Journal of Clinical Biochemistry and Nutrition
Online ISSN : 1880-5086
Print ISSN : 0912-0009
ISSN-L : 0912-0009
Serial Review
Immunomodulating compounds in Basidiomycetes
Masashi MizunoYosuke Nishitani
著者情報
ジャーナル フリー HTML

2013 年 52 巻 3 号 p. 202-207

詳細
Abstract

Mushrooms are distinguished as important food containing immunomodulating and anticancer agents. These compounds belong mostly to polysaccharides especially β-d-glucans. Among them, β-1,3-glucan with side chain β-1,6-glucose residues have more important roles in immunomodulating and antitumor activities. In this review, we have introduced polysaccharide mainly from Lentinula edodes and Agaricus blazei Murill with immunomodulating and antitumor activities. In addition, the mechanism of activation of immune response and signal cascade are also reviewed.

Introduction

Fungi are classified in the independent kingdom Fungi among other organisms. Fungi kingdom contains five main phyla including Ascomycota, Basidiomycota, Chytridiomycota, Glomeromycota and Zygomycota. Nowadays fungi are distinguished as important natural resources of immunomodulating and anticancer agents. With regard to the increase in diseases involving immune dysfunction, cancer, autoimmune conditions in recent years, application of such immunomodulator agents especially one with a natural original is vital. Generally, fungi are referred as ”mushrooms” which are popular term for their fruiting bodies. Most mushrooms are commonly found in the shape of umbrella with pileus (Cap) and stipe (Stem) as shown in Fig. 1. Pileus is conical, flat or even spherical. Sporophore usually present on the lower surface of pileus and composed of many thin layers stacked side by side. Some mushrooms also have pores.

Fig. 1

Main mycological name of typical mushroom.

In the 21st century, mushrooms have attracted attention as natural resources due to their low toxicity and high specificity to activate immune system in our body. The number of the mushrooms on Earth is estimated at 140,000. However, probably only around 10% of them are taxonomically known. Assuming that proportion of useful mushrooms among undiscovered and unexamined mushrooms is only 5%, this implies that 7,000 yet undiscovered species will be of possible benefit to mankind.(1) Mushrooms such as Lentinula edodes, Ganoderma lucidum, Schizophillum commune, Sclerotinia selerotiorum, Fomes fomentarius and many others have particularly been used as a traditional medicine to remedy different diseases for centuries in Japan, China and Korea.(2) One of the first studies pertaining to the antitumor properties of Basidiomycetes mushrooms was carried out by Lucas and coworkers, who successfully applied an extract obtained from Boletus edulis fruiting bodies in the treatment of Sarcoma 180 in mice.(3) Its effect was confirmed against many experimental tumors, including Sarcoma 180, mammary adenocarcinoma 755, leukemia L-1210 and Hela cell lines.(4) Since then, the hot water extracts of these mushrooms have been widely used for treatment purpose in many Eastern countries. The most active constituents in these extracts are polysaccharides, which have been found to boost the human immune system, showing anti-cancer and anti-viral activities. Numerous studies have shown that the antitumor properties of biologically active compounds isolated from mushrooms are mostly attributed to polysaccharides.(47) Their main source appears to be fungal cell walls. The most important polysaccharides from mushrooms were summarized in Table 1. It was made clear that most polysaccharides composed of β-d-glucan moiety as a main chain.

