anti-cancer, anti-oxidative hepatoprotective, anti-viral, immunomodulating hypocholesterolemic, and anti-bacterial). The escalating knowledge about chemistry, biotechnology, and molecular biology of mushrooms as well as an improvement in screening methods has led to rapid surge in the application of mushrooms for medicinal purposes which in turn, have galvanized the development of several novel mycopharmaceuticals based on mushroom bioprospection. Taking into consideration the importance of mushrooms, this chapter aims to zero in on the nutritive value, functionalities of mushrooms, and potential applications in food industry.
... 11,12 Bioactive and antimicrobial compounds present in mushrooms, such as phenolic compounds, ascorbic acid, ergosterol, polysaccharides, carotenoids, steroids, vitamins, terpenes and quinones, have been identified as antioxidants, nutraceuticals and pharmaceuticals. 13,14 Polysaccharides are another class of bioactive compounds biosynthesized by this fungus. Some studies demonstrate the influence of cultivation practices on the production and quantification of ⊎-glucan in mushrooms. ...
Article
Background The fungus Agaricus subrufescens is grown commercially in China, the United States, Brazil, Taiwan, and Japan among others. However, each country adopts a cultivation system that significantly influences the agronomical parameters and chemical composition of the harvested mushrooms. In this study, the influence of the cultivation process on the content of ergosterol and vitamin D2 was evaluated. Results Four commercial strains of A. subrufescens (ABL 04/49, ABL CS7, ABL 18/01, and ABL 19/01) and two environmental cultivation conditions (in the field and a controlled chamber with the absence of sunlight) were used. Infield cultivation, ABL CS7 and ABL 19/01 strains presented better agronomic parameters, whereas, in a protected environment ABL 19/01, ABL 04/49, and ABL 18/01 demonstrated better performance, respectively. The highest biological efficiency value (64%) was provided by ABL 19/01 strain in a controlled environment. Conclusion The highest content in ergosterol (990 mg kg⁻¹) and vitamin D2 (36.8 mg kg⁻¹) were observed in mushrooms obtained in the field from strain ABL 04/49, which presents reasonable agronomic parameters for cultivation. This article is protected by copyright. All rights reserved.
... Bond formation with PRR accelerates the release of biologically active mediators such as cytokines (TNF , IL-1 and MCP-1, and G-CSF). Cytokines directly kills the invading cells by acting as signal substances that aids interaction with other immune cells, and nitric oxide and hydrogen ( Biedron, Tangen, Maresz & Hetland, 2012 ). ...
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Polysaccharides have been studied, examined and explored for number of decades and a wide range of information has been discovered about the polysaccharides that helps in modifying the immune system and its effectiveness. Natural polymers are available in abundance and bear significant resemblance to constituents of biological ex-tracellular matrices. Polysaccharides from plants such as gums, resins, tannins and mucilage have been put to use for their medicinal properties as well as for innovative dosage forms. Polysaccharides are easily endured by human body and even tend to seize high bioactivity and biocompatibility. There have been various investigations to demonstrate the organizational features of these bioactive elements and result in interfering with the cellular units of host individual. This review manuscript will focus on the immunomodulatory potential of non-conventional natural polysaccharides of microbial and plant origin. These specialized polysaccharides are capable of producing a strong impact on the adaptive-, acquired-, and innate-immune system. This is usually carried out by the interaction between them along with T-cells, leukocytes, monocytes, and most importantly with macrophages. Polysaccharides are capable of enriching and modulating the immune response of the host in response to infections as well as have anti-tumor properties-signifying its importance of getting widely available in countries like Japan(currently) and in India (from historic times).
... Furthermore, mushroom polysaccharides are presented as polysaccharide-conjugate complexes called heteroglucan or polysaccharopeptide (PSP), presenting α(1-4)-and β(1-3)-glycosidic linkages with protein components. For example, extracts isolated from Agaricus blazei contain diverse polysaccharideprotein complexes with different chemical linkages, including β-1,6-glucan, α-1,6-and α-1,4-glucan, glucomannan, and β-1,3-glucan [22]. ...
