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4.Cancer prevention effects observed through
animal experiments
Cancer proliferation inhibition effect of Agaricus
Blazei Murrill is confirmed through experiments with mice. Administration of
antioncogenous polysaccharide originated from Agaricus Blazei Murrill to the
subject mice was started from 10 days before cancer transplanting. Then
"Sarcoma 180" solid cancer was transplanted to subcutis of the mice 24 hours
after the final administration. After the transplantation, polysaccharide was
not administered to the mice. Physiological salt solution was administered and
the same cancer was transplanted to another group of mice for comparison.
Anticancer effect was judged by comparison of tumor inhibition, complete
disappearance and survival rates. From the result shown in Table 3, complete
disappearance was observed in 5 cases out of 10 for the group of mice that
received 10mg/kg and in 7 cases out of 10 for the group which received 20mg/kg.
Tumor impediment rate was 64.1%, 79.6% and 94.2% for the group that received
5mg/kg, 10mg/kg and 20mg/kg respectively. Thus, anticancer effect was confirmed
and it is dependent on the amount of polysaccharide.
5. Agaricus Blazei Murrill is also effective
against cancer induced by chemical carcinogen
It is said that more than 80% of human cancer is
caused by chemical substances in the environment. Neutral polysaccharides
(b-D-glycan, xyloglycan), acid hetero-polysaccharide (uronyde, a kind of
galactoglycan), proteinic polysaccharide (peptide glycan) and nucleic acid
elements (ribonucleotide protein) are the components of Agaricus Blazei Murrill
enabling anticancer activity.
Fibroblastemic sarcoma (cancer) induced by chemical
carcinogen called methylcholanthrene was transplanted to subcutis of mice.
FIII-2-b originated from Agaricus Blazei Murrill (complex of b-D-glycan and
protein), 5-FU (fluorouracil) and ATOM (mycelium polysaccharide obtained from
Agaricus Blazei Murrill) were administered to the mice from 24 hours after the
transplantation in order to examine the anticancer effect.
From the result shown in Figure 2, it is observed that
FIII-2-b and 5-FU inhibits the proliferation of cancer independently. It is
also confirmed that 5-FU, when administered together, remarkably increased the
anticancer effect of polysaccharide extracted from Agaricus Blazei Murrill.
Cell-destroying anticancer medicine also affects normal cells. Strong side
effects are expected especially in hematopoietic, bone marrow and digestive
systems. However, it is possible to reduce the dosage and side effects by using
Agaricus Blazei Murrill concomitantly. It also enables long term administration
of anticancer medicine to increase the effect of treatment.
It was confirmed from the result of Table 4 that a
mycelium polysaccharide of Agaricus Blazei Murrill also shows anticancer
activity against fibroblastemic sarcoma.
6. Agaricus Blazei Murrill is effective against
naturally generated adenocarcinoma of mammary gland of mice
The tumor called "Shionogi 42" is the adenocarcinoma
that naturally generated in the mammary gland at the left groin of female mice
of "dds (DS) family" that were raised in Aburabi Farm at Shionogi Co., Ltd.
Research Center in 1959. This cancer is transplantable to DS mice of family
only and as shown in Table 6, it is difficult to cure this cancer with
conventional anticancer medicine.
The tumor inhibition rate 25.1% as the result of ATOM
administration at 100mg/kg dosage is not so convincing, but at 300mg/kg dosage,
the inhibition rate rose to 48.5%. It was also observed that polysaccharide
originated from Agaricus Blazei Murrill shows stronger cancer inhibition
activity than anticancer medicines such as mitomycin C (antioncogenous
antibiotic) or fluorouracil (pyrimidine metabolism antagonizing antitumor
medicine).