Table 1 Polysaccharides isolated from mushrooms possessing some immunomodulating and antitumor activity
Mushroom Polysaccharide structure Reference
Lentinula edodes (1→3)-β-d-glucan with (1→6)-β-d side chain (8)
Agaricus blazei (1→3)-β-d-glucan, heteropolysaccharides, polysaccharide-protein complex (9)
Grifola frondosa (1→6)-β-d-glucan with (1→3)-β-d side chain (10)
Ganoderma lucidum β-d-glucans, heteropolysaccharides, glycoproteins (11)
Flammulina velutipes Protein (12)
Hericium erinaceum Galactoxyloglucan-protein complex (13)
Schizophillum commune (1→3)-β-d-glucan with (1→6)-β-d-glucosyl branches (14)

Evidences accumulated that the food factors influence the function of our immune system. Therefore, alternation of dietary components received a lot of attention as a tool which can improve our immune system. β-Glucans, which is one of the most attractive food factors possessing immunomodulating activities without adverse effect, are currently under investigation for this purpose. This review article concentrates on Basidiomycetes-derived polysaccharides that possessed immunomodulating activities.

Lentinula edodes

Lentinula edodes, the Shiitake mushroom, is one of the many very popular edible mushrooms in Japan. This mushroom is known as functional food. Lentinan, an antitumor polysaccharide, was isolated and purified from a hot water extract of Lentinula edodes fruit bodies.(14) The structure of lentinan was reported as a (1→3)-β-d-glucan having two (1→6)-β-glucopyranoside branches for every five (1→3)-β-glucopyranoside linear linkages (Fig. 2).(1417) Lentinan is also known as a type of biological response modifier.(18) Since lentinan did not show any direct cytotoxicity against tumor cells, its antitumor action is considered host-mediated.(19) It is thought that lentinan augments the immune response through modulating phagocytes such as macrophages.(20,21) It has been reported that lentinan possesses immunomodulating effect as it seems to activate variety of macrophage functions, e.g. some cytokines and superoxide anion production, phagocytosis, and cytotoxicity.(2225) Moreover, it has been reported that macrophages secreted tumor necrosis factor-α (TNF-α) through the stimulation by lentinan.(26) TNF-α is recognized as the primary cytokine produced mainly by activated macrophages; it is an important host defense molecule that affects tumor cells.(27) Hoffman et al.(28) observed that TNF-α was released from macrophages through a β-glucan mediated mechanism. Lentinan increases peritoneal macrophage cytotoxicity against metastatic tumors. It can initiate normal and alternative pathways of the complement system, splitting C3 into C3a and C3b, thereby enhancing macrophage activation.(2) Recently, Xu et al.(29) investigated the effects of lentinan on the nitric oxide (NO) and TNF-α production in lipopolysaccharide (LPS)-stimulated murine RAW 264.7 macrophages. It was demonstrated that treatment with lentinan not only resulted in the striking inhibition of TNF-α and NO production in LPS-activated macrophage RAW 264.7 cells, but also the protein expression of inducible nitric oxide synthase (iNOS) and the gene expression of iNOS mRNA and TNF-α mRNA. Thus, there are many studies for the fascinating effects of lentinan on the responsiveness or function of the immune cells involved.

Fig. 2

Structure units of lentinan.

Recently, Mizuno et al.(30) have reported that lentinan exhibits the immune suppressive effects such as intestinal anti-inflammatory properties using co-culture system composed of Caco-2 cells and RAW264.7 cells. When RAW264.7 cells were stimulated with LPS, interleukin (IL)-8 and TNF-α secretion increased. In this system, lentinan treatment on the apical side inhibited only IL-8 mRNA expression and its secretion without affecting TNF-α production from RAW264.7. Moreover, they demonstrated that lentinan exhibited different suppressive effects from fucoidan on IL-8 mRNA expression in Caco-2 through TNF-α production from RAW264.7 stimulated with LPS. As it has been reported that β-glucan is recognized through the dectin-1 receptor in intestinal epithelial cells,(31) they speculated that the difference in receptors between lentinan and fucoidan which is a polymer of L-fucose linked by an α-1,2-linkage with a sulfate group mainly at the O-4 position (32) was due to the different suppressive effects on IL-8 mRNA expression in Caco-2.

