Many clinically important drugs, such as aspirin, digitoxin, progesterone, cortison and morphine, have been derived directly or indirectly from higher plants, including medicinal mushrooms.
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.
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 in the West for their nutritional value and acceptability as well as their 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 (β-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 studied with little evidence of any toxicity. In Phase I clinical trials, these compounds demonstrate remarkably few adverse reactions. Several purified mushroom 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.
It is to be hoped that Western oncologists will now have the opportunity to assess this area of cancer treatment and to judge whether it will have a realistic role in Western cancer research programmes.
Two compounds, PSK and PSP (derived from mycelial cultures of T. versicolor) have shown worthwhile anti-cancer properties when given with traditional chemotherapeutic agents with no increases in side-effects. A PSK Executive summary has successfully been used in Phase I, II and III clinical trials with cancers of the stomach, oesophagus, nasopharynx, colon, rectum and lung, and with subsets of breast cancer.
The compound PSK gave protection against the immunosuppression that normally is associated with surgery and long-term chemotherapy. PSK continues to be used extensively in Japan as an adjunct to standard radio- and chemotherapy. PSP has been extensively studied by Chinese scientists and oncologists, with little evidence of side-effects.
Clinical trials have shown efficacy in gastric, oesophageal and non-small cell (NSCLC) lung cancers, and PSP has been recognised as a drug by the Chinese Ministry of Public Health.
A significant observation from these studies is the apparent ability of all of the above mushroom-derived polysaccharides when administerded with radiotherapy and/or chemotherapy to significantly reduce the side-effects so often encountered by patients.
Whilst the role of medicinal mushrooms in immunomodulation and anti-cancer activities represents the central theme here, 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 of all medicinal mushrooms or their extracts cannot be guaranteed simply because they have been used for many centuries with apparent safety. However, recent proposals have carefully examined historical usage and have set out reasons for adopting a more cautionary approach but at the same time indicating the way forward to ensure adequate safety and efficacy for an expanding use of mushroom dietary supplements and pharmaceutical products.
The main advantage of using mushroom products with respect to safety (when compared to herbal preparations) are:
• The overwhelming majority of medicinal mushrooms are cultivated commercially (not gathered from the wild). This guarantees proper identification and relatively pure, unadulterated products.
• Mushrooms are easily propagated vegetatively and, thus, kept to one clone. The mycelium can be stored for a long time and the genetic and biochemical consistency may be checked over time.
• The ability to grow most medicinal mushrooms as mycelium in fermenters under controlled conditions with consequent improved product purity. This may well be an important future trend in medicinal mushroom product formation.
Finally, from a holistic consideration, the consumption of whole edible medicinal mushrooms or extracts or concentrates (dietary supplements) may well offer novel, highly palatable, nutritious and health benefiting ingredients to the Western diet as functional foods.by