INTRODUCTION:
The Shiitake (Lentinula edodes) is an edible medicinal mushroom, so well known in the East; it’s much sought after for its therapeutic effects and for strengthen the immune system.
This mushroom is widespread above all in Japan and China, where is part of the common alimentation. The name Shiitake, derive from the japanase term “shii” that suggest oak, the tree where it especially grow up; and the term “take” that means mushroom. [1]
PROPERTIES:
Many studies validate the role of Shiitake in various pathology, like cardiovascular disease and cancer. In particular, this mushroom have immunostimolatory and immunomodulatory properties: its components act balancing and strengthening the body's immune system. From shiitake was isolated lentinan, a beta-glucan (carbohydrate of high molecular weight, composed by the aggregation of simple sugars), that is able to solicit macrophages, lymphocytes T and Natural Killer cells, or those types of white blood cells deputies to recognize and destroy potentially harmful elements in the body.
This process, connected to an increased production of antibodies, acts as a barrier against both bacterial and viral infections and helps to inhibit cancerous cells proliferations in certain malignancies.
The property of Shiitake are also reducing cholesterol and prevent atherosclerosis; it exerts a protective action on the liver and promotes the formation of antibodies against HBV; it fights some fungal infections such as those caused by Candida Albicans; it has prebiotic effect as in the intestine it promotes the formation of "good" bacterial flora; it combats tooth decay, due to the germicidal power versus Streptococcical’s species that lurk in the dental plaque; finally it helps in physical and mental exertion’s situations.
Research on shiitake documented that the active shiitake, improving the immune response, may be a natural complement to traditional therapies against cancer. In particular, a study of 2002 shows how the lentinan facilitates the regression of colon cancer . Experiments even more recent (2009) connect its administration to an increased survival of patients with gastric cancer and pancreatic cancer in advanced stage. It 'also appreciated the concomitant reduction of side effects of chemotherapy treatments. [2;3]
NUTRITIONAL ROLE:
The shiitake is also interesting from a nutritional point of view: it has essential amino acids, minerals (potassium, calcium, magnesium, manganese, iron, copper and zinc), vitamins B and ergosterol, a precursor of vitamin D. Lentinula edodes has a taste that remembers meat and that makes it suitable to accompany many foods.
The most practical and usefulness way of assumption, however, is represented by the capsules, some extracts, the entire mushroom or its parts. The dosage of shiitake is usually 1-2 capsules per day, even for a few months (eg, such as prevention of flu and other winter illnesses). The use of shiitake as a supplement at recommended doses in micoterapia, is safe, well tolerated and compatible with other treatments. Only massive and prolonged consumption of the fungus, in rare cases, can lead to side effects such as phenomena of photosensitive dermatitis and gastrointestinal disorders.
CONTROINDICATIONS:
Shiitake’s contraindications concern individuals allergic to mushrooms and those who have undergone an organ transplant. [4]
SHIITAKE and IMMUNOLOGICAL EFFECTS:
It has been reported that β-glucans with a higher degree of structural complexity, such as those that are triple helixes or particulate, are associated with potent immunopotentiating, antifungal and anticancer effects. Despite their high-molecular weight, β-glucans can be absorbed via M cells of the intestinal membrane and are detected by macrophages or DCs residing in Peyer’s patches. β-Glucans play a crucial role in activating the host immune response against fungal invasion.
An important role in the response to the immune system, is given by dectin-1 and complement receptor 3 (CR3), that are responsible for binding to β-glucans, allowing the immune cells to recognize them as "non-self". Dectin-1 may play a role in acquired immunity by rapid antigen presentation through enhanced phagocytosis and ROS production.