7. Steroid content of Agaricus Blazei Murrill
inhibits proliferation of uterocervical cancer cell that originated in human
body
Agaricus Blazei Murrill's inhibition system inhibits,
destroys and stops proliferation or metastasis of carcinoma cell by activating
and reinforcing the self-defense system naturally endowed to the host, i.e.
immunity function. This function can be divided into specific and non-specific
immunity. Typically, immunity function is exercised by lymphocyte (T- and
B-lymphocyte) that exists in the blood, antibody (globulin), complement,
macrophage (a serum protein enzyme that plays an important role in
bacteriolysis, phagocytosis and immune cytolysis, activated by various
antigen-antibody reaction), leukocyte, etc. In addition to various
polysaccharides which shows anticancer activity by strengthening the immunity
function, Agaricus Blazei Murrill contains steroids that directly affect
carcinoma cells and inhibit cancer proliferation in the manner similar to that
of typical chemotherapeutic medicines. Three out of six kinds of steroids
dissociated from the acetone extract of Agaricus Blazei Murrill were found to
have inhibition effect against the proliferation of carcinoma cell in a test
tube.
It is reported that the steroids with structures shown
as formula 1,2 and 4 of Figure 3 inhibited the proliferation of carcinoma cells
at such low density as 8ppm, 16ppm and 64ppm respectively, in an experiment
using HeLa cells (uterocervical cancer cell that originated in human body).
Ergosterol, a precursor of vitamin D, does not show an
anticancer action by itself. However, it has been made clear that the new
synthetic steroid biosynthesized from ergosterol (structural formula 3 of in
Figure 3) also works as an inhibitor against proliferation of carcinoma cells.
Even if carcinoma cells are generated in the body, it does not immediately
start carcinogenesis. Considering the fact that it takes years for carcinoma
cells to proliferate and undermine the body and finally cause carcinogenesis,
it can be said that Agaricus Blazei Murrill is a mushroom of wonder that
prevents every disease with its steroids content, directly inhibiting the
proliferation of carcinoma cells.
8. Concomitant use of Agaricus Blazei Murrill
and anticancer medicine results in synergistic effect
Krestin (PS-K) extracted from trametes versicolor, a
mushroom of polyporaceae family and letinan made of polysaccharide extracted
from lentinula edodes are clinically used as medicines for immunotherapy. These
medicines are said to be more effective when used with other anticancer
(chemotherapeutic) medicines. Concomitant use of polysaccharide extracted from
the mycelium of Agaricus Blazei Murrill (ATOM) and other anticancer medicines
was examined using Sarcoma 180 solid cancer. Starting from 24 hours after
transplantation of the cancer, ATOM was administered to the mice in the abdomen
for 10 consecutive days and other anticancer medicines were administered by
injection 3 times a week, for 2 weeks. As shown in Table 5, through concomitant
use with ATOM, it resulted in 4.8 times for mitomycin, 6.8 times for endoxan,
2.1 times for cytosine arabinosid and 6.3 times for fluorouracil synergistic
effect compared to single use of respective anticancer medicine. The data
suggests that the immunity activation effect of polysaccharide from Agaricus
Blazei Murrill increases the anticancer activity of other medicines and more
effective extermination of cancer can be expected by impeding the proliferation
of carcinoma cell through concomitant use.
9. Agaricus Blazei Murrill enhances the cancer
treatment effect of radiotherapy
Radiotherapy is a popular cancer treatment method, but
it also has a disadvantage of attacking normal cells as well as carcinoma
cells. NFT (Nakahara-Fukuoka Tumor) is a fiber sarcoma that naturally generated
in the subcutis of mice. This sarcoma was named after the doctors Kazuro
Nakahara and Fumiko Fukuoka at National Cancer Center of Japan who discovered
it in 1949.
Administration of ATOM does not produce anticancer
effect against this tumor. When it is administered twice with a week's interval
to NFT cells that received X-ray irradiation of 1500R, the mortality of mice
drops, but the tumor does not disappear completely. However, it was confirmed
that through concomitant use of Agaricus Blazei Murrill polysaccharide (ATOM)
and radiotherapy, the tumor in 40 - 50% of the mouse disappears completely. As
to Shionogi 42 cancer, when AST cells were administered of ATOM twice with a
week's interval after receiving X-ray irradiation of 1500R (this amount was
found to be appropriate through preliminary experiments), complete
disappearance rate increased and mortality remarkably dropped. Thus,
synergistic anticancer effect through concomitant use of Agaricus Blazei
Murrill and radiotherapy was confirmed in animal experiments. This mushroom
plays an important clinical role when used with radiotherapy as well as
anticancer medicines. Furthermore, the synergistic effect of ATOM and
radiotherapy was found to be more effective to female mice than male mice, as
shown in Table 6. Considering the similarity between mice and human being in
the aspects of life span difference between men and women, the data is very
interesting because it may be suggested that the same is true for human being.
