An immunomodulating substance, a biological response modifier (BRM) or biotherapy is important for the treatment of cancer and infectious diseases. b-Glucan is a well-known BRM which is widely distributed in nature and used as a medicine and food. [1][2][3][4][5] The effects of "Lentinan" from Lentinus edodes and "Sonifilan" (SPG) from Schizophyllum commune in cancer therapy have been clinically proven.6,7) We have already developed b-glucans, GRN from Grifola frondosa, [8][9][10] SSG and TSG from Sclerotinia sclerotiorum, [11][12][13] OL-2 from Omphalia lapidescens, 14) PVS and PVG from Peziza vesiculosa, 15) CSBG from Candida spp., 16) OX-ZYM from a yeast cell preparation, zymosan, 17,18) and SCG from Sparaccis crispa. 19) We have also prepared several carboxymethyl, hydroxyethyl, sulfate, and polyol derivatives of the above b-glucans.20) In addition, we have analyzed the mechanism of b-glucan mediated immunopharmacological activity and identified the conformation dependent and independent activity. [21][22][23][24][25] These rather complicated relationships between structure and activity suggest the contribution of multiple receptor-ligand interactions in b-glucan mediated immunopotentiation.The incidence of cancer is gradually increasing and the spectrum of cancer-prone organs is changing each year. In addition to surgery, irradiation, and chemotherapy, immunotherapy is believed to be an important cancer therapy. 26)Immunotherapy and biotherapy include various approaches, such as BRMs, cytokines, lymphocyte transplantation, gene therapy, and herbal and alternative medicines. Clinical trials of these therapies are being widely carried out, and clinical evidence suggests their efficacy, although the precise mechanisms are still difficult to understand. The development of additional b-glucans is still needed for better biotherapy and to understand the molecular mechanisms.Agaricus blazei is a medical mushroom widely eaten and prescribed in Japan. There are various kind of health foods containing A. blazei and/or its extracts, but the molecular mechanisms of its action is far beyond complete understanding. The most anticipated pharmacological effect of A. blazei is modulation of the immune system against cancer. In the last decade, there have been several studies which focused on an antitumor polysaccharide from A. blazei, i.e., 1,6-b-glucan, glucan-protein complex, a-glucan, and heteroglycan. 27-34) Antitumor polysaccharides were screened not only in the fruitbody but also the liquid cultured medium and mycelium. One of the best characterized components, FIII-2-b, was prepared from the sodium hydroxide extract of the fruit body, and the structure was analyzed by methylation and NMR analyses. Contribution of a protein moiety to the activity of FIII-2-b was speculated by loss of the activity by partial formolysis. In the preliminary investigation, we have also determined that the major carbohydrate component of the fruit body of A. blazei is 1,6-b-glucan; however, we have already shown that a linear 1,6-b-glucan,...

We performed studies on murine models and human volunteers to examine the immunoenhancing effects of the naturally outdoor-cultivated fruit body of Agaricus brasiliensis KA21 (i.e. Agaricus blazei). Antitumor, leukocyte-enhancing, hepatopathy-alleviating and endotoxin shock-alleviating effects were found in mice. In the human study, percentage body fat, percentage visceral fat, blood cholesterol level and blood glucose level were decreased, and natural killer cell activity was increased. Taken together, the results strongly suggest that the A. brasiliensis fruit body is useful as a health-promoting food.

High-molecular weight polymerised polyphenols have been shown to exhibit anti-influenza virus, anti-HIV, and anti-cancer activities. The purpose of this study was to evaluate the immunomodulating activities of enzymatically polymerised polyphenols, and to clarify the underlying mechanisms of their effects. The cytokine-inducing activity of the enzymatically polymerised polyphenols derived from caffeic acid (CA), ferulic acid (FA), and p-coumaric acid (CoA) was investigated using murine splenocytes. Polymerised polyphenols, but not non-polymerised polyphenols, induced cytokine synthesis in murine splenocytes. Polymerised polyphenols induced several cytokines in murine splenocytes, with interferon-γ (IFN-γ) and granulocyte-macrophage colony-stimulating factor (GM-CSF) being the most prominent. The underlying mechanisms of the effects of the polymerised polyphenols were then studied using neutralising antibodies and fluorescent-activated cell sorting (FACS) analysis. Our results show that polymerised polyphenols increased IFN-γ and GM-CSF production in splenocytes. In addition, the anti-CD4 neutralised monoclonal antibody (mAb) inhibited polymerised polyphenol-induced IFN-γ and GM-CSF secretion. Moreover, polymerised polyphenols bound directly to a recombinant CD4 protein, and FACS analysis confirmed that interaction occurs between polymerised polyphenols and CD4 molecules expressed on the cell surface. In this study, we clearly demonstrated that enzymatic polymerisation confers immunoactivating potential to phenylpropanoic acids, and CD4 plays a key role in their cytokine-inducing activity.

No abstract

The Royal Sun medicinal mushroom, Agaricus brasiliensis, is used as a natural health product. In Japan, however, the quality control of some of these mushroom products has been viewed as a safety problem. Focusing on the quality control of A. brasiliensis KA21, we have performed several safety studies. To date, we have established evidence that this mushroom can be used safely as an immunostimulant and to mediate biochemical parameters associated with obesity or diabetes. Furthermore, to improve the manufacturing process of this mushroom, we have studied the relationship between its pharmaceutical actions and the conditions of its cultivation and thermal management. The purpose of this review is to report the findings of basic and clinical studies of the fruit body of A. brasiliensis KA21.