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More than 50 edible mushrooms, considered food in Asian countries, have therapeutic effects. Although all of them do not have any toxicity and are well tolerated, only six have been amply investigated. Among them, the mushroom Maitake distinguished itself for its immune-stimulating activity of antineoplasic and antiviral use; it reduces cholesterol, triglycerides and high glucose levels in patients who suffer diabetes, adult type, and contributes to controlling arterial tension. Its excellent tolerability, proven benefits and its compatibility with other treatments of synthetic drugs make this mushroom an extraordinary complement for treatments against various conditions and chronical sicknesses. |
Press the bottle to see a photo of this plant |
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Introduction
In Japan , during more than 3,000 years, people have benefited by this giant mushroom, but only in 1980 its therapeutic properties have been identified. In that country, it is very much appreciated for its culinary qualities as well as for its therapeutic properties.
Its scientific denomination is Grifola Frondosa which comes from Gryphon, a Greek mythological beast with head and wings of an eagle and a lion's body and leafy (frondosa) for its leaves. In Japanese, "mai" means "dance" and "take" means mushroom, which together is "dancing mushroom". Apparently, this name comes from the form of its fruits that stand out and move in the wind.
In feudal times, Maitake was considered so valuable that its weight was paid for in silver. Even at present, the mushroom collectors keep the knowledge of the sites where it grows to themselves. Maitake is appreciated by the chefs for its excellent taste and texture and by other people for its therapeutic usefulness.
Maitake grows in large quantities at the foot of various trees. It achieves its optimum growth within a limited range of temperatures, humidity and other environmental factors. Some areas in the North East of Japan are particularly appropriate for its growth in the wilds. Maitake can also be found in the Northern forests of Asia, Europe and in the East of the United States . Although it is relatively rare in Japan , it is not strange to find it in the forests of the U. S. A. and Canada where it is known as "the forest hen" due to its form and color that resemble the feathers of that bird. It is very seldom only in the Western forests of the United States .
Maitake farming is rather recent only. During the last decades, the change from wild Maitake into mushroom farming has been achieved. Commercial growing in Japan was initiated in 1981 with 325 tons. In 2001 the commercial Maitake production worldwide exceeded 40,000 ton per year. |
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Active Components:
Various active components with proven antineoplasic and immune-modulating activities have been isolated from 30 species of mushrooms. Only some of them have passed the following phase: clinical objective evaluation of its antineoplasic and immune-modulating potential in humans. Many of its active mycotic components are chemically related with the structure ß -D-glucan (which means polymers of d-glucose with some other monosaccharides) or ß -D-glucose linked to proteins (the so-called peptids-polysaccharids or proteoglycanes). In general, the proteoglycanes offer a higher immune-stimulating activity that the one that corresponds to the free glucanes.
At the beginning of the decade of the 80s, the Japanese mycologist Hiroaki Nanba of the Pharmaceutical University of Kobe cam to the conclusion that the polysaccharides of Maitake had a unique structure and showed in animal tests that its consumption achieved a significant anti-tumor and immune-modulating effect, superior to the one of other medicinal mushrooms. Nanba decided to concentrate exclusively on Maitake and, together with some other Japanese scientists, began the extraction of various polysaccharides to prove their immune-modulating and neoplasic potential.
In 1984, Nanba identified in the mycelium and in the fruit of Maitake a fraction with the capacity to stimulate the macrophages. This fraction was obtained from Maitake treating the fruit of the mushroom with hot water and saturating the resulting watersoluble extracts with 80% ethylalcohol. The precipitate is later treated with acetic acid and an alkaline material. The resulting fraction, called D-fraction, is a standardized form of polysaccharide compounds beta-1,6 and beta-1,3 glucane and a protein with a molecular weight close to 1,000,000.
That year, professor Nanba obtained the patent on this active component. Despite other medicinal mushrooms having proved to contain bioactive beta-glucanes, Nanba states that there are variations between the different beta-glucanes and that the beta-glucanes of the D-fraction of Maitake have a unique and complex structure, containing both: a principal chain 1,6 with a higher grade of ramifications 1,3 and a principal chain 1,3 with ramifications 1,6.
The basic ß -D-glucane is a repetitive structure of D-glucose united in lineal chains by beta (ß ) links. These may extend from the carbon 1 of a saccharide ring to carbon 3 of the next ( ß ); from carbon 1 to carbon 4 ( ß 1 - 4 ) or from carbon 1 to carbon 6 ( ß 1 - 6 ). Frequently, there is a principal chain ß 1 - 3, ß 1 - 4 or ß 1 - 3, ß 1 - 4 mixed with lateral chains ß 1 - 6. The basic repetitive structure of ß 1 - 3 glucane with lateral chains ß 1 - 6 can be appreciated in figures 1 and 2.
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The hetero- ß -D-glucanes, lineal polymers of glucose with other D-monosaccharides, have an antineoplasic and immune-modulating activity, but the alpha-D-glucanes usually lack these properties.
Ten active components of medicinal mushrooms have shown some significant clinical efficiency in the treatment of human neoplasias and AIDS, among them: D-fraction , MD -fraction, grypholane, the glucanes and proteoglucanes of Maitake. |
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The beta 1,6 glucane is recognized as the most effective agent to stimulate the cellular immunological replies. This substance increases the activity of the macrophages and other immune-competent cells that destroy tumor cells, like the lymphocytes NK (natural killers), lymphocytes T cytoxic (Tc) from 1,5 to 3 times, and the lymphocytes T helpers CD4+ (T-helper), the cells affected by HIV. Maitake also improves the immunological efficiency of these cells, increasing the production of cytotoxic substances by the macrophages, of interleukina-1, interleukina-2 and lymphokinas that activate the lymphocytes T and of superoxide-anions that eliminate tumor cells. The final result is an increase of the defenses against infectious diseases, |
Most of the beta-glucanes, derivates from medicinal mushrooms, have a principal chain 1,3 with ramifications 1,6 only. Other fractions, also derivates of Maitake, like the fraction-X are beta 1-6 glucane with ramifications alpha-1,4. It is thought that the higher the grade of ramifications, the more probable is the activation of a major number of immune-competent cells.
The high molecular weight of fraction-D is one of the factors which explains its immune-modulating effects, according to the studies on the anti-tumor activity and the glucose consumption of the macrophages. The relation between ramification and molecular weight of the beta-1,3 glucanes is also an important factor for the production of cytokines by the macrophages.
The anti-tumor mechanisms of the various species of medicinal mushrooms, including Maitake, are mediated by lymphocytes T and macrophages. Despite the structural and functional similarities between the various mycotic beta-glucanes, these differ in their efficiency against specific tumors and their capacity to elicit various cellular replies, particularly the production and expression of cytokines.
In the decade of the 90s, professor Nanba and his collaborator Keiko Kubo achieved a major purification of fraction-D which lead to the isolation of a more potent component, fraction-MD, on which they received a North American patent. This fraction is a hygroscopic powder, neutral or slightly acid, with a molecular weight close to 1,000,000.
Fraction-MD is extracted and fractioned from the myceliums and the fruits of Leafy Gryphole or G. albicans, G. umbellate or G. gigantea. The process is similar to the one described in the Japanese patent for fraction-D; however, Nanba and Kubo added an additional key step to the process of fraction-D, which removes the floatings by adding alcohol, which leads to a final concentration of 20 to 60 volume percent of water-soluble grifola extract.
The analyses show that, similar to fraction-D, the principal component of fraction-MD is a glucane/protein complex in the range from 80:20 to 99:1.10. Essentially, the fractions D and MD contain the same configuration of beta-glucane chains, but fraction MD is more purified and offers significantly higher results of antineoplasic studies, inhibiting tumor growth, and stimulating the immune replies dependent on macrophages and lymphocytes T killers.
Fraction D as well as fraction MD are considered safe and free of toxicity. |
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Mechanism of Action:
The bioactive glucanes and proteoglucanes isolated from medicinal mushrooms are the most promising class of immunoceutics. Without any doubt, they are able to increase all the mediators of immune replies. After decades of experiments with these substances, much of their mechanism of action is known but the site where they act, seems to be the dendritic cells or Langerhans cells.
The dendritic cells, of which the Langerhans cells are the ones resident in the skin and mucous membranes, are able to detect the threat from exogenous or endogenous substances and to mobilize the appropriate immune replies.
Given their wide localization in the tissues, the dendritic cells constitute the first line of defense of the immune intelligence. They are also the first cells to have contact with administered glucanes. When the glucanes enter the oral cavity, they are detected by the Langerhans cells of the oral mucous membranes and later by the dendritic cells of the stomach and intestines. After having been absorbed and circulated to the liver, the Kupffer cells (a type of dendritic cells) can detect these substances. The glucanes reaching the lymphatic ganglions are phagocyted by the dendritic cells of these ganglions. Some molecules of proteoglucanes are absorbed and intactly reach the circulating current where they stimulate the phagocytic activity of the leukocytes.