The immunomodulating effects and/or indirect antitumor activity of lentinan are attributed to the activation of immune effector cells such as hematopoietic stem cells, lymphocytes, macrophages, T cells, dendritic cells, and natural killer cells involved in the innate and adaptive immunity. Lentinan can affect these cells via modulating cytokines secretion such as TNF-α which function as cell signal messenger. Humans and mice studies revealed that immune cells stimulated with lentinan increased cytokine production.(33,34) It was also reported that lentinan can enhance the production of chemical messenger such as nitric oxide through TNF-α production.(35) Immunomodulating activity of lentinan may be linked to its hormonal modulating factors which can play a role in tumor growth. Aoki(36) showed that the antitumor activity of lentinan is strongly reduced by administration of thyroxin or hydrocortisone. Lentinan can also restore tumor specific antigen-directed delayed type hypersensitivity reaction. The mechanism of anti-tumor activity of lentinan is summarized in Fig. 3.(37)

Fig. 3

Mechanism of antitumor activity of lentinan.

Agaricus blazei Murill

Agaricus blazei Murill is one of the most intensively studied medicinal mushrooms(9,38,39) among others that used to treat many diseases.(4044) It was reported that the extract of Agaricus blazei Murill has potent antitumor activity in mice, postulated to be exerted through mediation of the host immune system by β-(1→6)- and β-(1→3)-glucan.(9,4548) These functions of Agaricus blazei Murill have been shown to indirectly affect the immune system.

Not only fruit bodies but cultured mycelia of Agaricus blazei Murill are also a source of antitumor polysaccharides. An antitumor organic substance ”ATOM” was representative of Agaricus blazei Murill.(39) ATOM was highly effective on subcutaneously implanted Sarcoma 180 in mice, and was also activated against Ehrlich ascites carcinoma, Shionogi carcinoma 42 and Meth A fibrosarcoma. Mizuno et al.(49) has separated a new antitumor polysaccharide, β-(1→2)-;β-(1→3)-glucomannan, which acted against Sarcoma 180 from liquid cultured mycelium of Agaricus blazei Murill. It was reported that a similar polysaccharide was also obtained from submerged culture mycelium, in which the main component is glucose and mannose.

As mentioned above, antitumor polysaccharides researched in Agaricus blazei Murill fruit body, culture mycelia, or extracellularly produced in culture medium have a number of different chemical structures. Polysaccharides from fruit bodies possessed glucans with different types of glucose unit connections or heteroglucans. In contrast, culture mycelia contained glucomannan and mannan-protein complex was produced in a culture medium under submerged cultivation.

Recently, it was reported that oral administration of Agaricus blazei Murill possessed anti-allergic activity alleviating the severity of dermatitis and levels of serum immunoglobulin E (IgE) in NC/Nga mice, which developed atopic dermatitis-like skin lesions induced by repeated challenge with picryl chloride.(50) It was demonstrated that Agaricus blazei Murill increased interferon (IFN)-γ contents in serum. IFN-γ is a strong inhibitor of IgE synthesis and Th2 cell proliferation, as well as inducing differentiation from Th0 to Th1 cells. Moreover, Agaricus blazei Murill upregulated IFN-γ production and inhibited IL-4 secretion in spleen cells. These results suggested that Agaricus blazei Murill established Th1 dominance, which contributes to cellular immunity. Choi et al.(51) demonstrated that the water extract of Agaricus blazei Murill fruiting body suppressed allergic edema after oral administration and reduced histamine release by direct incubation with mast cells. Bouike et al.(52) described that Agaricus blazei Murill suppressed IgE content in OVA-sensitized mice due to the activation of macrophages via intestinal epithelial cells (IEC) and subsequently promoted differentiation of naïve T cells into Th1 cells in the immune system. Also, they proposed the involvement of H2O2 as a second messenger in the cross talk between IEC and antigen presenting cells such as macrophages and dendritic cells (Fig. 4).