10. The first step of treatment by anticancer
medicine is to understand its side effect.
Curing cancer is an earnest wish of mankind. Unlike
foreign microorganism, carcinoma cells are part of human body system and have
few differences from normal cells. This is the reason why anticancer medicine
cannot fully control the disease. In other words, there is yet no anticancer
medicine effective specifically against carcinoma cells. In some cases,
unfortunately, patients die sooner from lethal complication caused by the side
effect, even though the number of carcinoma cells may be reduced by the
treatment using anticancer medicine. Side effect is a big obstacle in the use
of anticancer medicines. There is no medicine without side effect and medicines
with fewer side effects are less effective against cancer. So, it is important
to understand the side effect as the first step of treatment by anticancer
medicines.
Many anticancer medicines clinically used today make a
covalent or non-covalent bond with DNA and affect the replication,
transcription and translation of DNA. Ironically enough, such medicine itself
is sometimes carcinogenic. It is commonly known that many of nitrogen mustard
derivatives used as alkylating medicines increase pulmonary and thymus tumor of
mice. It is also known that cyclophosphamide and endoxan increase mammary gland
tumor and mitomycin C used as antitumor antibiotic increases subcutaneous
sarcoma of mice. As such, an anticancer medicine ultimately has a possibility
to affect human body as a carcinogenic agent. Patients should be aware that it
is possible that an anticancer medicine used to cure the primary cancer may
cause the secondary cancer.
11. Agaricus Blazei Murrill helps recovery from the
inhibition of reticuloendothelial system function caused by anticancer
medicines
Popular clinical anticancer medicines such as
mitomycin C (MMC), fluorouracil (5-FU) and cyclophosphamide (CY) are known to
more or less inhibit the reticuloendothelial system function. In a study made
under the condition of Ehrlich ascites and gallbladder cancer, whereas K-value
of the subject group is 100, the K-value was significantly inhibited to 57% for
group administered with 1mg/kg of MMC, 60% for 20mg/kg of CY and 72% for
30mg/kg of 5-FU (see Figure 4).
At the same time, ATOM was found to prevent the said
inhibition of the reticuloendothelial system function caused by anticancer
medicine administration. Thus, the concomitant use of ATOM and anticancer
medicine reduces the side effect caused by the anticancer medicine and improves
the treatment effect.
12. Agaricus Blazei Murrill stimulates the
immunocompetent cells, improves the immunity function and stops the activity of
cancer
Figure 5 is the result of study made under gallbladder
cancer condition with weak immunity function to see whether Agaricus Blazei
Murrill shows an action to help the recovery of the immunity function. When the
polysaccharide extracted from Agaricus Blazei Murrill was administered, the
level of Thy1 and 2 positive cells (marker of all T-cells), L3T4 positive cells
(marker of helper/inducer T-cells) and Asisalo GM1 positive cells (marker for
natural killer cells and activated macrophage) significantly increased. From
this result, it can be observed that Agaricus Blazei Murrill prevents carcinoma
cell activities by strengthening the helper T-cells (commanders of immunity
system) and cooperating with macrophage and natural killer cells (guards and
soldiers).
13. Agaricus Blazei Murrill is also effective
against ascites cancer
Polysaccharides extracted from mushrooms of
polyporaceae family are generally effective against sarcoma 180 solid cancer.
But it is said that this effect cannot be expected against ascites cancer where
the growth of cancer is slow (they are scattered and floating under the
peritoneum) such as Ehrlich ascites cancer.
When ascites cancer is transplanted, all subjects die
from it within 2 weeks. Animals are considered to die from fast growth of
ascites cancer cells while the polysaccharides cannot improve the cancer
inhibition function of immune system in time. However, there are data (Table 7)
to show the effectiveness of Agaricus Blazei Murrill in animal experiments with
ascites cancer, for which the same effect could not be expected by using
traditional immunoactivating medicines.