The capitation of glucanes and proteoglucanes activates the dendritic cells, acting as antigenical stimulus. The proximity of these substances to the cellular membrane of the lymphocytes T (NK) results in their activation and in an increase of their actions. The increase of cytotoxic activity of these lymphocytes is related with a favorable post-operational evolution in patients with gastritic cancer. The infiltration of glucanes and proteoglucanes in a human gastric tumor before the surgical resection has activated the lymphocytes NK develops a significant cytotoxic activity directed exactly against the tumor. Similar results have been observed with the prolonged administration of these active components in patients with vesicle cancer.
The proteoglucanes may also activate the lymphocytes NK in situ in patients with cancer. Various tests have shown a significant increase of cytotoxic activity of the lymphocytes NK, a significant increase of the interleukina-2 levels and a significant improvement of the relation of T CD4/CD8 cells. This explains their usefulness as immune-stimulants in the cases of cancer and AIDS.
Another way to explain the immune-stimulating action of medicinal mushrooms is the increase of the cytokines of the immune system. Their active components may provoke the secretion of cytokines, including IL-1, IL-2, IL-6, IL-8, TNF (factor of tumor necrosis) and various interferons like 5-120 times the basal levels.
In figure 3, the action mechanism of the glucanes and proteoglucanes of medicinal mushrooms can be seen. Many details of the immune-stimulating action of these mushrooms have not been exactly specified, but their clinical usefulness offers impetus for the continuation of the investigation on their action mechanisms.
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Scientific Evidence:
Numerous studies have confirmed that Maitake has important benefits for the immune system. It promotes the action of macrophages and other cells of the system INME like lymphocytes natural killer (NK) and T-cytotoxic cells (Tc) that attack tumor cells. Maitake also increases the efficiency of immune-competent cells, increasing the levels of interleukins 1, 2 and lymphokines. The final result is an increase of the defense systems against infections, AIDS and cancer. The fractions of Maikate offer specific anti-tumor actions, slowing the growth of colon, lung, gastric, hepatic, prostatic, cerebral tumors and of other organs. (It has to be noted that all references about the fraction-D apply to fraction-MD, because it is the same beta 1,6/1,3 glucanes, derived fro Grifola Frondosa).
Various centers in the United States have begun to treat cancer patients with fraction D and fraction MD. E. g., in February 1998, the North American FDA approved an application as a new investigational drug (IND 54,589) for investigators to conduct a pilot study phase II on the potential effects of fraction D in the treatment of advanced neoplasias of breast and prostate.
The investigators have identified various forms in which Maitake may benefit the cancer patient:
1) Avoiding the malignization of healthy cells;
2) Contributing to the prevention of metastasis;
3) Slowing or detaining the tumor growth;
4) To be used as co-helper of chemotherapy, increasing its positive effects and reducing its secondary effects.
In a study on the preventive potential of Maitake, mice were injected with a carcinogenic substance (3-MCA, methylcholantrene). 15 days after the injection, 10 mice were fed with 0,2 mg of fraction D of Maitake during 15 consecutive days. The control group received a saline solution only. After 30 days, the number of mice with cancer was 30,7% in the group which had received Maitake and 93,2% in the control group. Professor Nanba suggested that fraction D of Maitake has a strong capacity to stimulate the immune system.
In another study, the investigators exposed some mice to a well known carcinogen of the urinary bladder (N-butyl-N'-butanolnitrosoamina; BBN) every day during eight weeks and later the mice were fed with medicinal mushrooms, including Maitake, shiitake and others. All mice treated with BBN developed bladder cancer, but only 46,7% of mice that had received Maitake, developed this type of tumor. Furthermore, Maitake as well as other mushrooms, prevented the depression of the activity of lymphocytes and NK cells.
In a study on the anti-metastasic potential of Maitake, the investigators injected neoplasic cells into the rear pats of mice. Later they divided the mice into three groups: the control group received normal food, while the other two groups received Maitake powder as 20% of their daily food or fraction D intraperitoneally at the rate of 1 mg/kg ten times. After 30 days, 100% of the control group mice had metastasis, while fraction D prevented 91,3% of the total and Maitake powder prevented 81,3% (p<0.01). (See figure 1). |
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In another study, the investigators administered a fraction of purified polysaccharide of Maitake at a rate of 1 mg/kg intraperitoneally, 24 hours after having implanted tumor cells MM-46 of breast cancer; skin carcinoma cells IMC or fibrosarcoma Meth-A cells into the armpit region of male mice. 25 days after the implant, the solid tumors were extracted and were weighted to learn their inhibition of growth. Maitake produced a significant inhibition of tumor growth which was between 25,6% for the fibrosarcoma Meth-A and 49% for the tumor cells.
In another study with a similar design, a fraction of polysaccharides of beta-1,3 glucanes with ramification 6, extracted from Maitake, was tested. This fraction showed significant anti-tumor effects against cells of fibrosarcoma Meth-A and carcinoma cells IMC, but did not inhibit the growth of leukemical cells. Oral doses of fraction D also showed a significant anti-tumor activity against alogenical and singenical tumors.
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In another study, the investigators compared the effects of fraction D and mytomycene (a chemotherapical agent) in mice with tumors. Fraction D alone inhibited the tumor growth more effectively than mytomycene alone (80% vs. 45% respectively). Using fraction D together with mytomycene was even more effective, reaching 98% of tumor growth inhibition. This apparent synergic effect of Maitake and mytomycene is attributed to their different action mechanisms: Maitake stimulates the immune system and mytomycene directly attacks the tumor cells.
In 1994, a group of Chinese investigators published the results of their studies on 63 patients with cancer, where they showed a total effect against solid tumors of over 95% and an effect against leukemia of over 90%.
In 1995, Professor Nanba did some preliminary clinical studies on the use of Maitake as a co-helper of chemotherapy using fraction D in patients with neoplasia of an advanced stage. A total of 165 patients with cancer of stage III - IV, aged between 25 and 65 years, participated in the study and the data were collected with the collaboration of Japanese physicians from hospitals, universities and clinics for the treatment of cancer. These patients received pills with Maitake powder and fraction D or pills with Maitake powder in a dosage between 4 and 6 grams per day, together with chemotherapy. A symptomatic improvement or a regression of approximately 73% of breast cancer and 67% of lung cancer was achieved. In cases of hepatic cancer, 47% responded, but this figure jumped to 73% when chemotherapy was added. 83% of these patients reported pain decrease and 90% experienced an improvement of symptoms related to chemotherapy like: nausea, vomiting, loss of appetite, hair loss, intestinal bleeding and leucopenia. (See figure 2).
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The ingestion of Maitake prevents the development of cancer in 22,2% and the appearance of metastasis in 81,3% of all cases, which suggests that it may contribute to a reduction of cancer risk.
On the other hand, various North American physicians have reported good results with Maitake and in 1998 it was approved as a new drug for investigation purposes, to initiate the pilot studies of the second phase in patients with advanced breast and prostate cancer.
Maitake has been successfully used in breast tumors, liver, lung, prostate, SNC and colon tumors, uterinary fibroadenomas, leukemia, lung metastasis, Hodgkin lymphoma and the syndrome of acquired immune-deficiency.
On the other hand, Maitake increases the effects of the shark cartilage supplement (which inhibits the angiogenesis tumor).
Although it cannot be confirmed that Maitake is a cure for cancer, it maintains the quality of life of the patients and strengthens the immune system which results in a remission of the cancer cells and the improvement of immune parameters without any secondary effects.
Maitake and the Virus of Human Immunodeficiency (VIH)
At the end of the 80s, Japanese investigators determined in a study with animals that oral doses of fraction D improved the lymphocytes T helpers (T helper), the white VIH cells. It was the first clinical sign that Maitake could be a potential treatment for VIH.
In November 1991, a sulphated Maikate fraction proved to be active in preliminary tests of anti-VIH medicaments, conducted by the National Cancer Institute (NCI) of the United States . According to this institution, Maitake showed a significant anti-retroviral activity, depending on the dosage.
Since then, various studies on the immune-modulating effects of Maitake support its use against VIH. Fraction MD was also evaluated in a long term study on humans, with a view to learning about its beneficial potential for patients infected by VIH.
Nanba and his collaborators studied the effects of pills with 6 grams of Maitake and doses of 20 mg of fraction MD with pills of 4 grams, taken daily during one year by 35 seropositive patients. The investigators monitored the number of CD4+ (T helper cells), viral charge, symptoms of VIH infection, presence of secondary diseases and sensation of wellbeing. The effects of the counting of T-helper cells and viral charge was variable: the number of T-helper cells increased in 20 patients, decreased in 8 and was stable in 2. The viral charge decreased in 10 patients, increased in 9 and was stable in 2. Eighty five percent of the patients reported an increase in the sensation of wellbeing related with various symptoms and secondary sicknesses caused by VIH. The investigators concluded that fraction MD acts at various levels: it directly inhibits VIH; it stimulates the immune defense systems against VIH and opportunist sicknesses.
