Agaricus blazei murill originally from the rainforests of Brazil is one such mushroom. Agaricus blazei murill is now considered one of the most important medicinal mushrooms in Japan and China. But why so popular? And important? Functional Uses of Agaricus blazei murill.
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The medicinal mushroom Agaricus blazei Murill from the Brazilian rain forest has been used in traditional medicine and as health food for the prevention of a range of diseases, including infection, allergy, and cancer. Other scientists and we have examined whether there is scientific evidence behind such postulations.
Agaricus subrufescens Peck already described in , and Agaricus brasiliensis Wasser [ 1 ] Figure 1 , of Brazilian rain forest origin is used in traditional medicine against cancer and various diseases [ 2 , 3 ]. AbM is also shown to contain agaritine and ergosterol provitamin D2 that is found to induce apoptosis in leukemic cells [ 10 ] and inhibit tumor-induced angiogenesis [ 11 ], respectively, as well as isoflavonoids with potent hypoglycemic action that could be useful against diabetes mellitus [ 12 ].
AbM is reported to have antitumor properties in mouse models of fibrosarcoma, myeloma, ovarian, lung, and prostate cancer, and in human studies against gynecological cancer increased NK cell activity and quality of life and leukemia [ 13 ]. Agaricus blazei Murill. Photo NutriCon.
The mushroom is cultivated commercially for the health food market in Japan, China, and Brazil. The mixed mushroom extract also protected against IgE-mediated allergy in a mouse model when given p. In supernatants of cultured spleen cells from the sacrificed AbM-treated mice, there was an increased T-helper cell 1 response relative to the allergy-inducing Th2 response.
The observation fits with the reduced specific serum IgE levels in these animals and shows that also adaptive immunity is engaged by the mushroom. It is previously known that patients with advanced cancer have malfunctional Th1 cells and a Th2-skewed immune system [ 19 ]. From [ 14 ], permission granted for republication by Scand J Immunol, where the figure was originally published.
Similar results were found if AbM extract or PBS was given 3 weeks after the allergen immunization not shown, please see [ 16 ]. IgG2a antiovalbumin levels Th1 response tended to show the opposite result not shown. From [ 16 ], previously published by a BMC journal, which allows reuse. The outcome of this experiment, actually done in but not published until , was the basis for choosing AndoSan then called AbM extract A in our further studies.
Synergies between components from the three mushrooms in the said extract may explain its enhanced efficacy against sepsis. Hence, in contrast to the exposed but healthy individuals, the tuberculosis patients represent a selected group, which is not prone to the tubercle bacilli's strong ability to elicit Th1-type cellular immune responses, for example, the normal reaction to the BCG vaccine.
In a human phase I study in 15 healthy volunteers, we recently found no side effects after intake of the AbM-based AndoSan extract [ 23 , 24 ]. In particular, there were no significant changes in general blood parameters and no negative effects on kidney, liver, or pancreas function. This agrees with a toxicity study over two years in rats [ 25 ], which rather found that animals ingesting the highest AbM concentration lived the longest, presumably due to reduced cancer development.
In the mentioned phase I study, AbM extract had an anti-inflammatory effect as shown by significantly reduced levels of proinflammatory cytokines. Although this is contrary to our in vitro findings of increased production of proinflammatory cytokines by monocytes, monocyte-derived DC MDDC , and human umbilical vein endothelial cells HUVEC , we did, as a consequence of the phase I trial, conduct a clinical pilot study at our hospital on patients with the inflammatory bowel diseases, ulcerative colitis and Crohn's disease.
The result was a significant decrease in plasma levels of proinflammatory cytokines after 12 days of AndoSan intake orally and also decreased levels of the inflammatory marker calprotectin in feces of ulcerative colitis patients [ 24 ]. This anti-inflammatory property of AbM may also be of importance for the mushroom's therapeutic effect on allergy and asthma in mouse models [ 18 , 21 ], both of which are inflammatory conditions, and it may bear promise for use against autoimmune diseases.
In addition, it may explain some of AbM's antitumor effects discussed below. Days 0 and 12 after stimulation are depicted by the first and second bars from the left, respectively. The P values between the bar graphs compare with the cytokine levels at day 0 prior to the intake of AndoSan.
From [ 24 ] where the data was part of scatter plots in Scand J Immunol. The reason for the forceful and swift engagement of innate immunity when encountering an edible and harmless mushroom, such as AbM, is its sharing of pathogen-associated molecular patterns PAMP with other highly poisonous species.
