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      The Medicinal Mushroom Agaricus blazei Murrill: Review of Literature and Pharmaco-Toxicological Problems

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          Abstract

          Agaricus blazei Murrill (ABM) popularly known as ‘ Cogumelo do Sol’ in Brazil, or ‘ Himematsutake’ in Japan, is a mushroom native to Brazil, and widely cultivated in Japan for its medicinal uses, so it is now considered as one of the most important edible and culinary-medicinal biotechnological species. It was traditionally used to treat many common diseases like atherosclerosis, hepatitis, hyperlipidemia, diabetes, dermatitis and cancer. In vitro and in vivo ABM has shown immunomodulatory and antimutagenic properties, although the biological pathways and chemical substances involved in its pharmacological activities are still not clear. The polysaccharides phytocomplex is thought to be responsible for its immunostimulant and antitumor properties, probably through an opsonizing biochemical pathway. Clinical studies are positive confirmations, but we are still at the beginning, and there are perplexing concerns especially relative to the content of agaritine. Argantine is a well-known carcinogenic and toxic substance in animals, that must be completely and fully evaluated.

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          Most cited references106

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          Immune recognition. A new receptor for beta-glucans.

          The carbohydrate polymers known as beta-1,3-d-glucans exert potent effects on the immune system - stimulating antitumour and antimicrobial activity, for example - by binding to receptors on macrophages and other white blood cells and activating them. Although beta-glucans are known to bind to receptors, such as complement receptor 3 (ref. 1), there is evidence that another beta-glucan receptor is present on macrophages. Here we identify this unknown receptor as dectin-1 (ref. 2), a finding that provides new insights into the innate immune recognition of beta-glucans.
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            Mechanism by which orally administered beta-1,3-glucans enhance the tumoricidal activity of antitumor monoclonal antibodies in murine tumor models.

            Antitumor mAb bind to tumors and activate complement, coating tumors with iC3b. Intravenously administered yeast beta-1,3;1,6-glucan functions as an adjuvant for antitumor mAb by priming the inactivated C3b (iC3b) receptors (CR3; CD11b/CD18) of circulating granulocytes, enabling CR3 to trigger cytotoxicity of iC3b-coated tumors. Recent data indicated that barley beta-1,3;1,4-glucan given orally similarly potentiated the activity of antitumor mAb, leading to enhanced tumor regression and survival. This investigation showed that orally administered yeast beta-1,3;1,6-glucan functioned similarly to barley beta-1,3;1,4-glucan with antitumor mAb. With both oral beta-1,3-glucans, a requirement for iC3b on tumors and CR3 on granulocytes was confirmed by demonstrating therapeutic failures in mice deficient in C3 or CR3. Barley and yeast beta-1,3-glucan were labeled with fluorescein to track their oral uptake and processing in vivo. Orally administered beta-1,3-glucans were taken up by macrophages that transported them to spleen, lymph nodes, and bone marrow. Within the bone marrow, the macrophages degraded the large beta-1,3-glucans into smaller soluble beta-1,3-glucan fragments that were taken up by the CR3 of marginated granulocytes. These granulocytes with CR3-bound beta-1,3-glucan-fluorescein were shown to kill iC3b-opsonized tumor cells following their recruitment to a site of complement activation resembling a tumor coated with mAb.
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              Soluble beta-glucan polysaccharide binding to the lectin site of neutrophil or natural killer cell complement receptor type 3 (CD11b/CD18) generates a primed state of the receptor capable of mediating cytotoxicity of iC3b-opsonized target cells.

              When phagocyte CR3 binds to iC3b on bacteria or yeast, phagocytosis and degranulation are triggered because of simultaneous recognition of iC3b via a CD11b I-domain binding site and specific microbial polysaccharides via a lectin site located COOH-terminal to the I-domain. By contrast, when phagocyte or natural killer (NK) cell CR3 adheres to iC3b on erythrocytes or tumor cells that lack CR3-binding membrane polysaccharides, neither lysis nor cytotoxicity are stimulated. This investigation showed that soluble CR3-specific polysaccharides such as beta-glucan induced a primed state of CR3 that could trigger killing of iC3b-target cells that were otherwise resistant to cytotoxicity. Anti-CR3 added before sugars prevented priming, whereas anti-CR3 added after sugars blocked primed CR3 attachment to iC3b-targets. Polysaccharide priming required tyrosine kinase(s) and a magnesium-dependent conformational change of the I-domain that exposed the CBRM1/5 activation epitope. Unlike LPS or cytokines, polysaccharides did not up-regulate neutrophil CR3 expression nor expose the mAb 24 reporter epitope representing the high affinity ICAM-1-binding state. The current data apparently explain the mechanism of tumoricidal beta-glucans used for immunotherapy. These polysaccharides function through binding to phagocyte or NK cell CR3, priming the receptor for cytotoxicity of neoplastic tissues that are frequently targeted with iC3b and sparing normal tissues that lack iC3b.
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                Author and article information

                Journal
                Evid Based Complement Alternat Med
                ecam
                ecam
                Evidence-based Complementary and Alternative Medicine : eCAM
                Oxford University Press
                1741-427X
                1741-4288
                March 2008
                27 March 2007
                : 5
                : 1
                : 3-15
                Affiliations
                1Center of Natural Medicine and 2Department of Internal Medicine, S. Giuseppe Hospital, Az USL 11, Empoli, Italy
                Author notes
                For reprints and all correspondence: Dr Fabio Firenzuoli, Center of Natural Medicine, S. Giuseppe Hospital, via Paladini 40, 50053 Empoli, Italy. Tel: +39-0571-702661; Fax: +39-0571-702639; E-mail: f.firenzuoli@ 123456usl11.toscana.it
                Article
                nem007
                10.1093/ecam/nem007
                2249742
                18317543
                f4f436c6-9449-4bb3-8e39-812a18590ead
                © 2007 The Author(s).

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 7 July 2006
                : 10 January 2007
                Categories
                Reviews

                Complementary & Alternative medicine
                agartine,agaricus blazei murrill (abm),immune response,cancer prevention,medicinal mushroom

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