14. Agaricus Blazei Murrill's lipid section is also
anticancer active
In addition to Agaricus Blazei Murrill's various
polysaccharide section, its lipid section was also found to have anticancer
effect. As shown in Figure 6, a group of mice (10 subjects) transplanted of
ascites cancer survived only 15.0 days as an average. But another group
administered with 150mg/kg of lipid section of Agaricus Blazei Murrill survived
19.7 days and with 300mg/kg survived 30.6 days as an average. The cancer on 2
subjects out of 10 had completely disappeared. Thus, the lipid section was
confirmed to be anticancer active against Ehrlich ascites cancer.
15. Agaricus Blazei Murrill activates macrophage
Agaricus Blazei Murrill contains 3.6 % of lipid, of
which 26.8% is neutral lipid and 73.2% is phospholipid. So phospholipid is the
primary part of the mushroom's lipid. The lipid can be decomposed into linolic,
palmitic, oleic and palmitoleic acids, each of which is observed to be
anticancer active against ascites cancer. Macrophage was also found activated
in the group of mice administered with the lipid section of Agaricus Blazei
Murrill. It is known that such activated macrophage plays an important role in
biophylaxis in addition to anticancer activity.
16. Agaricus Blazei Murrill proved to be more
effective against ascites cancer than other anticancer medicines
Antioncogenous polysaccharides obtained from other
mushrooms are generally considered to be effective only against solid cancer.
However, as already explained, polysaccharides obtained from Agaricus Blazei
Murrill is effective against ascites cancer as well as solid cancer. Table 8 is
the result of comparison between the anticancer effects of Agaricus Blazei
Murrill polysaccharide (ATOM) and other anticancer medicines against Ehrlich
ascites cancer transplanted to mice. ATOM and other anticancer medicines were
administered in the amount shown in Table 8 for 10 consecutive days, starting
from 24 hours after the transplantation. Comparing the number of survival days
of each group of mice, the group administered with 100mg/kg of ATOM survived
168.5% longer than the control group. Furthermore, the longevity rate
remarkably increased to 237% by concomitantly using MFC (administration of 1/3
of appropriate dosage of mitomycin C, fluorouracil and cytosine arabinosid). It
was also confirmed that ATOM by itself at 50mg/kg and 100mg/kg dosages was more
effective in anticancer activity than fluorouracil or cytosine arabinosid.
Thus, ATOM extracted from Agaricus Blazei Murrill is more effective against
ascites cancer than other anticancer medicines for clinical use.
17. Agaricus Blazei Murrill activates
reticuloendothelial system function
Reticular cells in liver, spleen, lymphoid tissues and
bone marrow and macrophage neutrophils in lungs and under peritoneum are
typically involved in reticuloendothelial system activity. In the experiment of
administering 150mg/kg and 300mg/kg of Agaricus Blazei Murrill polysaccharide
(ATOM) for 10 consecutive days from 24 hours after transplantation of Ehrlich
ascites cancer, the phagocytosis index K (the unit of reticuloendothelial
system activity indicating its capacity to catch and eat large particles such
as bacterium, protozoa, perished tissue cell and colloid particle. Carbon
clearance values were examined as its guideline in this experiment) rose
significantly in comparison with the control group (see Figure 7).
This result is at the same level as the one obtained
by administration of 10KE/kg of picibanil (an immunopotentiative anticancer
medicine obtained from streptobacteria of group A, type 3) or 100mg/kg of PSK
(an immunopotentiative anticancer medicine obtained from mycelium of trametes
versicolor).
The organ weight of liver, spleen and thymus increased
significantly in comparison with the control group, by orally administering
ATOM under Ehrlich ascites cancer as shown in Figure 8. Since liver and spleen
create single-nucleus cells including macrophage and thymus involved in the
immunity activity, such increase in their weight it suggests that concomitant
use of ATOM with anticancer medicines is effective from the aspect of side
effect reduction in cancer treatment.
18. Agaricus Blazei Murrill can be a solution to
allergic diseases without fear of side effects
When foreign substance (antigen) such as virus, drug,
pollen or indoor dust enters human body, the human body distinguishes the
substance and makes a weapon (antibody) to attack and expel such substance.