Fig. 4

Mechanism of Shift in Th1/Th2 balance to Th1 by Agaricus blazei Murill extract through intestinal epithelial cells. TNF-α, tumor necrosis factor-α; IFN-γ, interferon-γ; IL-4, -5 and -10, interleukin-4, -5, 10.

Other Mushrooms

A wide range of antitumor or immunomodulating polysaccharides of different chemical structure from Basidiomycetes mushrooms has been investigated with the exception of Lentinula edodes and Agaricus blazei Murill. The main varieties were listed in Table 2. Grifola frondosa is also one of the most popular medicinal mushrooms in Japan. This mushroom consisted mainly of β-(1→6)-;β-(1→3)-glucan(10) and β-(1→3);β-(1→6)-glucan(53) as a water-soluble polysaccharide fractions which are antitumor polysaachrides. This fractions also included an acidic xyloglucan and three acidic glucoproteins with molecular weight of 20–100 kDa. Polysaccharides in Grifola frondosa composed of β-glucan with different side chain components. Ganoderma Tsugae is another medicinal mushroom of which polysaccharides have been investigated for antitumor activities. Water-soluble fractions contained 7 glycans with strong antitumor properties which were protein-glucogalactans complex with mannose and fucose residues.(54) As another edible mushroom, Mizuno et al.(55) reported that polysaccharide in Sarcodon aspratus showed the highest mitogenic activity among the eight mushrooms tested. Fucogalactan was identified as an active compound in Sarcodon aspratus. Moreover, this polysaccharide elicited the release of TNF-α from macrophage cell line RAW264.7 and its activity is higher than lentinan by approximately 4 fold. Thus, a number of different polysaccharides derived from Basidiomycetes exhibited antitumor and immunomodulating activities.

Table 2 Polysaccharides of higher Basidiomycetes possessing antitumor or immunomodulating activities
Species Polysaccharides
Agaricus blazei α-(1→4)-;β-(1→6)-glucan
α-(1→6)-;α-(1→4)-glucan
β-(1→6)-;β-(1→3)-glucan
β-(1→6)-;α-(1→3)-glucan
Mannogalactoglucan
Riboglucan
β-(1→2)-;β-(1→3)-glucomannan
Glucomannan
Agrocybe aegerita Linear α-(1→3)-glucan
Amanita muscaria Linear α-(1→3)-glucan
Armiariella tabescens α-(1→3)-glucan
β-(1→6)-glucan
Dictyophora indusiata α-(1→3)-mannan
Fucomannogalactan
Flammulina velutipes Galactomannoglucan
Fomitella fraxinea α-(1→6)-mannofucogalactan
Gahoderma tsugae Arabinoglucan
Ganoderma lucidum β-(1→3)-glucuronoglucan
Mannogalactoglucan
Ganoderma tsugae Glucogalactan
Grifola frondosa β-(1→6)-;β-(1→3)-glucan
Xyloglucan
Mannogalactofucan
Mannoxyloglucan
Hericium erinaceus Xylan
Glucoxylan
Mannoglucoxylan
Galactoxyloglucan
Hohenbuehelia serotina Galactomannoglucan
Inonotus obliquus Xylogalactoglucan
Lentinula edodes β-(1→3)-;β-(1→6)-glucan
Galactoglucomannan
Leucopaxillus giganteus Galactomannoglucan
Lyophyllum decastes β-(1→6)-glucan
Pleurotus citrinopileatus Arabinogalactan
Pleurotus cornucopiae Mannogalactoglucan
Pleurotus pulmonarius Xyloglucan
Mannogalactoglucan
Mannogalactan
Glucoxylan
Polyporus confluens Xyloglucan
Sarcodon aspratus Fucogalactan

Conclusion

Mushrooms have been part of a diet for over 2,000 years. Traditional practices and scientific research have focused on mushrooms as a group of highly recommended dietary supplement and medicine due to their evidently nutritional values. Many mushrooms, if not all Basidiomycetes contain biologically and physiologically active polysaccharides. These polysaccharides are different in chemical structures but are consisted chiefly of β-glucans. It is evidently that structural features such as β-(1→3) linkages in the main chain of the glucan and additional β-(1→6) branch portion are necessary for antitumor and immunomodulatory action. The antitumor activities of the polysaccharides from mushrooms have been proven to act by affecting different immune response in the host such as our body. A number of studies have proposed several antitumor mechanisms. However, it is widely expected that a more scientific approach is required to build up the theories. Scientific assessment of compounds contained in mushrooms will redound the prevention and treatment of lifestyle diseases including cancer.