Such mushrooms and fungi are usually a health threat due to the action of their toxins, for example, muscimol from Amanita muscaria and the vasoconstrictor ergotamine from Claviceps purpurea , or invasion in immunodeficient patients e. One can exploit this immune reaction by using an innocent mushroom such as Agaricus blazei M to enhance the body's protection against serious diseases.
This demonstrates that AbM also affects EC, which are important parttakers in the innate immune response. In a human study, AbM has been shown to increase NK cell activity in cancer patients [ 31 ].
Another important group of receptors on macrophages and other innate immune cells are cytosolic NOD nucleotide-binding and oligomerization domain- like receptors NLR. It is also known that AbM can activate the alternative pathway of complement [ 34 ], giving binding of the CR3 ligand, iC3b, to particulate AbM and thus contribute to the AbM engagement of the phagocytic CR3. Moreover, the formation of complement activation split products and chemotaxins—C3a and C5a—when also the terminal complement pathway is activated will lead to their binding to C3a and C5a CD88 receptors, respectively, and chemotaxis of the immune cells towards a C3a and C5a gradient and hence towards the AbM source.
Another possibility is direct uptake of or stimulation by such substances of DC via their processes into the gastrointestinal lumen or by intestinal macrophages that may fragment the glucans for transport to the bone marrow and reticuloendothelial system for further release and stimulation of other immune cells [ 35 ]. Previously, AbM has in fact been shown to stimulate endothelial cells in vitro [ 29 ]. Sorimachi et al. Interestingly, also a low-molecular-weight polysaccharide isolated from AbM has been reported to suppress tumor growth and angiogenesis in vivo [ 38 ].
Pyroglutamate is found to be another such small substance [ 39 ]. Most probably the mushroom extract also affects the intestinal flora, which comprises 10 times more bacteria than cells in our entire body.
Bacteria in the gut are known to produce essential vitamins and so forth, for example, bacteria that can ferment soy beans and produce K2 vitamin that is important for calcium metabolism [ 49 ].
It is probable that also intestinal bacteria either produce metabolites during digestion of AbM extract or produce analytes after themselves being stimulated by AbM. Such molecules may be biologically active after uptake from the gut and may affect the host.
At our Department of Cellular Therapy, we construct autologous DC vaccines for clinical trials against various human cancers, by electroporating isolated cancer mRNA into dendritic cells harvested from the same patients.
Benko et al. In line with this school of thought, we are currently examining whether the above AbM extract may be used as immune adjuvant in such anti-cancer DC vaccines, similar to studies on DNA vaccines in the mouse against hepatitis B virus and mouth-and-foot diseases [ 51 , 52 ].
In these vaccines, AbM was found to increase levels of antigen-specific antibodies as well as to promote proliferation of T cells, illustrating engagement of adaptive immunity. Figure 5 shows a cartoon of the proposed role of AbM in immune system modulation and the resulting disease control. Role of the mushroom Agaricus blazei Murill in immune system modulation and disease control. In Figure 6 , the balance between the different Th responses is depicted as the Ying and Yang of adaptive immunity.
In the other patients with ulcerative colitis, which is proposed to have a Th2-type autoimmune pathogenesis, we found that the IL-4 and IL levels tended to decrease, although not statistically significantly, after AndoSan's intake [ 24 ]. The Ying and Yang of adaptive immunity. There is a balance between the Th responses in such a way that Th1 inhibits Th2, which inhibits Th17 and which again inhibits the Treg response. The regulation by T reg cells results in immunosuppression and tolerance.
As mentioned, the Agaricus mushroom is reported to inhibit various tumors [ 10 ], including hematological cancers such as myeloma in a recent mouse model [ 43 ] and leukemia in a human study [ 42 ]. One proposed mechanism behind the antitumor effects of AbM is the induction of apoptosis in tumor cells, which is demonstrated in vitro [ 40 ].
This is confirmed by the microarray finding of increased expression of genes inducing apoptosis as well as inhibition of cell division [ 46 ] in PBMC from patients with hepatitis C virus infection who drank AbM extract for 1 week. There is a well-established connection between inflammation and tumorigenesis [ 56 ], and it is known that organs with chronic inflammation are prone to cancer, for example, the colon in inflammatory bowel diseases, the pancreas after chronic pancreatitis, and the liver secondary to chronic viral hepatitis.