Preliminary unpublished studies suggest that the liquid extract of fraction D, mixed with dimethylsulphoxide, may be used in the treatment of Kaposi sarcoma which accompanies AIDS.
Various North American physicians have reported good results with Maitake and in 1998 it was approved as a new investigative drug to initiate the pilot studies of the second phase with patients with advanced breast and prostate cancer. Maitake also strengthens the effects of the shark cartilagon supplement (which inhibits angiogenesic tumors).
Although it cannot be confirmed that Maitake is a cure for cancer or AIDS, it keeps up the quality of life of the patients and strengthens the immune system, which results in a remission of cancerous cells and an improvement of immunological parameters without any secondary effects.
Other Effects
The Japanese recognize Maitake as a tonic or adaptogene, as a substance which balances the body functions and offers wellbeing, vitality and strength. The physicians who prescribed this medicinal mushroom, reported that it improved the cases of chronical tiredness, candida albican vaginal infections and uterinary fibromas. Studies with Maitake powder and other presentations during the last two decades suggest that it may have an important role in the treatment of other sicknesses.
Diabetes
At least two studies suggest that Maitake has a therapeutic effect against diabetes. In one test, Japanese investigators fed mice with diabetes with some food which contained 20% of Maitake powder during 8 weeks. The test proved the inhibition of an increase of sanguine glucose. The investigators also observed the hypoglycemiacal activity of fraction X, concluding that Maitake is effective to decrease the sanguine glucose in diabetic animals. A later study, done by Kubo and Nanba, also with diabetic mice, proved that Maitake inhibited an increase of sanguine glucose, an effect related with the insulin receptors. The authors suggest that Maitake increases the sensibility for insulin.
Arterial Hypertension
Maitake powder has shown in animal tests to decrease the arterial pressure and to prevent its increase. Feeding rats with Maitake powder (5% of the diet) during 9 weeks, significantly reduced the arterial tension. A similar feeding procedure during 8 weeks, initiated when the mice were 10 weeks old and had established arterial hypertension, was also successful. Maitake prevents the development of hypertension and also reduces elevated tension.
Cholesterol and Triglycerides
Various studies have examined the effects Maitake has on the seric lipids, including cholesterol and triglycerides. In a study published in 1988, hypertense rats were fed with a mixture of 5% Maitake powder which significantly reduced the levels of VLDL and total cholesterol. Another study done on rats fed with a diet of high cholesterol contents, together with 20% of Maitake powder showed that Maitake inhibited the hepatic accumulation of fats and produced a reduction of total cholesterol.
In another study with similar rules, the rats fed with Maitake experienced a significant and prolonged reduction of cholesterol and seric triglycerides, maintaining similar levels of HDL cholesterol.
Hepatopathies
Various studies suggest that Maitake may also be effective to prevent and treat hepatic sicknesses. At the beginning of de 90s, Chinese investigators conducted a pilot study on 32 patients with chronical hepatitis B. At an international symposium in China in 1994, the investigators presented their results to demonstrate that patients who received Maitake showed positive signs of improvement (a decrease of the transaminase values) compared with the patients of the control group.
In another study, a group of rats was fed with a high cholesterol diet and the effects of complementing this diet with 20% of Maitake powder were measured. The investigators showed that Maitake inhibited the accumulation of hepatic fats.
In another study, the investigators fed mice with chronical self-immune hepatic damage, showing a significant improvement.
Obesity
Maitake has some complex B vitamins, ergosterol/provitamin D2, magnesium, potash, calcium, unsaturated fat acids, phosphatidilsesrine and other phospholipids and proteins. Although it does not contain vitamins A or C, there have been identified some substances with chemical properties similar to ascorbic acid. Because Maitake is rich in fibers and low in calories and fats, it has been mentioned as a natural products to control overweight. Animal studies have shown that the daily supply of Maitake may inhibit weight gain. When rats were fed with dry Maitake powder, 20% in weight of a diet high in cholesterol, an increase in weight and corporal fats was significantly inhibited. A similar rule showed an improvement of the lipid metabolism in rats fed with Maitake. At the end of the study, those animals had 24,9% less weight than the control rats. The tests done on hypertense rats fed with Maitake also showed an inhibiting effect on weight gain.
In a clinical study conducted on 30 patients with overweight, the investigators offered daily pills with an equivalent of 200 grams of fresh Maitake during two months. All the patients lost weight without any special diet. The average weight loss was 7 - 13 pounds and of them lost 26,4 pounds. |
Systemic Medicine and Maitake
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Dosage:
We recommend to take 2 - 3 capsules with the meals, three times per day.
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Toxicity / Secondary Effects:
No toxicity has been mentioned in any of the studies with animals or humans. Very seldom, there is soft evacuation which disappears at lowering the dose.
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Contraindictions:
None. Since centuries, Maitake is a daily consumed food in Asian cultures.
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Conclusion:
In Japan and China there is a considerably advanced tendency to integrate immune-stimulating agents in surgery, chemo and radiotherapy for cancer treatment. In these countries, preparations with medicinal mushrooms are a therapeutical resource against cancer since centuries. In Western countries, the proactive handling of cancer has been relegated, despite the failure of the conventional medicine to cure common neoplasias and the access to excellent clinical evidence which supports the use of immunoceutical mushrooms. In the near future, dogmas will disappear to open the way for the immune-therapy with myocotic mushrooms, improving the quality of life and the rate of survival of patients with cancer or AIDS.
One of the frequent death causes of patients with cancer are the metastasis that occur with or without an invasion of the adjacent tissues by tumors. Usually, surgery reduces the tumor mass and chemo and radiotherapy often reduce the tumors and minimize the possibility of being invaded and the metastasis. However, these toxic therapies invariably affect the immune-intelligence of the host and small quantities of malign cells survive the best efforts to eliminate them. The capacity to improve the immune-intelligence to make it act against the tumors and their metastasis, and at the same time the strengthening of the destructive capacity of chemotherapy and the reduction of its effects, makes the immune-therapy with medicinal mushrooms a clinically attractive option for oncologists who really want the best for their patients.
Medicinal mushrooms favorably compare with other modificators of biological replies like: vaccination BCG, OK-432, LAK cells or purified cytosines (like interferons, factor of tumor necrosis or interleukina-2). All these substances are able to cause secondary effects, like fever, shivers, eruptions, edemas, arthralgies, arterial hypotension, congestive cardiac insufficiency or toxicity at the level of the central nervous system. Medicinal mushrooms do not produce any adverse effects and no type of intolerance, which makes them an immunoceutic of first order in cancer treatment. In fact, progressive physicians have used them since many years.
The profiles risk-benefit and cost-benefit of medicinal mushrooms are superior to antineoplasic
and anti-retroviral drugs. Further to the safety of their administration during prolonged periods, they improve the energy levels of the patient, accelerate the recovery of any affected bone marrow, protect and recover hepatic functions, reduce any secondary effects of anti-cancerous and anti-retroviral therapies, and at the same time improve the feeling of wellbeing.
Glucanes and proteoglucanes are receiving respect as effective anti-neoplasic therapies. Controlled double blind studies show that they improve the quality of life of over 70% of cancer patients.
The increase of the survival rate achieved with patients treated for cancer or AIDS with these medicinal mushrooms is of great clinical importance. Used in combinations, they have the potential to prolong the survival.
Maitake offers hope to patients with cancer or AIDS. Its active components contribute to maintain the homeostasis, they are strong immune-stimulants that do not produce self-immune phenomenons. As a dietary supplement, it is safe and offers an almost perfect risk-benefit profile. Medicinal mushrooms are indispensable for any patient with cancer, AIDS or a sickness characterized by immune-depression.
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References
1: Oncol Rep. 2005 Mar;13(3):497-502.
Enhancement of cytotoxicity of NK cells by D-Fraction, a polysaccharide from Grifola frondosa.
Kodama N, Asakawa A, Inui A. Department of Microbial Chemistry, Kobe Pharmaceutical University, Motoyama-kitamachi, Higashinada-ku, Kobe, Japan.
In innate immunity, activated natural killer (NK) cells attack and damage pathogens such as bacteria and virus without restriction by the MHC antigen. NK cells activated by IL-12 have been reported to recognize and kill tumor cells in perforin-mediated apoptosis. We have reported that D-Fraction, a polysaccharide extracted from the maitake mushroom (Grifola frondosa), activates macrophages, dendritic cells, and T cells and inhibits the growth of tumor cells. However, the effects of D-Fraction on NK cell function in the innate immune response are not well known. In the present study, we administered D-Fraction to MM-46 mammary tumor-bearing C3H/HeJ mice intraperitoneally for 3 consecutive days and investigated its effects on the activation and cytotoxicity of NK cells. D-Fraction significantly enhanced the cytotoxicity against NK-sensitive YAC-1 cells and the expression of CD223 on NK cells. D-Fraction also increased the expression of CD86 on macrophages. In addition, the levels of IL-12 in the culture supernatant of whole spleen cells and in serum increased, compared with the control corresponding to an increase in expression of IL-12 receptor betaI on NK cells. These results suggest that D-Fraction enhances the cytotoxicity of NK cells through the production of IL-12 by macrophages activated by D-Fraction.