Abbreviations

IEC; intestinal epithelial cells, IFN-γ; interferon-γ, IgE; immunoglobulin E, IL-8; interleukin-8, iNOS; inducible nitric oxide synthase, LPS; lipopolysaccharide, NO; nitric oxide, TNF-α; tumor necrosis factor-α

Conflict of Interest

No potential conflict of interests were disclosed.

References
  • 1   Hawksworth  DL. Mushrooms: the extent of the unexplored potential. Int J Med Mushrooms 2001; 3: 333–337.
  • 2   Wasser  SP. Medicinal mushrooms as a source of antitumor and immunomodulating polysaccharides. Appl Microbiol Biotechnol 2002; 60: 258–274.
  • 3   Lucas  EH,  Montesano  R,  Pepper  MS,  Hafner  M,  Sablon  E. Tumor inhibitors in Boletus edulis and other holobasidiomycetes. Antibiot Chemother 1957; 7: 1–4.
  • 4   Wasser  SP,  Weis  AL. Medicinal properties of substances occurring in higher Basidiomycetes mushrooms: current perspectives. Int J Med Mushrooms 1999; 1: 31–62.
  • 5   Mizuno  T. The extraction and development of antitumor-active polysaccharides from medicinal mushrooms in Japan. Int J Med Mushrooms 1999; 1: 9–29.
  • 6   Mizuno  T. Bioactive substances in Hericium erinaceus (Bull. Fr.) Pers. (Yamabushitake), and its medicinal utilization. Int J Med Mushrooms 1999; 1: 105–119.
  • 7   Reshetnikov  SV,  Wasser  SP,  Tan  KK. Higher Basidiomycota as a source of antitumor and immunostimulating polysaccharides. Int J Med Mushrooms 2001; 3: 361–394.
  • 8   Chihara  G,  Maeda  Y,  Hamuro  J,  Sasaki  T,  Fukuoka  E. Inhibition of mouse sarcoma 180 by polysaccharides from Letinus edodes (Berk.) sing. Nature 1969; 222: 687–688.
  • 9   Mizuno  T,  Inagaki  R,  Kanao  T, et al. Antitumor activity and some properties of water-insoluble hetero-glycans from ”Himematsutake,” the fruiting body of Agaricus blazei Murill. Agric Biol Chem 1990; 54: 2897–2905.
  • 10   Nanba  H,  Hamaguchi  A,  Kuroda  H. The chemical structure of an antitumor polysaccharide in fruit bodies of Grifola frondosa (Maitake). Chem Pharm Bull (Tokyo) 1987; 35: 1162–1168.
  • 11   Lee  SS,  Lee  PL,  Chen  CF,  Wang  SY,  Chen  KY. Antitumor effects of polysaccharides of Ganoderma lucidum (Curt.:Fr.) P. Karst. (Ling Zhi, Reishi Mushroom) (Ahyllophoromycetideae). Int J Med Mushrooms 2003; 5: 1–16.
  • 12   Watanabe  Y,  Nakanishi  K,  Komatsu  N,  Sakabe  T,  Terakawa  H. Flammulin, an antitumor substance. Bull Chem Soc Jpn 1964; 37: 747–750.
  • 13   Ohno  N,  Miura  NN,  Chiba  N,  Adachi  Y,  Yadomae  T. Comparison of the immunopharmacological activities of triple and single-helical schizophyllan in mice. Biol Pharm Bull 1995; 18: 1242–1247.
  • 14   Chihara  G,  Hamuro  J,  Maeda  YY,  Arai  Y,  Fukuoka  F. Fractionation and purification of polysaccharides with marked antitumor activity, especially lentinan, from Lentinus edodes (Berk.) Sing. (an edible mushroom). Cancer Res 1970; 30: 2776–2781.
  • 15   Sasaki  T,  Takasuka  N. Further study of the structure of lentinan, an anti-tumor polysaccharide from Lentinus edodes. Carbohydr Res 1976; 47: 99–104.