This is called immunoreaction. Symptom of allergy such as asthma and atopy
breaks out in the same manner as immunoreaction. Normally, immunoreaction
occurs in order to protect the body from germs. However, in the case of a
person with allergy, the reaction lacks normal control and it does harm to the
body. The cause of allergy is an antibody called IgE (immunoglobulin E) created
by B-cells which are involved in immunity system. Substance which triggers
allergic reactions such as cedar pollen or mite are called allergen. When the
body is repeatedly exposed to allergen, the antibody IgE will be created. And
the antibody IgE attached to mast cells discharges substances including
histamine, causing organic reactions including an itchy feeling. Symptoms such
as atopic dermatitis, allergic rhinitis and bronchial asthma are caused by
histamine.
Therefore, antihistaminic that controls the isolation
of histamine from mast cells is used for treatment of allergy as well as
steroid. But traditional antihistaminic very frequently causes sleepiness as a
side effect. We have so far learned that Agaricus Blazei Murrill, as its
anticancer action, is closely involved in the functions of macrophage and
complement supporting the immunity system, activation of reticuloendothelial
system and T-lymphocyte functions. So we examined the antiallergy effect of
ABWE (hot water extract of Agaricus Blazei Murrill). The experiment result is
shown in Tables 9 and 10, and in Figure 9. See Table 9 first. This is the
result of inhibition of histamine isolation from peritoneal mast cells of
unsensitized rats that was induced by compound 48/80 (histamine isolator).
Administration of 200mg/ml, 500mg/ml and 1000mg/ml of ABWE resulted in
isolation rate of 77.2±5.7%, 67.4±5.7% and 49.1±5.0% and
inhibition rate of 11.9%, 23.1% and 44.0% respectively.
Table 10 shows the isolation of histamine from cells
sensitized by antiserum involving antibody IgE. The isolation rate after
administration of 200mg/ml, 500mg/ml and 1000mg/ml of ABWE was
28.9±3.0%, 24.6±2.1% and 20.1±2.3% and inhibition rate was
3.9%, 19.1% and 33.9% respectively. The inhibition rates with 500mg/ml and
1000mg/ml are significant. Figure 9 shows the inhibition of histamine
contraction of a guinea pig intestine piece. Immediately after 1ml of 120,000x
histamine solution was infused, a strong intestinal contraction started as
shown in the figure. While the contraction continued, 1ml of 1,200,000x
solution of diphenhydramin was infused. Then a strong inhibition action was
immediately observed. A similar experiment was made with 1ml of 10x ABWE
solution using another piece of intestine. The inhibition action was observed
after a latent period of about 2 minutes (see the middle line of the figure).
This inhibition action was also observed with 1ml of 50x ABWE solution (see the
bottom line of the figure).
Unlike other medicines, an edible mushroom Agaricus
Blazei Murrill will not cause any side effect.
19. Clinical data confirms that Agaricus Blazei
Murrill improves hepatic function
From the data obtained through my joint research with
Dr. Wang Jun Zhi of Lanzhou Medical Institute of China, daily administration of
20mg of Agaricus Blazei Murrill brought about various effects including hepatic
function improvement and negative index of virus activity in chronic hepatitis
B patient (see Table 11).
Dr. Wang divided 20 patients into an experimental
group and a control group. Each member of the experimental group took Agaricus
Blazei Murrill and the control group received ordinary treatment only. The
result was compared 3 months later and it was confirmed that the treatment
effect on the experimental group was 2 significant, 8 effective and 0
ineffective, while the effect on control group was 1 significant, 6 effective
and 3 ineffective. The difference in hepatic function improvement is especially
noteworthy. GOT, GPT, connective bile acid, serum iron protein, total bilirubin
and prothrombin values of the experimental group also indicated the mushroom's
remarkable effectiveness in keeping hepatic function in order. These clinical
data proves that Agaricus Blazei Murrill promotes the recovery of the hepatic
cell of a chronic hepatitis patient. And the effect will be retained after
treatment.
20. Agaricus Blazei Murrill's immunopotentiation
effect strongly supports pancreas
Let me explain about Agaricus Blazei Murrill's effect
against diabetes, a life custom disease that causes various complications.