2: Intern Med. 2004 Aug;43(8):737-40.
Successful treatment of hypersensitivity pneumonitis caused by Grifola frondosa (Maitake) mushroom using a HFA-BDP extra-fine aerosol.
Tanaka H, Tsunematsu K, Nakamura N. Third Department of Internal Medicine, Sapporo Medical University School of Medicine, Chuo-ku, Sapporo, Japan.
We successfully treated a patient with occupational hypersensitivity pneumonitis (HP) caused by Grifola frondosa (Maitake) mushroom spore with an extra-fine aerosol corticosteroid; beclomethasone dipropionate (BDP) dissolved in hydrofluoroalkane-134a (HFA). A 49-year-old woman developed respiratory symptoms 3 months after beginning work on a mushroom farm. She was diagnosed as HP based on radiological and serological findings. Oral prednisolone therapy improved her HP and she returned to the same farm. Her HP relapsed after 5 months, and daily 400 microg of HFA-BDP was administered with gradual improvement. An extra-fine particle inhaled corticosteroid might reach appropriate alveoli to be effective therapy for mild HP.
Publication Types:
• Case Reports
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3: J Med Food. 2004 Summer;7(2):141-5.
Administration of a polysaccharide from Grifola frondosa stimulates immune function of normal mice.
Kodama N, Murata Y, Nanba H. Department of Microbial Chemistry, Kobe Pharmaceutical University, Kobe, Japan. |
We have reported that D-Fraction, a polysaccharide extracted from the edible maitake mushroom (Grifola frondosa), activates immunocompetent cells, thereby eliciting antitumor activity. To extend the application of D-Fraction as a nutritional supplement for healthy people as well as treatment for those with cancer, we investigated the effects of D-Fraction on the immune system in normal C3H/HeJ mice. Splenocytes from mice administered D-Fraction intraperitoneally for 17 consecutive days were cultured, and the culture supernatants were analyzed for nitric oxide (NO) and interleukin (IL)-12 production by antigen-presenting cells (APCs), including macrophages and dendritic cells, and also for the T helper (Th)-1 cytokine interferon (IFN)-gamma and the Th-2 cytokines IL-4 and IL-10. The level of IL-10 as well as those of NO and IFN-gamma were increased by D-Fraction as compared with the control, in which the serum immunoglobulin E level was increased. The results suggest that D-Fraction induced a Th-2 dominant response through the activation of macrophages, resulting in the enhancement of humoral immunity rather than cell-mediated immunity. Furthermore, an increase in the percentage ratio of CD69 and CD89 expression on major histocompatibility complex II(+) cells revealed activation of APCs 4 h after D-Fraction administration. These results indicate that D-Fraction enhances both the innate and adaptive arms of the immune response in normal mice. Therefore, its administration may enhance host defense against foreign pathogens and protect healthy individuals from infectious diseases.
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4: J Ethnopharmacol. 2004 Jul;93(1):75-81.
Effect of medicinal plant extracts on forced swimming capacity in mice.
Jung K, Kim IH, Han D. Food Processing Technology, Korea Food Research Institute, Baekhyun-dong, Bundang-ku, Songnam-si, Kyonggi-do, Republic of Korea. |
The tonic effect of Cordyceps militaris (CM), Paecilomyces japonia (PJ), Phellinus linteus (PL), Ganoderma lucidum (GL), Grifola frondosa (GF), and Panax ginseng (PG) was examined based on the forced swimming capacity and the change of biochemical parameters in ICR mice. The treatment groups were orally administered medicinal plant extracts (500 mg/kg per day), while the control group received distilled water for 4 weeks. The swimming times to exhaustion were longer in the CM, PJ, and GF groups than in the control group (P < 0.05). Plasma TG levels were lower in the treatment groups than in the control group. Plasma glucose levels were not significantly different between the control group and each treatment group except the PG group. Plasma lactate and ammonia levels of the PJ and GF groups were lower than those of the control group (P < 0.05). There were no significant differences in the content of liver and gastrocnemius muscle glycogen between the control group and each treatment group. In conclusion, PJ and GF extracts enhanced the forced swimming capacity of mice by increasing fat utilization and by delaying the accumulation of plasma lactate and ammonia.
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5: Res Commun Mol Pathol Pharmacol. 2002;112(1-4):68-82.
Effects of Maitake mushroom fractions on blood pressure of Zucker fatty rats.
Talpur N, Echard B, Dadgar A. Department of Physiology, Medicine and Pathology, Georgetown University Medical Center, Washington, DC, USA.
A link exists between insulin resistance and many chronic disorders of aging including advancing-age. A safer means to prevent or, at least, slow the erosion of insulin sensitivity would provide a novel approach to better health. We compared the ability of a specific extract labeled fraction SX, as well as whole Maitake powder, fraction ES and fraction D of Maitake to influence SBP and various pertinent biochemical parameters when given orally to Zucker Fatty rats, a model of insulin resistance and type 2 diabetes mellitus. A secondary gain was the ability to ascertain the effects of bitter melon, olive oil, and sesame oil alone and combined with fraction SX to influence SBP. We found that a water-soluble fraction obtained from Maitake mushroom (SX) lowers SBP and fasting blood glucose significantly over the three to six weeks of study. While whole Maitake fraction lowered SBP effectively, the effects on fasting blood sugar were not apparent under the conditions of study. In contrast to fraction SX and fraction D, developed primarily to enhance immunity and suppress tumor development and growth, has essentially no effect on SBP under the conditions examined. An ether soluble fraction designated ES lowers SBP significantly. Interestingly, olive oil, unlike sesame oil, also lowers SBP. Finally, bitter melon and a combination of SX plus bitter melon also lower SBP. We conclude that fraction SX of Maitake mushroom may be useful to treat insulin resistance alone or combined with other natural products such as bitter melon and niacin-bound chromium.
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6: J Med Food. 2003 Winter;6(4):371-7.
Effect of Maitake (Grifola frondosa) D-Fraction on the activation of NK cells in cancer patients.
Kodama N, Komuta K, Nanba H. Department of Microbial Chemistry, Kobe Pharmaceutical University, Kobe, Japan. |
Maitake D-Fraction, extracted from maitake mushroom, has been reported to exert its antitumor effect in tumor-bearing mice by enhancing the immune system through activation of macrophages, T cells, and natural killer (NK) cells. In a previous study, the combination of immunotherapy with the maitake D-Fraction and chemotherapy suggested that the D-Fraction may have the potential to decrease the size of lung, liver, and breast tumors in cancer patients. In the present study, we administered maitake D-Fraction to cancer patients without anticancer drugs, and at the same time NK cell activity was monitored to investigate whether the activity is closely related with disease progression. The numbers of CD4(+) and CD8(+) cells in the peripheral blood were measured in 10 patients, and NK cell activity was assessed using K-562 cells as target cells. Serum soluble interleukin-2 receptor (sIL-2R) levels in three patients and the expression of tumor markers in four patients were determined by enzyme-linked immunosorbent assay. The slight changes observed in the CD4(+) and CD8(+) cell numbers were independent of disease severity or stage as well as serum sIL-2R levels. In contrast, maitake D-Fraction hindered metastatic progress, lessened the expression of tumor markers, and increased NK cell activity in all patients examined. Thus maitake D-Fraction appears to repress cancer progression and primarily exerts its effect through stimulation of NK activity. In addition, we conclude that measurement of NK cell activity may be a useful clinical parameter in monitoring disease progression during and following immunotherapy with maitake D-Fraction.
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7: Mol Cell Biochem. 2003 Oct;252(1-2):369-77.
Effects of niacin-bound chromium, Maitake mushroom fraction SX and (-)-hydroxycitric acid on the metabolic syndrome in aged diabetic Zucker fatty rats.