  • 16   Saito  H. Ohki T, Takasuka N, Sasaki T. A 13C-NMR-spectral study of a gel-forming, branched (1→3)-β-D-glucan, (Lentinan) from Lentinus edodes, and its acid-degraded fractions, structure, and dependence of conformation on the molecular weight. Carbohydr Res 1977; 58: 293–305.
  • 17   Saito  H,  Ohki  T,  Sasaki  T. A 13C-nuclear magnetic resonance study of polysaccharide gels. Molecular architecture in the gels consisting of fungal, branched (1→3)-β-D-glucans (lentinan and schizophyllan) as manifested by conformational changes induced by sodium hydroxide. Carbohydr Res 1979; 74: 227–240.
  • 18   Hamuro  J,  Chihara  G. Lentinan, a T-cell oriented immunopotentiator: its experimental and clinical applications and possible mechanism of immune modulation. In:  Fehiche  RL,  Chirigos  MA, eds. Immune Modulation Agents and Their Mechanisms. New York: Marcel Dekker, 1985; 409–436.
  • 19   Maeda  YY,  Chihara  G. The effects of neonatal thymectomy on the antitumor activity of lentinan, carboxymethyl pacymaran and Zymosan and their effects on various immune response. Int J Cancer 1973; 11: 153–161.
  • 20   Maeda  YY,  Hamuro  J,  Chihara  G. The mechanisms of action of anti-tumor polysaccharides: I. The effects of antilymphocyte serum on the antitumor activity of lentinan. Int J Cancer 1971; 8: 41–46.
  • 21   Chihara  G,  Hamuro  J,  Maeda  YY, et al. Antitumor and metastasis-inhibitory activities of lentinan as an immunomodulator: an overview. Cancer Detect Prev Suppl 1987; 1: 423–443.
  • 22   Freunhauf  JP,  Bonnard  GD,  Heberman  RB. The effect of lentinan on production of interleukin-1 by human monocytes. Immunopharmacol 1982; 5: 65–74.
  • 23   Abel  G,  Szöllösi  J,  Chihara  G,  Fachet  J. Effect of lentinan and mannan on phagocytosis of fluorescent latex microbeads by mouse peritoneal macrophages: a flow cytometric study. Int J Immunopharmacol 1989; 11: 615–621.
  • 24   Herlyn  D,  Kaneko  Y,  Powe  J,  Aoki  T,  Koprowski  H. Monoclonal antibody-dependent murine macrophage-mediated cytotoxicity against human tumors is stimulated by lentinan. Jpn J Cancer Res 1985; 76: 37–42.
  • 25   Ladányi  A,  Tímár  J,  Lapis  K. Effect of lentinan on macrophage cytotoxicity against metastatic tumor cells. Cancer Immunol Immunother 1993; 36: 123–126.
  • 26   Kerékgyártó  C,  Virág  L,  Tankó  L,  Chihara  G,  Fachet  J. Strain differences in the cytotoxic activity and TNF production of murine macrophages stimulated by lentinan. Int J Immunopharmacol 1996; 18: 347–353.
  • 27   Carswell  EA,  Old  LJ,  Kassel  RL,  Green  S,  Fiore  N,  Williamson  B. An endotoxin-induced serum factor that causes necrosis of tumors. Proc Natl Acad Sci USA 1975; 72: 3666–3670.
  • 28   Hoffman  OA,  Standing  JE,  Limper  AH. Pneumocystis carinii stimulates tumor necrosis factor-α release from alveolar macrophages through a beta-glucan-mediated mechanism. J Immunol 1993; 150: 3932–3940.