Article
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Mycomedicine is a unique class of natural medicine that has been widely used in Asian countries for thousands of years. Modern mycomedicine consists of fruiting bodies, spores, or other tissues of medicinal fungi, as well as bioactive components extracted from them, including polysaccharides and, triterpenoids, etc. Since the discovery of the famous fungal extract, penicillin, by Alexander Fleming in the late 19th century, researchers have realised the significant antibiotic and other medicinal values of fungal extracts. As medicinal fungi and fungal metabolites can induce apoptosis or autophagy, enhance the immune response, and reduce metastatic potential, several types of mushrooms, such as Ganoderma lucidum and Grifola frondosa, have been extensively investigated, and anti-cancer drugs have been developed from their extracts. Although some studies have highlighted the anti-cancer properties of a single, specific mushroom, only limited reviews have summarised diverse medicinal fungi as mycomedicine. In this review, we not only list the structures and functions of pharmaceutically active components isolated from mycomedicine, but also summarise the mechanisms underlying the potent bioactivities of several representative mushrooms in the Kingdom Fungi against various types of tumour.
... An alkali soluble linear (1 → 3)-α-D-glucan obtained from Amanita muscaria and its carboxymethylated derivative had been exhibited effective antitumor activities [87]. Agarican, polysaccharide isolated from the mushroom Agaricus blazei has been commercialized and used clinically as antitumor agent [88]. Grifron-D, a branched (1 → 3)-, (1 → 6)-β-D-glucan derived from the mushroom, Grifola frondosa also had been commercialized owing to its effective antitumor activities [27,89]. ...
Article
Mushrooms are renewable natural gift for humankind, furnished with unique taste, flavor and medicinal properties. For the last few decades study of mushroom polysaccharides has become a matter of great interest to the researchers for their immunomodulating, antimicrobial, antioxidant, anticancer, and antitumor properties. Molecular mass, branching configuration, conformation of polysaccharides and chemical modification are the major factors influencing their biological activities. The mechanism of action of mushroom polysaccharides is to stimulate T-cells, B-cells, natural killer cells, and macrophage dependent immune responses via binding to receptors like the toll-like receptor-2, dectin-1. The present review offers summarized and significant information about the structural and biological properties of mushroom polysaccharides, and their potential for development of therapeutic materials.
... Similarly, AbM isolated from A. brazei contains diverse polysaccharide-protein complexes with different chemical linkages such as β-1,6-glucan, α-1,6and α-1,4-glucan, glucomannan and β-1,3-glucan. AbM has been shown to have immunomodulatory and antineoplastic properties [28]. Polysaccharides and polysaccharide-protein complexes from other medicinal mushrooms that have shown immunomodulatory effects are listed in Table 2. Heteroglycan, Glycoprotein, Glucomannan-protein complex, β-1,3-d-glucan, with β-1,6-d-glucan branch Stimulates Natural Killer (NK) cells, macrophages, dendritic cells, and granulocytes; induction of Tumor Necrosis Factor (TNF), Interferon (IFN)-γ, and Interleukin (IL)-8 production [29] Auricularia auricula-judae AF1 β-1,3-d-glucan main chain with two β-1,6-d-glucosyl residues Induces apoptosis of cancer cell [30] Gymnopus dryophilus (syn. ...
... Similarly, AbM isolated from A. brazei contains diverse polysaccharide-protein complexes with different chemical linkages such as β-1,6-glucan, α-1,6and α-1,4-glucan, glucomannan and β-1,3-glucan. AbM has been shown to have immunomodulatory and antineoplastic properties [28]. Polysaccharides and polysaccharide-protein complexes from other medicinal mushrooms that have shown immunomodulatory effects are listed in Table 2. Heteroglycan, Glycoprotein, Glucomannan-protein complex, β-1,3-d-glucan, with β-1,6-d-glucan branch Stimulates Natural Killer (NK) cells, macrophages, dendritic cells, and granulocytes; induction of Tumor Necrosis Factor (TNF), Interferon (IFN)-γ, and Interleukin (IL)-8 production [29] Auricularia auricula-judae AF1 β-1,3-d-glucan main chain with two β-1,6-d-glucosyl residues Induces apoptosis of cancer cell [30] Gymnopus dryophilus (syn. ...
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Mushrooms have been valued as food and health supplements by humans for centuries. They are rich in dietary fiber, essential amino acids, minerals, and many bioactive compounds, especially those related to human immune system functions. Mushrooms contain diverse immunoregulatory compounds such as terpenes and terpenoids, lectins, fungal immunomodulatory proteins (FIPs) and polysaccharides. The distributions of these compounds differ among mushroom species and their potent immune modulation activities vary depending on their core structures and fraction composition chemical modifications. Here we review the current status of clinical studies on immunomodulatory activities of mushrooms and mushroom products. The potential mechanisms for their activities both in vitro and in vivo were summarized. We describe the approaches that have been used in the development and application of bioactive compounds extracted from mushrooms. These developments have led to the commercialization of a large number of mushroom products. Finally, we discuss the problems in pharmacological applications of mushrooms and mushroom products and highlight a few areas that should be improved before immunomodulatory compounds from mushrooms can be widely used as therapeutic agents.