Talpur N, Echard BW, Yasmin T. Department of Physiology and Biophysics, Georgetown University Medical Center, Washington, DC, USA. |
Previous studies in our laboratories have demonstrated that niacin-bound chromium (NBC), Maitake mushroom and (-)-hydroxycitric acid (HCA-SX) can ameliorate hypertension, dyslipidemias and diabetes mellitus, and therefore may be useful in weight management. In the present study, we used aged, diabetic Zucker fatty rats (ZFR) (70-75 weeks) in order to determine whether NBC, fraction SX of Maitake mushroom (MSX) and 60% (-)-hydroxycitric acid (HCA-SX) from Garcinia cambogia, alone or in combination, can affect certain aspects of the metabolic syndrome. Syndrome X or metabolic syndrome has been described as a concurrence of disturbed glucose and insulin metabolism, overweight and abdominal fat distribution, mild dyslipidemia, and hypertension, which are associated with subsequent development of type 2 diabetes mellitus and cardiovascular disease. Four groups of eight ZFR were gavaged daily with different supplements. For the initial three weeks, the control group of ZFR received only water, the second group received NBC 40 mcg elemental chromium/day, the third group received MSX 100 mg/day and the last group received HCA-SX 200 mg/day. During weeks 4-6, the doses of each treatment were doubled. The control animals lost approximately 50 g body weight (BW) per rat over 6 weeks of treatment, which is characteristic of these animals in declining health. In contrast, eight ZFR receiving NBC lost approximately 9 g BW per rat, while rats consuming MSX lost 16 g BW per rat. However, ZFR receiving HCA-SX simulated the pattern in the control group because these animals lost approximately 46 g BW per rat. The wide individual variations resulted in a lack of statistical significance among groups. Nevertheless, 75% of the ZFR in the control group lost more than 50 g BW over the 6 weeks duration, whereas none of the ZFR receiving NBC, 25% of the ZFR receiving MSX and 57% of the ZFR receiving HCA-SX lost over 50 g BW over the 6 weeks of the study. ZFR in all 3 treatment groups showed significantly lower blood pressures as compared to control, which seemed to be dose related. The general trend was for renal and liver blood parameters, hepatic and renal lipid peroxidation and DNA fragmentation to improve due to the supplementation of these natural products. Treatment of animals with a combination of these three novel supplements resulted in a lower SBP and maintenance of BW compared to control animals. These results demonstrate that elderly diabetics and even aging individuals might benefit from a similar regimen.
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8: Zhong Yao Cai. 2003 Jan;26(1):31-2.
Anti-tumor effect of polysaccharide from Grifola frondosa and its influence on immunological function
Li X, Rong J, Wu M. Department of Food Science and Technology, Huazhong Agricultural University, Wuhan, PR China.
When the polysaccharide from Grifola frondosa (PGF) was taken orally by S180 bearing mice at the dosage of 50-150 mg/kg.d for 9 d, the inhibitory rate to S180 was 27.97%-38.46%. The PGF can also enhance thymus index, the ability of splenic lymphocyte proliferation and formation of antibody in splenic cells, and promote the production of IgM hemolysin significantly in S-180 bearing mice.
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9: Cancer Lett. 2003 Mar 31;192(2):181-7.
Relationship between dendritic cells and the D-fraction-induced Th-1 dominant response in BALB/c tumor-bearing mice.
Harada N, Kodama N, Nanba H. Department of Microbial Chemistry, Kobe Pharmaceutical University, 4-19-1, Motoyama-kitamachi, Higashinada-ku, Kobe, Japan. |
Dendritic cells (DCs) are known to not only induce the activation of T cells, but are also associated with the differentiation of T cells. The D-fraction, a beta-glucan extracted from maitake (Grifola frondosa) which expresses anti-tumor effects by establishing a helper (Th)-1 dominance in BALB/c mice, enhanced IL-12p70 production by DCs, when the ratio of CD8alpha(+) DCs to CD8alpha(-) DCs increased. In addition, examination of the tumor rejection effect of D-fraction-stimulated DCs loaded with tumor antigen revealed that tumor growth is inhibited completely by activating CD4(+) T cells and CD8(+) T cells.
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10: Jpn J Pharmacol. 2002 Dec;90(4):357-60.
A polysaccharide, extract from Grifola frondosa, induces Th-1 dominant responses in carcinoma-bearing BALB/c mice.
Kodama N, Harada N, Nanba H. Department of Microbial Chemistry, Kobe Pharmaceutical University, Japan.
A polysaccharide, designated as the D-fraction, extracted from maitake (Grifola frondosa), was reported to have anti-tumor effects by activating macrophages and T cells in C3H/HeN mice in which a Th-1 dominant response was established. In this study using BALB/c mice in which a Th-2 response is genetically dominant, D-fraction reduced the expression of Th-2 cytokine interleukin (IL)-4 but markedly increased the expression of Th-1 cytokine interferon (IFN)-gamma in CD4(+) T cells and also increased IL-12p70 production as well as IFN-gamma production by antigen-presenting cells (APCs), suggesting that D-fraction promotes the differentiation into Th-1 cells of CD4(+) T cells through enhancement of IL-12p70 production by APCs.
11: Biol Pharm Bull. 2002 Dec;25(12):1647-50.
Effects of D-Fraction, a polysaccharide from Grifola frondosa on tumor growth involve activation of NK cells.
Kodama N, Komuta K, Sakai N. Department of Microbial Chemistry, Kobe Pharmaceutical University, Japan.
Natural killer (NK) cells are directly cytotoxic for tumor cells and play a primary role in regulating immune responses. We monitored levels of NK cell cytotoxic activity in cancer patients receiving D-Fraction extracted from maitake mushrooms (Grifola frondosa). Elevated levels of cytotoxic activity were maintained for one year. To elucidate the mechanisms underlying long-term activation of NK cells during treatment with D-Fraction, we examined tumor volume and levels of IFN-gamma and TNF-alpha in MM46-bearing C3H/HeN mice to which D-Fraction was administered for 19 d. D-Fraction markedly suppressed tumor growth, corresponding with increases in TNF-alpha and IFN-gamma released from spleen cells and a significant increase in TNF-alpha expressed in NK cells. This suggests that the D-Fraction activates NK cells even on the 20th day after treatment. Furthermore, D-Fraction increased macrophage-derived interleukin (IL)-12, which serves to activate NK cells. These results suggest that NK cells are not only responsible for the early effects of D-Fraction on tumor growth, but also for the long-term tumor-suppressive effects of D-Fraction through increased IL-12 released from macrophages.
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12: J Agric Food Chem. 2002 Dec 18;50(26):7581-5.
Cyclooxygenase inhibitory and antioxidant compounds from the mycelia of the edible mushroom Grifola frondosa.
Zhang Y, Mills GL, Nair MG. Bioactive Natural Products Laboratory, Department of Horticulture and National Food Safety and Toxicology Center, Biosystems Engineering, Michigan State University, USA. |
The bioassay-guided isolation and purification of the hexane extract of the cultured mycelia of Grifola frondosa led to the characterization of a fatty acid fraction and three compounds, ergosterol (1), ergostra-4,6,8(14),22-tetraen-3-one (2), and 1-oleoyl-2-linoleoyl-3-palmitoylglycerol (3). The composition of fatty acid fraction was confirmed as palmitic, oleic, and linoleic acids by GC-MS and by comparison with the retention values of authentic samples. The structures of compounds 1-3 were established by spectroscopic methods. The fatty acid fraction and compounds 1-3 showed cyclooxygenase (COX) enzyme inhibitory and antioxidant activities. The inhibition of COX-1 enzyme by the fatty acid fraction and compounds 1-3 at 250 microg/mL were 98, 37, 55, and 67%, respectively. Similarly, COX-2 enzyme activity was reduced by fatty acid fraction and compounds 1-3 at 250 microg/mL by 99, 37, 70, and 4%, respectively. The inhibitions of liposome peroxidation by the fatty acid fraction and compounds 1 and 2 at 100 microg/mL were 79, 48, and 42%, respectively. This is the first report of compounds 2 and 3 from the cultured mycelia of G. frondosa. The COX inhibitory activities of compounds 1-3 are reported here for the first time.
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13: J Altern Complement Med. 2002 Oct;8(5):573-80.
Chemosensitization of carmustine with maitake beta-glucan on androgen-independent prostatic cancer cells: involvement of glyoxalase I.
Finkelstein MP, Aynehchi S, Samadi AA. Department of Urology, New York Medical College, Valhalla, NY, USA. |
OBJECTIVE: To improve the poor efficacy (< 10%) of chemotherapy for patients with hormone-refractory prostate cancer, we investigated a possible cytotoxic effect of carmustine/beta-glucan combination on prostatic cancer PC-3 cells, focusing on a glutathione-dependent detoxifying enzyme, glyoxalase I (Gly-I). METHODS: Carmustine (BCNU) is an anticancer agent and a putative inhibitor of Gly-I, while beta-glucan is a unique, nontoxic polysaccharide extracted from maitake mushrooms. The cytotoxic effects of BCNU or other anticancer agents with beta-glucan on PC-3 cells were assessed by cell-viability testing and Gly-I activity was measured using the spectrophotometric method. RESULTS: BCNU, 5-fluorouracil (5-FU), and methotrexate (MTX) were capable of inducing approximately a 50% reduction in cell viability at 72 hours, while etoposide, cisplatin, and mitomycin C were all ineffective. Only the combination of BCNU (50 micro ;mol) and beta-glucan (60 micro g/mL) exhibited an enhanced cytotoxicity with an approximate 90% cell viability reduction, but little improvement was seen with any combinations of 5-FU, MTX, or beta-glucon. Gly-I assays revealed that such a profound (approximately 90%) cell death was accompanied by an approximate 80% reduction in Gly-I activity by 6 hours. CONCLUSION: This study demonstrates a sensitized cytotoxic effect of BCNU with beta-glucan in PC-3 cells, which was associated with a drastic (approximately 80%) inactivation of Gly-I. Therefore, the BCNU/beta-glucan combination may help to improve current treatment efficacy by targeting Gly-I, which appears to be critically involved in prostate cancer viability.