  • 29   Xu  X,  Yasuda  M,  Nakamura-Tsuruta  S,  Mizuno  M,  Ashida  H. β-Glucan from Lentinus edodes inhibits nitric oxide and tumor necrosis factor-α production and phosphorylation of mitogen-activated protein kinases in lipopolysaccharide-stimulated murine RAW 264.7 macrophages. J Biol Chem 2012; 287: 871–878.
  • 30   Mizuno  M,  Nishitani  Y,  Hashimoto  T,  Kanazawa  K. Different suppressive effects of fucoidan and lentinan on IL-8 mRNA expression in in vitro gut inflammation. Biosci Biotech Biochem 2009; 73: 2324–2325.
  • 31   Rice  PJ,  Adams  EL,  Ozment-Skelton  T, et al. Oral delivery and gastrointestinal absorption of soluble glucans stimulate increased resistance to infectious challenge. J Pharmacol Exp Ther. 2005; 314: 1079–1086.
  • 32   Davis  TA,  Volesky  B,  Mucci  A. A review of the biochemistry of heavy metal biosorption by brown algae. Water Res 2003; 37: 4311–4330.
  • 33   Kupfahl  C,  Geginat  G,  Hof  H. Lentinan has a stimulatory effect on innate and adaptive immunity against murine Listeria monocytogenes infection. Int Immunopharmacol 2006; 6: 686–696.
  • 34   Yoshino  S,  Tabata  T,  Hazama  S, et al. Immunoregulatory effects of the antitumor polysaccharide lentinan on Th1/Th2 balance in patients with digestive cancers. Anticancer Res 2000; 20: 4707–4711.
  • 35   Mizuno  M,  Kawakami  S,  Hashimoto  T,  Ashida  H,  Minato  K. Antitumor polysaccharides from edible and medicinal mushrooms and immunomodulating action against murine macrophages. Int J Med Mushrooms 2001; 3: 355–360.
  • 36   Aoki  T. Lentinan: Immune modulation agents and their mechanisms. In:  Fenichel  RL,  Chirgis  MA, eds. Immunology Studies. New York: Marcel Dekker, 1984; 25: 62–77.
  • 37   Mordali  MF,  Mostafavi  H,  Ghods  S,  Hedjaroude  GA. Immunomodulating and anticancer agents in the realm of macromycetes fungi (macrofungi). Int Immunopharmacol 2007; 7: 701–724.
  • 38   Ebina  T,  Fujimiya  Y. Antitumor effect of a peptide-glucan preparation extracted from Agaricus blazei in a double-grafted tumor system in mice. Biotherapy 1998; 11: 259–265.
  • 39   Ito  H,  Shimura  K,  Itoh  H,  Kawade  M. Antitumor effects of a new polysaccharide-protein complex (ATOM) prepared from Agaricus blazei (Iwade strain 101) ”Himematsutake” and its mechanisms in tumor-bearing mice. Anticancer Res 1997; 17: 277–284.
  • 40   Liu  Y,  Fukuwatari  Y,  Okumura  K, et al. Immunomodulating Activity of Agaricus brasiliensis KA21 in Mice and in Human Volunteers. Evid Based Complement Alternat Med 2008; 5: 205–219.
  • 41   Choi  YH,  Yan  GH,  Chai  OH, et al. Inhibition of anaphylaxis-like reaction and mast cell activation by water extract from the fruiting body of Phellinus linteus. Biol Pharm Bull 2006; 29: 1360–1365.
  • 42   Lindequist  U,  Niedermeyer  TH,  Jülich  WD. The pharmacological potential of mushrooms. Evid Based Complement Alternat Med 2005; 2: 285–299.
