Coriolus (or Trametes) versicolor is the most thoroughly clinically researched mushroom. An extract of Coriolus versicolor known as PSK is sold in Europe and Japan. It is the best-selling cancer drug in the world and recently accounted for more than 25% of Japan’s total national expenditure for anticancer agents. In addition to possessing many different antitumor properties, it is also an immunostimulant; demonstrates anti-viral activity; enhances T-cell proliferation; and has been shown to improve both disease-free and survival rates in cancer patients. In an 8-year clinical test of breast cancer patients, and in another 5-year study, it was shown that the polysaccharide compounds contained within Coriolus versicolor work particularly well as an adjuvant for cancer therapies, exhibiting diverse biological activities.
Coriolus: One Of The Most Powerful Immune Modulators Known
Recent scientific research has shown that medicinal mushrooms grown on vegetable sources (such as millet, rice bran, buckwheat, barley, etc.) enzymatically activate a process whereby complex cross-linked polysaccharides from the vegetable sources are converted to biologically active immunomodulators (also known as biological response modifiers). As you will see from the discussion below, the polysaccharides produced by this process are effective and safe immune stimulants.
Medicinal mushroom research has focused on discovering compounds that can modulate positively or negatively the biological response of immune cells. Certain mushroom derived-glucans and polysaccharide-bound proteins have been shown to act as immunomodulators or biological response modifiers (BRMs), where these polymers interact with the immune system to upregulate or downregulate specific aspects of the responses of the host and this may result in various therapeutic effects. Whether certain compounds enhance or suppress immune responses can depend on a number of factors including dosage, route of administration, timing and frequency of administration, mechanism of action or the site of activity. Many mushroom-derived polysaccharides appear to fit the accepted criteria for BRM compounds. They cause no harm and place no additional stress on the body, they assist the body to adapt to the various environmental and psychological stresses, and they have a non-specific action on the body, supporting all the major systems, including nervous, hormonal, and immune systems, as well as regulatory functions.
The anti-tumor polysaccharides isolated from mushrooms (fruit-body, submerged, cultured mycelial biomass or liquid culture broth) are either water-soluble β-D-glucans, β-D-glucans with heterosaccharide chains of xylose, mannose, galactose, or uronic acid or β-D-glucan-protein complexes – proteoglycans.
While the role of medicinal mushrooms in immunomodulation and anti-cancer activities represents the central theme of much of the conducted research, it is pertinent to observe that many of the medicinal mushrooms have been highly valued for other medicinal properties including hypercholesterolemia, high blood pressure, diabetes, anti-viral, anti-bacteria, and antioxidant and free radical scavenging.
The safety criteria for mushroom-derived β-glucans have been exhaustively carried out in pre-clinical experiments. Acute, subacute, and chronic toxicity tests have been carried out together with administration during pregnancy and lactation with no adverse effects. There were no anaphylactic reactions and no effects in mutagenicity and haemolysis tests, blood coagulation and a wide range of other regulatory tests. There was no evidence of genotoxicity. Similar results have been obtained with other β-glucans. When applied to humans in Phase 1 clinical tests, the β-glucans demonstrate remarkably few adverse clinical reactions.
In the 2001 report Medicinal Mushrooms: Their Therapeutic Properties and Current Medical Usage with Special Emphasis on Cancer Treatments, a wide variety of mushroom polysaccharides, including Lentinan (from L. edodes), Schizophyllan (from S. commune), PSK and PSP (from Trametes versicolor), and Grifron-D (from the Maitake mushroom G. frondosa) and others are described, and their properties are shown to satisfy the criteria for BRMs. Many of these mushroom-derived polymers potentiate the host’s innate (non-specific) and acquired (specific) immune responses in a similar manner, where they activate many kinds of immune cells that are vitally important for the maintenance of homeostasis. Key innate responses that are stimulated by these mushroom derived-β-glucans or polysaccharide-protein complexes include host T-cells (such as cytotoxic macrophages, monocytes, neutrophils, natural killer cells, and dendritic cells) and chemical messengers (cytokines such as interleukins, interferon and colony stimulating factors) that trigger complement and acute phase responses. Moreover, mushroom polysaccharides or polysaccharide-protein complexes are considered as multi-cytokine inducers that are able to induce gene expression of various immunomodulatory cytokines and cytokine receptors. In addition, acquired responses are also enlisted, where lymphocytes that govern antibody production (B cells) and cell-mediated cytotoxicity (T-cells) are stimulated. While the immune system is shrouded in tremendous complexity, our current understanding shows that it is regulated in an orchestrated dynamic manner.
Mushroom-derived polysaccharides have shown anti-tumour activities in both pre-clinical models and in clinical trials. Although the mechanism of their anti-tumour action is still not completely clear, Lentinan, Schizophyllan, PSP, PSK and other mushroom polysaccharides appear to mediate their anti-tumour activity by activation or augmentation of the host’s immune system (via stimulated cytotoxic macrophages, cytotoxic T-cells and antibody-mediated cytoxicity of targeted cancer cells), rather than direct cytotoxicity. Thus, both cell-mediated immune responses against the target T-cells initiated by macrophage-lymphocyte interactions and cytoxicity induced by antibodies to target T-cells are believed to contribute to the elimination of targeted tumour cells. Recent evidence suggests that several mushroom polysaccharides may also possess cytotoxic properties. Grifron-D from G. fondosa mushroom was reported to induce apoptosis (programmed cell death) in human prostate cancer cell-lines.