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14: Mol Cell Biochem. 2002 Aug;237(1-2):129-36.
Antihypertensive and metabolic effects of whole Maitake mushroom powder and its fractions in two rat strains.
Talpur NA, Echard BW, Fan AY. Department of Physiology and Biophysics, Georgetown University Medical Center, Washington, DC, USA. |
Maitake mushroom has been reported to favorably influence hypertension and diabetes mellitus. The purpose of this study was to compare the effects of whole Maitake mushroom powder and two extracts designated as ether soluble (ES) and water soluble (WS) on Zucker fatty rats (ZFR), a model of insulin resistance, and on spontaneously hypertensive rats (SHR), a model of genetic hypertension. In the initial study, we followed four groups of eight ZFR and SHR receiving special diets: a baseline diet (BD), BD + whole Maitake mushroom powder (20% w/w), BD + fraction ES (0.10% w/w), and BD + WS (0.22% w/w). Different effects of these dietary regimens on the 2 rat strains were found. At 35 days, only consumption of the ES diet significantly decreased systolic BP (SBP) in SHR (average 197 vs. 176 mm Hg, p < 0.001), while in ZFR only the groups consuming the whole Maitake and WS diets showed significantly decreased SBP (138 vs. 120-125 mm Hg, p < 0.001). A challenge test with losartan (an angiotensin II receptor blocker) indicates that angiotensin II does not play a major role in SBP regulation of ZFR, but does in SHR where consumption of ES relative to other groups significantly lowered activity of this system. In SHR, glucose, cholesterol, circulating insulin and HbA1C were virtually similar among all dietary groups; but whole Maitake (-22%), ES (-120%) and WS (-80%) diets were associated with decreased triglycerides, and the ES diet with lowered serum creatinine (-29%). In ZFR, circulating insulin and HbA1C were significantly decreased in the whole Maitake powder and ES groups, and tended to be lower in the WS group compared to control. In the ensuing studies, we gavaged ZFR once daily with water (control), 44 mg fraction WS, or 44 mg fraction WS plus 100 microg niacin-bound chromium (NBC). Oral gavage of WS clearly lowered SBP and circulating glucose concentrations, more so with the addition of chromium. We conclude that the examined forms of Maitake mushroom have antihypertensive and antidiabetic potential which differ among rat strains. The ES fraction may decrease SBP in SHR via alteration in the renin-angiotensin system.
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15: Altern Med Rev. 2002 Jun;7(3):236-9.
Can maitake MD-fraction aid cancer patients?
Kodama N, Komuta K, Nanba H. Department of Microbial Chemistry, Kobe Pharmaceutical University, Kobe, Japan.
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Maitake mushroom (Grifola frondosa) MD-fraction containing beta-1,6 glucan with beta-1,3 branched chains has previously exhibited strong anticancer activity by increasing immune-competent cell activity.1,2 In this non-random case series, a combination of MD-fraction and whole maitake powder was investigated to determine its effectiveness for 22- to 57-year-old cancer patients in stages II-IV. Cancer regression or significant symptom improvement was observed in 58.3 percent of liver cancer patients, 68.8 percent of breast cancer patients, and 62.5 percent of lung cancer patients. The trial found a less than 10-20 percent improvement for leukemia, stomach cancer, and brain cancer patients. Furthermore, when maitake was taken in addition to chemotherapy, immune-competent cell activities were enhanced 1.2-1.4 times, compared with chemotherapy alone. Animal studies have supported the use of maitake MD-fraction for cancer.
Publication Types:
• Case Reports
• Review
• Review, Tutorial
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16: Biol Pharm Bull. 2002 Apr;25(4):536-40.
Effect of maitake (Grifola frondosa) D-fraction on the control of the T lymph node Th-1/Th-2 proportion.
Inoue A, Kodama N, Nanba H. Department of Microbial Chemistry, Kobe Pharmaceutical University, Japan.
We have already reported that the D-Fraction, a beta-glucan extracted from the fruiting body of the maitake mushroom (Grifola frondosa), activates cellular immunity and expresses anti-tumor effects. In this study we investigated the anti-tumor functions of D-Fraction in relation to its control of the balance between T lymphocyte subsets Th-1 and Th-2. D-Fraction decreased the activation of B cells and potentiated the activation of helper T cells, resulting in enhanced cellular immunity. It also induced the production of interferon (IFN)-gamma, interleukin (IL)-12 p70, and IL-18 by whole spleen cells and lymph node cells, but suppressed that of IL-4. These results suggest that D-Fraction establishes Th-1 dominance which induces cellular immunity in the population that was Th-2 dominant due to carcinoma.
17: J Exp Clin Cancer Res. 2001 Dec;20(4):591-7.
Nitric oxide-mediated antitumor activity induced by the extract from Grifola frondosa (Maitake mushroom) in a macrophage cell line, RAW264.7.
Sanzen I, Imanishi N, Takamatsu N. Dept. of Clinical Nursing, Faculty of Medicine, Toyama Medical and Pharmaceutical University, Sugitani, Japan.
We have investigated D-fraction (MDF) extracted from Grifola frondosa (Maitake mushroom) on the inducible nitric oxide synthase (iNOS)-mediated nitric oxide (NO) production in RAW264.7 (RAW) cells, a murine monocyte/macrophage cell line, with special reference to antitumor activity of MDF against human hepatoma-derived huH-1 cells. MDF could induce iNOS mRNA expression in RAW cells in a dose range of more than 30 microg/ml, but the effect of 10 microg/ml of MDF was negligible. The iNOS mRNA expression induced by 100 microg/ml of MDF was 6 hrs later, but lasted for a longer time than that of lipopolysaccharide (LPS), a representative iNOS inducer. Although iNOS mRNA levels in MDF-stimulated cells were almost equal to LPS-stimulated cells at the peak time, the cumulative amount of nitrite was only about 50% compared with that of LPS-treated cells. When huH-I cells were cultured in MDF containing media in a 24-well plate with inserted porous bottom in the presence or absence of RAW cells, the viability of huH-1 cells decreased significantly only in the presence of RAW cells in MDF dose-dependent manner. This antitumor activity of RAW cells in the presence of MDF was abolished or attenuated by the addition of L-NAME, a NOS inhibitor, confirming that this phenomenon is due to iNOS-mediated NO production by RAW cells, but not direct cytotoxic activity of MDF against huH-1 cells. These data suggest that MDF is a novel inducer for iNOS which contributes at least in part to antitumor activity of MDF.
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18: Diabetes Obes Metab. 2002 Jan;4(1):43-8.
Effects of a water-soluble extract of maitake mushroom on circulating glucose/insulin concentrations in KK mice.
Manohar V, Talpur NA, Echard BW. Department of Physiology, Georgetown University Medical Center, Washington, DC, USA. |
AIM: We examined benefits of a water-soluble extract of maitake mushroom designated as Fraction X (FXM) on the glucose/insulin metabolism of insulin-resistant KK mice, and compared the results of FXM with those of a sulphonylurea, Glipizide. DESIGN: In several acute studies, insulin-resistant KK mice were gavaged with a single dose of varying concentrations of FXM, or a single dose of one concentration of the oral hypoglycaemic drug, Glipizide. In the one chronic study, KK mice were gavaged with FXM, Glipizide, or an equal volume of isotonic saline (baseline control) twice daily. Retro-orbital blood was drawn on the morning of the 4th and 7th days before the early gavage. Blood glucose was measured by routine laboratory procedures, and serum insulin was estimated by a radioimmunoassay (RIA) assay developed specifically for rodents. RESULTS: At a dose of FXM (140 mg/mouse), a statistically significant lowering of circulating glucose concentrations was again seen at 8-12 h and 16-18 h after oral gavage. The lowering approximated 25% of the original concentration. Oral gavage of Glipizide resulted in statistically significantly lower values of circulating glucose (25-37% lower compared with baseline) at 8-24 h post dosing. In the chronic study, the circulating concentrations of glucose and insulin of mice taking 140 mg FXM per day were decreased significantly at days 4 and 7. CONCLUSIONS: FXM, a natural extract obtained from maitake mushroom, favourably influences glucose/insulin metabolism in insulin-resistant KK mice. The lowering of both circulating glucose and insulin concentrations suggests that FXM works primarily by enhancing peripheral insulin sensitivity.