Hence, both the anti-inflammatory [ 23 , 24 ] and anti-infection [ 14 , 15 ] properties of AbM that we have disclosed may contribute to the mushroom's antitumor activity. Currently at our hematological department, we are conducting a placebo-controlled, double-blinded phase II trial in patients with multiple myeloma, who have been drinking the AbM-based AndoSan extract as a supplementary treatment.
These patients are subjected to standard high-dose chemotherapy and autologous hematopoietic stem cell transplantation after the harvesting of the cells at our Department of Cellular Therapy. Patients with multiple myeloma were chosen for such a clinical trial because there is no curative therapy for this cancer today-only life-extending treatment.
In the other known clinical studies with AbM, the mushroom was reported to have positive effect against nonlymphocytic leukemia [ 42 ] and to increase quality of life and NK-cell activity in blood of gynaecological cancer patients on high-dose chemotherapy [ 31 ].
In a small AbM study on prostate cancer in patients enrolled after radical prostatectomy, there was no reduction in their prostate-specific antigen PSA levels [ 58 ]. However, there were no placebo controls, and the study included many with PSA values below the guideline of 0. That study is in contrast with the findings of AbM-induced apoptosis for prostate cancer cells and inhibited tumor growth and antiangiogenic effect in a mouse model [ 44 ].
Interestingly, a recent paper reported evidence for suppressed growth and invasiveness of human breast cancer cells in vitro after treatment with a blend of AbM and other medicinal mushrooms [ 59 ].
Table 1 gives an overview over the reported in vivo antitumor effects of the Agaricus bM mushroom, and Table 2 shows clinical studies with this mushroom. Thus, AbM ameliorates the Th2-skewed balance found in advanced cancer, mycobacterial infections and allergy and asthma. Hence, AbM extract may show promise as a prophylacticum and as an additive treatment for quite different and some serious diseases. Lyberg and G. Kvalheim have no relationships to declare. Hetland and E. Johnson are option and stock holders in ImmunoPharma AS.
National Center for Biotechnology Information , U. Journal List Adv Pharmacol Sci v. Adv Pharmacol Sci. Published online Sep 6. Author information Article notes Copyright and License information Disclaimer. Received Mar 11; Accepted Jun This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. This article has been cited by other articles in PMC.
Abstract The medicinal mushroom Agaricus blazei Murill from the Brazilian rain forest has been used in traditional medicine and as health food for the prevention of a range of diseases, including infection, allergy, and cancer. Open in a separate window. Figure 1. Figure 2. Figure 3. Anti-Inflammatory Effect In a human phase I study in 15 healthy volunteers, we recently found no side effects after intake of the AbM-based AndoSan extract [ 23 , 24 ].
Figure 4. Mechanism: Stimulation of Immune Cells The reason for the forceful and swift engagement of innate immunity when encountering an edible and harmless mushroom, such as AbM, is its sharing of pathogen-associated molecular patterns PAMP with other highly poisonous species.
Figure 5. Figure 6. Antitumor Effects and Proposed Mechanism behind As mentioned, the Agaricus mushroom is reported to inhibit various tumors [ 10 ], including hematological cancers such as myeloma in a recent mouse model [ 43 ] and leukemia in a human study [ 42 ]. Table 1 Reported in vivo antitumor effect of the mushroom Agaricus blazei Murill. Patients disease No.
5 Things You Should Know Before You Buy Agaricus blazei Mushroom Extract
Agaricus blazei Murill mushroom extract is a natural health supplement that is becoming extremely popular in Japan. Supplement and pharmaceutical manufacturers often use the fruit body or mycelium of the Agaricus blazei mushroom to produce the extract. The fruit body is the portion of the fungus that is above ground, and the mycelium is the part of the fungus that resides underground. The nutritional profiles of the fruit body and mycelium are slightly different.
The Health Benefits of Agaricus Blazei Mushroom
Agaricus blazei Murill ABM has shown particularly strong results in treating and preventing cancer and has also traditionally been used as a food source in Brazil. However, the exact immune responses regarding the phagocytosis of macrophage and, the activity of natural killer NK cells in normal mice after exposure to ABM extract was unclear. The results indicated that ABM extract significantly promoted the proliferation of splenocytes both in vitro and in vivo. The percentage of macrophages with phagocytosis after ABM extract treatment increased and these effects were of dose-dependent manners, both in vitro and in vivo.
Metrics details. Agaricus blazei Murill AbM is an edible Brazilian mushroom that has been used in traditional medicine for a range of diseases. It has been shown to have anti-infection and anti-tumor properties in the mouse, which are due to induction of Th1 responses. On the other hand, IgE-mediated allergy is induced by a Th2 response.