Diabetes is caused by insufficiency of insulin, a hormone that is secreted from
pancreas. Insulin helps human body utilize glucose as a source of energy. When
there is an insufficiency of insulin, human body cells cannot absorb the energy
and the sugar will be left in the blood. Under this condition, human body
becomes easily tired and its resistance against foreign enemy becomes weak. As
a result, infectious diseases and various disabilities may be caused.
Therefore, in order to control the blood sugar value, medical treatment is very
important as well as dietary control and physical exercise. Insulin will be
administered for diabetes. However, any effective medicine carries a risk of
side effect, depending on the usage. In the case of insulin, it may cause
hypoglycemia as a side effect. Considering the possibility of a treatment that
is safe and independent on medicines, Agaricus Blazei Murrill would play a
really big role with its immunopotentiation effect.
Agaricus Blazei Murrill research group has confirmed
the effect in the experiment of mice with diabetes. The disability of the
Langerhans' islands of their pancreas caused the diabetes. Agaricus Blazei
Murrill successfully activated the immunity system of these mice and inhibited
the progress of diabetes (see Chart 1).
21. Agaricus Blazei Murrill contributes to the
prevention of diabetes-related complications
It is regrettable that it is still impossible to cure
diabetes completely, even with the advanced medicine of today. However,
neglecting the disease may lead to various complications and it is sometimes
fatal. Therefore, treatment of diabetes is focused on control of blood sugar
level and prevention of complications. Vegetable fiber is said to be effective
in preventing the increase of blood sugar level. Vegetable fiber means
everything that cannot be digested with human digestive enzyme, such as
indigestible high polymer polysaccharides, cellulose, pectic substance, chitin
and chitosan.
It is important to take vegetable fiber as a treatment
of diabetes because (1) vegetable fiber contains low energy, (2) it is not
insulin-stimulant and (3) it causes inhibition and delay in absorption of
nutrient, so that it slows down the rise of blood sugar level.
Agaricus Blazei Murrill contains abundant vegetable
fiber such as b-D-glycan, heteropolysaccharides (pectic substance,
hemicellulose) and chitin. In order to avoid complications, it is also
important to prevent arteriosclerosis as well as keeping normal blood sugar
level. Agaricus Blazei Murrill also contains linolic acid. Linolic acid has a
similar function as vegetable fiber to reduce blood cholesterol (see Figure
10).
Agaricus Blazei Murrill is also a food of high
nutritive value, since it contains various amino acids, vitamin B and D,
magnesium, potassium, etc. Diabetes patients tend to become sensitive about
calorie value and take low energy meals with insufficient vitamin and mineral.
Agaricus Blazei Murrill contains abundant vitamin and mineral and will provide
desirable supplementary nutrition.
Treatment of diabetes takes a long time. Instead of
using medicines with a threat of side effects, patients can take Agaricus
Blazei Murrill without any fear. This is an important option for diabetes
patient.
22. Many effective components included in Agaricus
Blazei Murrill repair and maintain homeostasis
Due to the problematic medical practice of "soaking"
patients with medicine and patients' anxiety related to it are urging patients
to look at oriental medicine. Anyway, what do we expect from oriental medicine?
One of the things we expect must be its attitude towards diseases. In oriental
medicine, every disease is caused by the disorder of homeostasis of body. A
disease is a local result from loss of balances between false/true, cold/hot,
positive/negative and spirit/blood. Therefore, oriental medicine focuses on
repairing homeostasis and increasing immunity. With such a philosophy, oriental
medicine is useful in treating physical weakness during the recovery period
from a disease and chronic or ill-defined diseases such as fatigue, cold
constitution, lumbago, climacteric disorders and anxiety. While repairing
homeostasis, Chinese herbs are also considered to be effective against chronic
hepatitis, chronic rheumarthritis and bronchial asthma, which cannot be cured
by western medicine. Numerous well-balanced components of Agaricus Blazei
Murrill will correct the lost balances, ease various strains and maintain
homeostasis. The b-D-glycan is also contained in the mushroom for improvement
of immunity function. The edible mushroom Agaricus Blazei Murrill's effect in
improving both homeostasis and immunity will also be well supported from the
viewpoint of oriental medicine.
Table 1
The effect of polysaccharides extracted
from basidiomycetes and bacteria against "Sarcoma 180" solid cancer |