In the absence of its receptor dectin-1, β-glucan may not initiate an anti-fungal defense in host as an antigen for an acquired immune response. Indeed, in most cases, the level of defense is minimal without assistance from dectin-1. The importance of dectin-1 is dramatically demonstrated in the case of the dectin-1 Y238X mutation, in which CRD is not functional. In heterozygous carriers of this mutation, antifungal immunity is incomplete, and the level of immunity is not low enough to threaten normal life. However, homozygotes of this mutation are greatly affected and always experience a severe infection especially of the mucocutaneous membranes. Still, the dectin-1 free anti-fungal defense might function effectively and, theoretically, acquired immunity against β-glucan might be enhanced by consistent use of β-glucan. Significant cooperation exists between dectin-1 and other receptors against fungal polysaccharides. Future studies are needed to probe the interactions among these receptors. Needless to say, further elucidation of dectin-1 function and its potential ligands will aid in the development of biomolecules and therapeutics to reinforce the remedy of β-glucan against anti-fungal agents.
In addition to the pathways, signals from dectin-1 may follow another Syk independent route. Dectin-1 could trigger a Raf1-mediated pathway that modulates NF-κB activation .In this case, Raf-1 binds to the cytoplasmic domain of dectin-1 and increases p60 phosphorylation independent of Syk, which also occurs in the Syk-dependent pathway. This pathway exerts a synergistic effect along with β-glucan signaling. In addition, this pathway may serve as an alternative signal transduction pathway when the Syk-dependent pathway is blocked.
A recent discovery, is dectin-2 receptor, that recognizes high mannose and α-mannan structures. Mannan is a polymer of mannose that is usually found in yeast, bacteria and plants. α-Mannan is mainly found in yeast cell walls, while β-forms are found in the cell walls of higher plants. In contrast to dectin-1, dectin-2 lacks an ITAM motif in the cytoplasmic domain. Dectin-2 consequently employs the Fc receptor γ recep (FcRγ), which contains an ITAM motif . When FcRγ associates with dectin-2, Syk is recruited to the ITAM domain. The rest of the dectin-1 and dectin-2 signal transduction pathways are believed to be identical. [5]
Moreover, the methanolic extract of the fruit bodies of L. edodes was investigated for cytoprotective effect against H2O2-induced cytotoxicity in human peripheral blood mononuclear cells (PBMCs) by measuring the activities of xanthine oxidase (XO) and glutathione peroxidase (GPx) .
This suggested that one of the possible mechanisms via which L. edodes methanolic extract confers protection against H2O2-induced oxidative stress in PBMC, is by inhibiting the superoxide-producing of xanthine oxidase and increasing glutathione peroxidase activity which could rapidly inactivate H2O2. [6]
Recognition of B-glucans on fungal particles induces several dectin-1-mediated cellular responses, which might contribute to anti-fungal immunity in vivo. These include fungal uptake and killing and the production of pro-inflammatory cytokines and chemokines, such as tumour-necrosis factor (TNF) and CXC-chemokine ligand 2 (CXCL2), in collaboration with the Toll-like receptors (TLRs)11, 19, which is likely to lead to cellular recruitment and activation. Dectin-1-mediated recognition also stimulates the production of interleukin-12 (IL-12), which might result in a protective T-helper 1 (TH1)-cell response and the production of interferon-y (IFN- y), thereby activating the fungicidal activities of phagocytes. In dendritic cells, B -glucan recognition by dectin-1 can also induce the production of IL-10 and IL-2, which could potentially contribute to the development of regulatory T cells, thereby limiting inflammatory pathology and promoting fungal persistence and long-term immunity, as proposed previously. IL-10 would also inhibit the production of pro-inflammatory cytokines and chemokines. Fungi might also mask their B-glucan, by conversion from yeast to hyphal forms70. This could result in the induction of non-protective TH2-cell immune responses, mediated by IL-4; this could be the result of preventing recognition by dectin-1 although the pathways leading to this response are unknown. Although dectin-1 is described here as having a central role in the generation of protective immune responses, it should be noted that many other opsonic and non-opsonic receptors (such as the mannose receptor, complement receptor 3 (CR3), dendritic-cell-specific ICAM3-grabbing non-integrin (DC-SIGN) and TLRs also contribute to this process.
SHIITAKE and CANCER PROTECTION:
The action of Lentinan is manifested in vivo, by stimulating the immune system it destroyes the tumoral cells by activating macrophages, NK, LT and citokyne’s production. Japanese’ doctors usually prescribe Shiitake for his efficacy in extending the life’s expectation in many types of cancer, in particular gastric, colon and rectal type.