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19: Zhonghua Wai Ke Za Zhi. 1999 Aug;37(8):464-5.
Prevention of postoperative recurrence of bladder cancer: a clinical study
Yang D, Li S, Wang H. Department of Urolagy, Jinan General Hospital of People's Liberation Army, Jinan, PR China.
OBJECTIVE: To lower postoperative recurrence rate of bladder cancer, the prophylactic effects of five kinds of method on bladder cancer were evaluated. METHODS: Between 1982 and 1997, 313 patients after TURBT or partial cystectomy were followed up for 2 to 15 years (average 7.6 years). These patients were divided into six groups: BCG, mytomycin C (MMC), thiotepa, Chinese herb medicine Zhuling (Grifola umbellata pilat), afterloading brachytherapy and control group. The prophylactic effects of them on postoperative recurrence of bladder cancer was evaluated. RESULTS: During the follow-up, the recurrence rates were 35.1% in BCG group, 34.9% in Zhuling group, 41.7% in MMC group, 52.6% in thiotepa group, 64.7% in control group, respectively. 25 high-risk patients with invading or multiple bladder cancer were treated by afterloading brachytherapy. They were followed up from 12 to 42 months, with a recurrence rate being 24.0%. CONCLUSIONS: The prophylactic effect of Zhuling and BCG on bladder cancer recurrence was better than MMC. The vale of thiotepa was not significant. The afterloading brachytherapy was of great vale to invading or recurrent, multiple bladder cancer.
20: Jpn J Pharmacol. 2001 Dec;87(4):327-32.
Addition of Maitake D-fraction reduces the effective dosage of vancomycin for the treatment of Listeria-infected mice.
Kodama N, Yamada M, Nanba H. Department of Microbial Chemistry, Kobe Pharmaceutical University, Japan.
Maitake D-fraction, beta1,6-glucan having beta1,3-branches, has been reported to activate the immune system of the host. To elucidate whether the D-fraction can reduce the clinical effective dosage of antibiotics in the treatment of opportunistic bacterial infection, we examined the effects of D-fraction on the treatment of Listeria monocytogenes-infected mice in combination with vancomycine (VCM), the only antibiotic used for methicillin-resistant Staphylococcus aureus (MRSA). Listeria-infection was introduced by its inoculation into the abdominal cavity of mice. Without treatment, all inoculated mice died within 3 days after the inoculation. In contrast, in the mice treated with combined therapy of D-faction (10 mg/kg per day) and VCM (10 mg/kg per day), the survival rate was maintained at 60% on the 10th day after the inoculation, which was superior to that of mice treated with VCM alone (10 mg/kg per day). To investigate the mechanism underlying the reinforcement of VCM treatment by the D-fraction, the activities of macrophages and splenic T cells of Listeria-infected mice were evaluated. In mice administered with both D-fraction and VCM, macrophages produced 2.7 times as much interleukin-1 as that of non-treated control mice. The bactericidal activity of splenic T cells was also enhanced by 2.6 times of that of non-treated control mice. These results indicate that D-fraction activates immuno-competent cells, induced cytokine production, and consequently enhanced the bactericidal activities of the splenic T cells against Listeria monocytogenes, suggesting the clinical benefit of D-fraction in the case of anti-bacterial treatment for patients with high risks.
21: Biosci Biotechnol Biochem. 2001 Sep;65(9):1993-2000.
Relationship between solubility of grifolan, a fungal 1,3-beta-D-glucan, and production of tumor necrosis factor by macrophages in vitro.
Ishibashi K, Miura NN, Adachi Y. Laboratory for Immunopharmacology for Microbial Products, School of Pharmacy, Tokyo University of Pharmacy and Life Science, Hachioji, Japan.
Grifolan, GRN, is a fungal antitumor beta-glucan isolated from Grifola frondosa. Various studies suggested that the underlying mechanism of the antitumor activity of GRN is strongly related to immune modulation. In the previous publication (Adachi et al., 1994; Okazaki et al., 1995), we have shown that GRN activates macrophages to produce tumor necrosis factor (TNF) in vitro. In this study, the structural unit essential to produce TNF was examined by chemical modifications of GRN. GRN suspended in distilled water was treated at 150 degrees C for up to 3 h. Addition of the resulting turbid solution to the RAW 264.7 macrophage-like cell line produced TNF, and the relative activity was diminished in relation to the heat treatment period. The fractions with a heating period longer than 15 min did not show any activity. After centrifugation of the resulting solution, significant activity was shown by precipitate fractions, suggesting that the insoluble form of GRN is important for TNF production. Interestingly, the precipitate fraction obtained from 9 min of treatment also had significant activity. In addition, admixing the soluble fraction with the particles significantly inhibited the TNF production. In contrast to these observations, the high-molecular-mass subfraction of the soluble fraction prepared by ultrafiltration produced significant amounts of TNF. Similar phenomena were shown with sodium hydroxide treatment and dimethylsulfoxide treatment. These facts strongly suggested that insoluble as well as a high molecular mass soluble form of GRN are required for TNF production by macrophages.
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22: Cancer Lett. 2001 Oct 30;172(2):193-8.
Effects of maitake (Grifola frondosa) D-Fraction on the carcinoma angiogenesis.
Matsui K, Kodama N, Nanba H. Department of Microbial chemistry, Kobe Pharmaceutical University, Higashinada-ku, Kobe, Japan. |
We have reported that D-Fraction extracted from maitake (Grifola frondosa), activates immune competent cells, and indicates anti-tumor activities. The D-Fraction was observed to induce angiogenesis in vivo and to enhance the proliferation capability and migration capability of human vascular endothelial cell in vitro. The D-Fraction also increased plasma vascular endothelial growth factor (VEGF) concentration significantly. Also VEGF and TNF-alpha production by the activated peritoneal macrophages were enhanced. These results suggest that the anti-tumor activity of the D-Fraction is not only associated with the activation of the immuno-competent cells but also possibly related to the carcinoma angiogenesis induction.
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23: Exp Biol Med (Maywood). 2001 Sep;226(8):758-65.
Cholesterol-lowering effects of maitake (Grifola frondosa) fiber, shiitake (Lentinus edodes) fiber, and enokitake (Flammulina velutipes) fiber in rats.
Fukushima M, Ohashi T, Fujiwara Y. Department of Bioresource Science, Obihiro University of Agriculture and Veterinary Medicine, Hokkaido, Japan. |
The effects of mushroom fibers on serum cholesterol and hepatic low-density lipoprotein (LDL) receptor mRNA in rats were investigated. Rats were fed a cholesterol-free diet with 50 g/kg cellulose powder (CP), 50 g/kg maitake (Grifola frondosa) fiber (MAF), 50 g/kg shiitake (Lentinus edodes) fiber (SF), or 50 g/kg enokitake (Flammulina velutipes) fiber (EF) for 4 weeks. There were no significant differences in the body weight, food intake, liver weight, cecum weight, and cecum pH among the groups. Cecal acetic acid, butyric acid, and total short-chain fatty acid (SCFA) concentrations in the SF and EF groups were significantly higher than those in the other groups. The serum total cholesterol concentration in the CP group was significantly higher than that in the MAF and EF groups. The very LDL (VLDL) + intermediate-density lipoprotein (IDL) + LDL-cholesterol concentration in the CP group was significantly higher than that in the MAF, SF, and EF groups, whereas the high-density lipoprotein (HDL)-cholesterol concentration in the EF group was significantly lower than that in the other groups at the end of the 4-week feeding period. The hepatic LDL receptor mRNA level in the EF group was significantly higher than that in the CP group. The fecal cholesterol excretion in the MAF, SF, and EF groups was significantly higher than that in the CP group. The results of this study demonstrate that MAF and EF lowered the serum total cholesterol level by enhancement of fecal cholesterol excretion, and in particular, by enhancement of hepatic LDL receptor mRNA in EF group.
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24: J Nutr Sci Vitaminol (Tokyo). 2001 Feb;47(1):57-63.
Maitake (Grifola frondosa) improve glucose tolerance of experimental diabetic rats.
Horio H, Ohtsuru M. Department of Food Science and Nutrition, Faculty of Home Economics, Nishikyushu University, Saga, Japan.