  • 43   Hossain  S,  Hashimoto  M,  Choudhury  EK, et al. Dietary mushroom (Pleurotus ostreatus) ameliorates atherogenic lipid in hypercholesterolaemic rats. Clin Exp Pharmacol Physiol 2003; 30: 470–475.
  • 44   Taylor  PR,  Brown  GD,  Reid  DM, et al. The β-glucan receptor, dectin-1, is predominantly expressed on the surface of cells of the monocyte/macrophage and neutrophil lineages. J Immunol 2002; 169: 3876–3882.
  • 45   Firenzuoli  F,  Gori  L,  Lombardo  G. The medical mushroom Agaricus blazei Murill: Review of literature and pharmaco-toxicological problems. Evid Based Complement Alternat Med 2008; 5: 3–15.
  • 46   Fujimiya  Y,  Suzuki  Y,  Oshiman  K, et al. Selective tumoricidal effect of soluble proteoglucan extracted from the basidiomycete, Agaricus blazei Murill, mediated via natural killer cell activation and apoptosis. Cancer Immunol Immunother 1998; 46: 147–159.
  • 47   Itoh  H,  Ito  H,  Amano  H,  Noda  H. Inhibitory action of a (1→6)-β-D-glucan-protein complex (F III-2-b) isolated from Agaricus blazei Murill (”himematsutake”) on Meth A fibrosarcoma-bearing mice and its antitumor mechanism. Jpn J Pharmacol 1994; 66: 265–271.
  • 48   Kawagishi  H,  Inagaki  R,  Kanao  T, et al. Fractionation and antitumor activity of the water-insoluble residue of Agaricus blazei fruiting bodies. Carbohydr Res 1989; 186: 267–273.
  • 49   Mizuno  M,  Minato  K,  Ito  H,  Kawade  M,  Terai  H,  Tsuchida  H. Anti-tumor polysaccharide from the mycelium of liquid-cultured Agaricus blazei mill. Biochem Mol Biol Int 1999; 47: 707–714.
  • 50   Morimoto  T,  Takagi  M,  Mizuno  M. Oral administration of Agaricus brasiliensis S. Wasser et al. (Agaricomucetideae) extract downregulates serum immunoglobulin E levels by enhancing Th1 response. Int J Med Mushr 2008; 10: 15–24.
  • 51   Choi  YH,  Yan  GH,  Chai  OH, et al. Inhibitory effects of Agaricus blazei on mast cell-mediated anaphylaxis-like reactions. Biol Pharm Bull 2006; 29: 1366–1371.
  • 52   Bouike  G,  Nishitani  Y,  Shiomi  H, et al. Oral treatment with extract of Agaricus blazei Murill enhanced Th1 response through intestinal epithelial cells and suppressed OVA-sensitized allergy in mice. Evid Based Complement Alternat Med 2011; 2011 doi:10.1155/2011/532180.
  • 53   Mizuno  T,  Ohsawa  K,  Hagiwara  N,  Kuboyama  R. Fractionation and characterization of antitumor polysaccharides from Maitake, Grifola frondosa. Agric Biol Chem 1986; 50: 1679–1688.
  • 54   Wang  G,  Zhang  J,  Mizuno  T, et al. Antitumor active polysaccharides form the Chinese mushroom Songshan lingzhi, the fruiting body of Canoderma tsugae. Biosci Biotechnol Biochem 1993; 57: 894–900.
  • 55   Mizuno  M,  Shiomi  Y,  Minato  K,  Kawakami  S,  Ashida  H,  Tsuchida  H. Fucogalactan isolated from Sarcodon aspratus elicits release of tumor necrosis factor-α and nitric oxide from murine macropahges. Immunopharmacol 2000; 46: 113–121.
 
© 2013 JCBN
feedback
Top