In fact, Lentinan (LNT) is an immune adjuvant medicine for advanced gastric cancer in Japan. Recently, an oral formulation of superfine dispersed lentinan (SDL) has become clinically available.
Studies demonstrate that SDL is safe and effective for suppressing the adverse effects of chemotherapy as well as improving quality of life. The binding ability of peripheral blood monocyte to LNT appears to be a promising predictor of quality of life improvement after SDL administration.
Lentinan (LNT) is a purified β-1,3-glucan with β-1,6-branches derived from the edible mushroom Lentinus edodes. LNT has immune adjuvant effects and has been reported to increase host defense mechanisms against murine and human tumors. The clinical efficacy of LNT, such as its effect on long-term survival and the improvement of the quality of life (QOL) status, were evaluated in patients with inoperable and recurrent gastric cancer. The mode of action of LNT consists of T-cell dependent immunopotentiation mediated by macrophages and monocytes. Studies of some β-glucan receptors such as CD11b, dectin-1 and toll-like receptor 2 (TLR2) have revealed that β-glucan binds to these receptors on macrophages and monocytes. Furthermore, LNT-induced reductive macrophages are reportedly skewed toward Th1 as a result of the production of IL-12, and the binding ability of peripheral blood monocytes (PBM) to LNT might directly influence its in vivo effects . Intravenously administered LNT can cancel a Th2-dominant condition in patients with digestive tract cancer and improve the balance between Th1 and Th2 . However, why orally administered LNT is ineffective has been a long-standing puzzle. In aqueous solution, the particle size of LNT is approximately 100 to 200 μm; this impedes the absorption of LNT particles through the intestinal mucosa. Recently, an oral formulation of superfine dispersed lentinan (SDL) has been developed and is now clinically available. SDL reportedly enables the potentiation of intestinal mucosal immunity .
Moreover LNT increases the intracellular reductive glutathione content as well as the N-acetylcysteine content and scavenges ROS by increasing reductive glutathione. Thus, the oral administration of SDL may be useful for the suppression of chemotherapy toxicity. [7;8;9]
BIBLIOGRAPHY:
[1] Wikipedia
[2] Lentinula edodes (Shiitake) mushroom extract protects against hydrogen peroxide induced cytotoxicity in peripheral blood mononuclear cells.
Kuppusamy UR1, Chong YL, Mahmood AA, Indran M, Abdullah N, Vikineswary S.
[3] Inhibition of human colon carcinoma development by lentinan from shiitake mushrooms (Lentinus edodes).
Ng ML1, Yap AT.
[4] http://www.ncbi.nlm.nih.gov/pubmed/?term=property+of+shitake
[5] Immunomodulation of Fungal β-Glucan in Host Defense Signaling by Dectin-1
Sainkhuu Batbayar, Dong Hee Lee,* and Ha Won Kim*
[6]Lentinula edodes (Shiitake) mushroom extract protects against hydrogen peroxide induced cytotoxicity in peripheral blood mononuclear cells.
Kuppusamy UR1, Chong YL, Mahmood AA, Indran M, Abdullah N, Vikineswary S
[7] Efficacy of oral administered superfine dispersed lentinan for advanced pancreatic cancer.
Shimizu K1, Watanabe S, Watanabe S, Matsuda K, Suga T, Nakazawa S, Shiratori K.
[8] Efficacy of orally administered superfine dispersed lentinan (beta-1,3-glucan) for the treatment of advanced colorectal cancer.
Hazama S1, Watanabe S, Ohashi M, Yagi M, Suzuki M, Matsuda K, Yamamoto T, Suga Y, Suga T, Nakazawa S, Oka M.
[9] Efficacy of Orally Administered Superfine Dispersed Lentinan (β-1,3-Glucan) for the Treatment of Advanced Colorectal Cancer
SHOICHI HAZAMA, SEIJI WATANABE, MANABU OHASHI, MASASHI YAGI, MICHINARI SUZUKI, KENJI MATSUDA, TATSUHITO YAMAMOTO, YASUYO SUGA, TETSUYA SUGA,SABURO NAKAZAWA10 and MASAAKI OKA1