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Since the 1980s, medicinal effects have been documented in scientific studies with the related Basidiomycota mushrooms Agaricus blazei Murill (AbM), Hericium erinaceus (HE) and Grifola frondosa (GF) from Brazilian and Eastern traditional medicine. Special focus has been on their antitumor effects, but the mushrooms’ anti-inflammatory and antiallergic properties have also been investigated. The antitumor mechanisms were either direct tumor attack, e.g., apoptosis and metastatic suppression, or indirect defense, e.g., inhibited tumor neovascularization and T helper cell (Th) 1 immune response. The anti-inflammatory mechanisms were a reduction in proinflammatory cytokines, oxidative stress and changed gut microbiota, and the antiallergic mechanism was amelioration of a skewed Th1/Th2 balance. Since a predominant Th2 milieu is also found in cancer, which quite often is caused by a local chronic inflammation, the three conditions—tumor, inflammation and allergy—seem to be linked. Further mechanisms for HE were increased nerve and beneficial gut microbiota growth, and oxidative stress regulation. The medicinal mushrooms AbM, HE and GF appear to be safe, and can, in fact, increase longevity in animal models, possibly due to reduced tumorigenesis and oxidation. This article reviews preclinical and clinical findings with these mushrooms and the mechanisms behind them.
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Polysaccharides are a structurally diverse group of biological macromolecules of well-known occurrence in nature. The mushroom, plant and other polysaccharides draw a lot of attention due to their several difficult biological properties, such as, anticancer, antiviral, immunomodulating, antimicrobial, anticoagulant, antidiabetic, antioxidant, and antitumor activities. Several bioactive glucans and heteroglycans were isolated from different mushroom, plant and bacterial cell wall. Polysaccharides have highest ability for carrying biological information comparison with other biopolymers such as proteins and nucleic acids due to the structural variability. It is the focus of this review to bring together the available knowledge of the structure, and function of the different polysaccharides of the mushroom, plant and bacterial cell wall.
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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.
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A mushroom extract, Agaricus blazei Murill Kyowa (ABMK), has been reported to possess antimutagenic and antitumor effects. Here, we investigate the beneficial effects of ABMK consumption on immunological status and qualities of life in cancer patients undergoing chemotherapy. One hundred cervical, ovarian, and endometrial cancer patients were treated either with carboplatin (300 mg/m ² ) plus VP16 (etoposide, 100 mg/m ² ) or with carboplatin (300 mg/m ² ) plus taxol (175 mg/m ² ) every 3 weeks for at least three cycles with or without oral consumption of ABMK. We observed that natural killer cell activity was significantly higher in ABMK-treated group (ANOVA, n = 39, P < 0.002) as compared with nontreated placebo group ( n = 61). However, no significant difference in lymphokine-activated killer and monocyte activities was observed in a manner similar to the count of specific immune cell populations between ABMK-treated and nontreated groups. However, chemotherapy-associated side effects such as appetite, alopecia, emotional stability, and general weakness were all improved by ABMK treatment. Taken together, this suggests that ABMK treatment might be beneficial for gynecological cancer patients undergoing chemotherapy.
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For many years, innate immunity has been considered as a separate entity from the adaptive immune response and has been regarded to be of secondary importance in the hierarchy of immune functions. For the past few years, however, interest in innate immunity has grown enormously, so that now it is studied intensively in many laboratories that seek to integrate these two distinct types of immune function. Our intent in this review is to point out the similarities and differences in these two types of host response to infection, and to indicate our present level of understanding of how these can be integrated into a more complete description of the immune response.
