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PREAMBLE
Many clinically important drugs, such as aspirin, digitoxin, progesterone,
cortison and morphine, have been derived directly or indirectly from higher plants.
Less well-recognised but of great clinical importance are the widely used drugs from
fungi such as the antibiotics, penicillin and griseofulvin, the ergot alkaloids and
cyclosporin.
During the last two decades there has been an increasing recognition of the
role of the human immune system for maintaining good health. Diseases now
associated with immune dysfunction such as cancer, chronic fatigue syndrome,
AIDS/HIV, hepatitis and autoimmune conditions are increasingly coming to the
forefront and being given special attention from medical researchers and clinicians
alike. Historically, the larger fungi, the mushrooms, have had a long and successful
medicinal use especially in traditional Chinese clinical medicine for many forms of
immune disorders. Chinese Pharmacopeias document the use of well over 100
species of mushroom by practitioners of traditional Chinese medicine, for a wide
range of ailments. Many of these mushroom-derived medicinal products are now
produced by major Japanese, Korean and Chinese pharmaceutical companies.
Many of these products are being used worldwide by holistically oriented physicians,
chiropractors, herbalists and naturopathic physicians in a clinical environment. To
date, Western, medicine has made little use of these products in part due to their
complex structure and lack of acceptable pharmaceutical purity.
Mushrooms are not a taxonomic group but do include well over 12,000
species which have macroscopic fruit-bodies, the mushrooms, which are large
enough to be seen by the naked eye. Mushrooms are increasingly being evaluated
pharmacological properties. Increasingly, many are being viewed nutritionally as
functional foods as well as a source of physiologically beneficial and non-invasive
medicines, while others are distinctly non-edible but considered purely as a source of
medicinally beneficial compounds. Some of the most recently isolated and identified
compounds originating from the medicinal mushrooms have shown promising
immunomodulatory, antitumour, cardiovascular, antiviral, antibacterial, antiparasitic,
hepatoprotective and antidiabetic properties. Modern scientific studies of the
medicinal mushrooms have expanded exponentially during the last two decades
primarily in Japan, Korea and China but also in the USA and scientific explanations
of how these compounds function in the animal and human systems are increasingly
appearing in peer-reviewed scientific and medical journals.
Mushroom-derived polysaccharides are now considered as compounds
which are able to modulate animal and human immune responses and to inhibit
certain tumour growths. While mushroom glucans are mostly non-cytotoxic, the
same is not true of glucan-protein complexes. All of these compounds, however,
have been shown to potentiate the host’s innate (non-specific) and acquired
(specific) immune responses and activate many kinds of immune cells that are
important for the maintenance of homeostasis, e.g. host cells (such as cytotoxic
macrophages, monocytes, neutrophils, natural killer cells, dendritic cells) and
chemical messengers (cytokines such as interleukins, interferons, colony stimulating
factors) that trigger complement and acute phase responses. Also, they can be
considered as multi-cytokine inducers able to induce gene expression of various
immunomodulatory cytokines and cytokine receptors. Lymphocytes governing
antibody production (ß-cells) and cell-mediated cytotoxicity (T-cells) are also
stimulated. However, for most of the mushroom-derived anti-cancer compounds, a
detailed understanding of their exact mode of action has not yet been elucidated.
While many mushroom-polysaccharides have been shown to have
considerable antitumour activity in several xenographs only a limited number have
undergone clinical trials. At present the main products submitted for clinical testing
include Lentinan from Lentinus edodes fruit-bodies, Schizophyllan from
Schizophyllum commune mycelial broth, PSK and PSP, from mycelial cultures of
Trametes versicolor and Grifron-D from fruit-bodies of Grifola frondosa. All have
been through Phase I, II and III clinical trials mainly in Japan and China but now in
US. However, in many cases the standards of these trials may not meet current
Western regulatory requirements. In many cases there have been significant
improvements in quality of life and survival. Increasingly, several of these
compounds are now used extensively in Japan, Korea and China, as adjuncts to
standard radio- and chemotherapy. While most of these clinical studies have used
extracts from individual medicinal mushrooms, some recent studies from Japan have
shown that mixtures of extracts from several known medicinal mushrooms, when
taken as a supplement, have shown beneficial effects on the quality of life for some
advanced cancer patients.
Perhaps the most encouraging observations from most of these studies is the
ability of the mushroom-derived polysaccharides when taken prior to and during
radiotherapy and/or chemotherapy to significantly reduce the side-effects of these
treatments.
The safety criteria for the mushroom polysaccharides have been exhaustively
polysaccharides have been in clinical use in Japan, Korea, China and more recently
in the USA for several years with no reports of any short-term or long-term toxicity.
Clinical efficacy of the mushroom polysaccharides will depend on
understanding their precise scope of activity verifiable through in vitro and in vivo
animal and tissue culture tests and human clinical trials, dose range, extraction
methods, source and purity of the raw fungal material, duration and frequency of
administration, and accuracy in matching the extracts to each particular patient
based on traditional and modern diagnostic methods.
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