We have previously reported that rats with diabetes induced by injecting streptozotocin into neonates showed remarkably lower blood glucose, urine volume, and glucosuria after administration of Maitake (Grifola frondosa). In the present study, we investigated the effects of Maitake on insulin concentration, organ weight, serum composition, and islets of Langerhans in streptozotocin-induced diabetic rats using the same method. The diabetic rats were produced by injecting 80 mg/kg B.W. streptozotocin into 2-d-old neonates. From the age of 9 wk, the rats were given experimental diets for 100 d. The diabetes and control groups were given either diets containing 20% Maitake (DM and CM groups) or control diets (D and C groups). During administration of the experimental diets, we measured body weight, food intake, amount of feces, and serum insulin concentration at glucose loading. The glucose tolerance test was performed at the 10th week after the start of the experimental diets. The D group had an initial fasting blood glucose of 225+/-49 mg/dL, and a maximum blood glucose of 419+/-55 mg/dL at 60 min. In the DM group, however, the initial fasting blood glucose was 170+/-23 mg/dL, and the maximum blood glucose was 250+/-41 mg/dL at 15 min. Both values were markedly lower than those in the D group (p<0.05). The insulin concentration at 15 min. after glucose loading in the DM group was 41+/-16 microU/mL, which was significantly higher than that in the D group (15+/-7 microU/mL) (p<0.05). After the 100-d experimental period, blood samples were collected. The fructosamine level was significantly lower in the DM group (152+/-21 mmol/L) than in the D group (185+/-13 mmol/L). The concentration of 1.5-A.G. (1.5-anhydro glucitol) was significantly higher in the DM group (9.33+/-2.42 microg/mL) than in the D group (1.33+/-0.52 microg/mL). Observation of insulin antibody stain in the Langerhans cells of the pancreas using ABC method showed a decrease insulin antibody stain in the D group. The cells of the DM group were stained more darkly than those of the D group. From these results, we postulated that the bioactive substances present in Maitake can ameliorate the symptoms of diabetes.
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25: Altern Med Rev. 2001 Feb;6(1):48-60.
Maitake extracts and their therapeutic potential.
Mayell M.
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Maitake (Grifola frondosa) is the Japanese name for an edible fungus with a large fruiting body characterized by overlapping caps. It is a premier culinary as well as medicinal mushroom. Maitake is increasingly being recognized as a potent source of polysaccharide compounds with dramatic health-promoting potential. The most recent development is the MD-fraction, a proprietary maitake extract its Japanese inventors consider to be a notable advance upon the preceding D-fraction. The D-fraction, the MD-fraction, and other extracts, often in combination with whole maitake powder, have shown particular promise as immunomodulating agents, and as an adjunct to cancer and HIV therapy. They may also provide some benefit in the treatment of hyperlipidemia, hypertension, and hepatitis.
Publication Types:
• Review
• Review, Tutorial
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26: Jpn J Pharmacol. 2000 Nov;84(3):293-300.
Effects of maitake (Grifola frondosa) polysaccharide on collagen-induced arthritis in mice.
Shigesue K, Kodama N, Nanba H. Department of Microbial Chemistry, Kobe Pharmaceutical University, Japan.
We recently reported the anti-hepatitis effect of a polysaccharide, designated as the D-fraction, extracted from maitake. Its effect includes immuno-regulating activities. We investigated the effect of the glucan in collagen-induced arthritis (CIA). The D-fraction was administered to CIA mice for 30 consecutive days. Arthritis development was observed from the 4th day after the second immunization. The D-fraction did not have any influence on anti-type II collagen antibodies in blood serum or activated B cells. To determine how cellular immunity may be involved in the development of CIA, ratios of CD4+ T cells and their activated form in the axillary and inguinal lymph node T cells were detected by flow cytometry analysis. The ratios were not different between the D-fraction group and the control group. However, interleukin-1beta, granulocyte-macrophage colony-stimulating factor and tumor necrosis factor-alpha productions from splenic macrophages were significantly increased to 2.0, 4.7 and 1.9 times the control group level, respectively. The ratio of macrophages in the whole spleen cells was 2.3 times that of the control group, and their migrating ability was 1.9 times higher. Based on these results, we concluded that the arthritis development induced by D-fraction administration is attributable to the activation of splenic macrophages.
27: Biosci Biotechnol Biochem. 2000 Sep;64(9):2001-4.
Suppression of D-galactosamine-induced liver injury by mushrooms in rats.
Lee EW, He P, Kawagishi H. Department of Applied Biochemistry, Faculty of Agriculture, Shizuoka University, Japan.
Six species of edible mushroom were found to suppress D-galactosamine-induced enhancement of plasma alanine and aspartate aminotransferase activities when powdered mushrooms were added to the diet (5%) and fed to rats for 2 wk. Grifola frondosa exhibited the most potent effect in a dose-dependent manner. A significant effect was observed only from the water-soluble low-molecular-weight fraction of G. frondosa. The results indicate that several mushrooms possess a protective effect against liver injury induced by D-galactosamine.
28: Mol Urol. 2000 Spring;4(1):7-13.
Induction of apoptosis in human prostatic cancer cells with beta-glucan (Maitake mushroom polysaccharide).
Fullerton SA, Samadi AA, Tortorelis DG. Department of Urology, New York Medical College, Valhalla, New York, USA.
PURPOSE: To explore more effective treatment for hormone-refractory prostate cancer, we investigated the potential antitumor effect of beta-glucan, a polysaccharide of the Maitake mushroom, on prostatic cancer cells in vitro. MATERIALS AND METHODS: Human prostate cancer PC-3 cells were treated with various concentrations of the highly purified beta-glucan preparation Grifron-D(R) (GD), and viability was determined at 24 h. Lipid peroxidation (LPO) assay and in situ hybridization (ISH) were performed to unravel the antitumor mechanism of GD. RESULTS: A dose-response study showed that almost complete (>95%) cell death was attained in 24 h with GD > or = 480 microg/mL. Combinations of GD in a concentration as low as 30 to 60 microg/mL with 200 microM vitamin C were as effective as GD alone at 480 microg/mL, inducing >90% cytotoxic cell death. Simultaneous use with various anticancer drugs showed little potentiation of their efficacy except for the carmustine/GD combination (approximately 90% reduction in cell viability). The significantly (twofold) elevated LPO level and positive ISH staining of GD-treated cells indicated oxidative membrane damage resulting in apoptotic cell death. CONCLUSION: A bioactive beta-glucan from the Maitake mushroom has a cytotoxic effect, presumably through oxidative stress, on prostatic cancer cells in vitro, leading to apoptosis. Potentiation of GD action by vitamin C and the chemosensitizing effect of GD on carmustine may also have clinical implications. Therefore, this unique mushroom polysaccharide may have great a potential as an alternative therapeutic modality for prostate cancer.
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29: Altern Med Rev. 2000 Feb;5(1):4-27.
The use of mushroom glucans and proteoglycans in cancer treatment.
Kidd PM.
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Immunoceuticals can be considered as substances having immunotherapeutic efficacy when taken orally. More than 50 mushroom species have yielded potential immunoceuticals that exhibit anticancer activity in vitro or in animal models and of these, six have been investigated in human cancers. All are non-toxic and very well tolerated. Lentinan and schizophyllan have little oral activity. Active Hexose Correlated Compound (AHCC) is poorly defined but has shown early clinical promise. Maitake D-Fraction has limited proof of clinical efficacy to date, but controlled research is underway. Two proteoglycans from Coriolus versicolor - PSK (Polysaccharide-K) and PSP (Polysaccharide-Peptide - have demonstrated the most promise. In Japanese trials since 1970, PSK significantly extended survival at five years or beyond in cancers of the stomach, colon-rectum, esophagus, nasopharynx, and lung (non-small cell types), and in a HLA B40-positive breast cancer subset. PSP was subjected to Phase II and Phase III trials in China. In double-blind trials, PSP significantly extended five-year survival in esophageal cancer. PSP significantly improved quality of life, provided substantial pain relief, and enhanced immune status in 70-97 percent of patients with cancers of the stomach, esophagus, lung, ovary, and cervix. PSK and PSP boosted immune cell production, ameliorated chemotherapy symptoms, and enhanced tumor infiltration by dendritic and cytotoxic T-cells. Their extremely high tolerability, proven benefits to survival and quality of life, and compatibility with chemotherapy and radiation therapy makes them well suited for cancer management regimens.
Publication Types:
• Review
• Review, Tutorial
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30: J Nutr Sci Vitaminol (Tokyo). 1999 Jun;45(3):385-9.
Effect of maitake (Grifola frondosa) water extract on inhibition of adipocyte conversion of C3H10T1/2B2C1 cells.
Nakai R, Masui H, Horio H. Department of Food Science and Nutrition, School of Human Environmental Science, Mukogawa Women's University, Nishinomiya, Japan.
We investigated the effect of maitake (Grifola frondosa) water extract on inhibiting the conversion of C3H10T1/2B2C1 cells into adipocytes. Maitake water extract was fractionated by molecular sieve. Heat-labile compounds strongly inhibiting adipocyte conversion proved to occur in fractions of molecular weight of more than 10,000 on the basis of activity measurement of glycerol-3-phosphate dehydrogenase.
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31: Proc Soc Exp Biol M | | | |