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Agaricus blazei is a medically important mushroom widely eaten and prescribed in Japan. Polysaccharide fractions were prepared from cultured A. blazei by repeated extraction with hot water (AgHWE), cold NaOH (AgCA), and then hot NaOH (AgHA). By chemical, enzymic, and NMR analyses, the primary structures of AgHWE, AgCA, and AgHA were mainly composed of 1,6-β-glucan. Among these fractions, the NaOH extracts showed antitumor activity against the solid form of Sarcoma 180 in ICR mice. To demonstrate the active component in these fractions, several chemical and enzymic treatments were applied. These fractions were found to be i) neutral β-glucan passing DEAE-Sephadex A-25, ii) resistant to periodate oxidation (I/B) and subsequent partial acid hydrolysis (I/B/H), iii) resistant to a 1,3-β-glucanase, zymolyase, before I/B, but sensitive after I/B/H. In addition, after I/B/H treatment of the neutral fraction of AgCAE, a signal around 86 ppm attributable to 1,3-β-glucosidic linkage was detectable in the 13C-NMR spectrum. These facts strongly suggest that a highly branched 1,3-β-glucan segment forms the active center of the antitumor activity.
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There is scientific evidence to suggest that the medicinal mushroom Agaricus blazei Murrill (AbM) has immunomodulatory effects on cytokine synthesis, both in vitro and in vivo. This study was the first randomized, double-blind, placebo-controlled trial designed to investigate these purported actions in elderly women. The objective of this study was to ascertain the effects of AbM intake on serum levels of interleukin-6 (IL-6), interferon-gamma (IFN-γ) and tumour necrosis factor-alpha (TNF-α) in community-living seniors. The sample consisted of 57 elderly females who were carriers or homozygous for the majority allele of functional polymorphisms for the chosen cytokines. Subjects were randomly allocated to receive placebo (n = 29) or AbM dry extract (n = 28), 900 mg/day for 60 days. Body mass index, abdominal girth, body composition, blood pressure and cytokine (IL-6, IFN-γ, and TNF-α) levels were measured, and food intake was assessed as a possible confounder. Analysis of these parameters showed the sample was characterized by overweight and excess adiposity. After the study period, no changes from baseline were detectable for any parameter in either group. In this study, AbM extract had no modulating effect on IL-6, IFN-γ or TNF-α levels in elderly females.
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Ipomoea batatas, Agaricus blazei and Smallanthus sonchifolius are known to favorably influence diabetes mellitus. To clarify their antidiabetic efficacy and hypoglycemic mechanisms, we treated streptozotocin-induced diabetic rats with daily oral feeding of powdered Ipomoea batatas (5 g kg(-1) d(-1)), Agaricus blazei (1 g kg(-1) d(-1)) or Smallanthus sonchifolius (4 g kg(-1) d(-1)) for 2 months. Treatments with Ipomoea batatas or Agaricus blazei, but not Smallanthus sonchifolius, significantly suppressed the increases of fasting plasma glucose and hemoglobin A1c levels, and restored body weight loss during diabetes. Serum insulin levels after oral glucose administration tests increased along the treatments of Ipomoea batatas or Agaricus blazei. Moreover, Ipomoea batatas and Agaricus blazei reduced superoxide production from leukocytes and vascular homogenates, serum 8-oxo-2'-deoxyguanosine, and vascular nitrotyrosine formation of diabetic rats to comparable levels of normal control animals. Stress- and inflammation-related p38 mitogen-activated protein kinase activity and tumor necrosis factor-α production of diabetic rats were significantly depressed by Ipomoea batatas administration. Histological examination also exhibited improvement of pancreatic β-cells mass after treatments with Ipomoea batatas or Agaricus blazei. These results suggest that hypoglycemic effects of Ipomoea batatas or Agaricus blazei result from their suppression of oxidative stress and proinflammatory cytokine production followed by improvement of pancreatic β-cells mass.
Multiple myelomas are a less frequent cancer site among both sexes. On a worldwide scale, it is estimated that about 86 000 incident cases occur annually, accounting for about 0.8% of all new cancer cases. About 63 000 subjects are reported to die from the disease each year, accounting for 0.9% of all cancer deaths. Geographically, the frequency is very unevenly distributed in the world with the highest incidence in the industrialised regions of Australia / New Zealand, Europe and North America. Incidence and mortality seem to be stable in Asian countries and to increase slowly over the decades among whites in the western countries. The etiology is poorly understood. This depends partly upon the fact that the risk factors which play a major role for malignant diseases in general, such as tobacco consumption and diet have not been found strongly involved into multiple myeloma etiology. Nevertheless, some consistency seems to be in the findings about a risk elevation with obesity and a slightly decreased risk with high fruit consumption. Despite some contradicting results, indications to a role of ionising radiation persist. Finally, infections with HIV and hepatitis C virus appear related to an elevated multiple myeloma risk. Currently, large efforts are undertaken to unravel the etiology of malignant lymphoma including those of multiple myeloma.