US Pharm. 2009;34(4):HS-16-HS-18.
The number of mushroom species on earth is estimated at 140,000, yet maybe only 10% (approximately 14,000 named species) are known. The three medicinal mushrooms--maitake (Grifola frondosa), shiitake (Lentinula edodes), and reishi (Ganoderma lucidum)--are the most important and widely used mushrooms in alternative medicine. Medicinal mushrooms contain a high density of polysaccharides and triterpenes and over 1,000 other bioactive compounds.1 A variety of bioactive chemicals in medicinal mushrooms have been documented to support immune function and benefit a wide range of medical conditions, including cancer, and to enhance athletic and sexual performance.
People have been interested in medicinal mushrooms and have used them effectively for thousands of years. Many species of mushrooms provide a wealth of protein, fiber, and vitamins B and C, as well as calcium and other minerals. The above three species have demonstrated phenomenal healing potential. In addition, these medicinal mushrooms have been claimed to boost heart health; combat viruses, bacteria, and fungi; reduce inflammation; fight allergies; help balance blood sugar levels; and support the body's detoxification mechanisms.1
Amongst all herbs, fungi profoundly affect humans and are good sources of medicinally useful products. This is because, on a cellular level, fungi and animals have more in common than they have with higher plants. The effectiveness of medicinal mushrooms' biologically active compounds to modulate the immune cells may be due to their structural diversity and variability. Polysaccharides from medicinal mushrooms have the greatest potential for structural variability and the highest capacity for carrying biological information; e.g., four different polysaccharides permute 35,560 unique tetrasaccharides, whereas four amino acids can only form 24 different permutations.2
Mushrooms contain a vast source of powerful new biopharmaceutical products. In particular and most important for modern medicine, they represent an unlimited source of polysaccharides with immuno-stimulating properties. Many, if not all, mushrooms have biologically active polysaccharides in fruit bodies, cultured mycelium, and culture broth. These polysaccharides are of different chemical composition, with most belonging to the group of beta-glucans; these have beta linkages (1 to >3) in the main chain of the glucan and additional beta branch points (1 to >6) that are needed for their biological action. High molecular-weight glucans appear to be more effective than those of low molecular weight.3
Chemical modification is often carried out to improve the biological selectivity and activity of polysaccharides and their clinical qualities by making them water soluble. The main procedures used for chemical improvement are redox-hydrolysis, formolysis, and carboxymethylation. Most of the clinical evidence for immunostimulating activity comes from the commercial polysaccharides lentinan, krestin, and schizophyllan, but polysaccharides of some other promising medicinal mushroom species also show good results.4
Medicinal mushrooms' bioactivity is especially beneficial in clinics when used in conjunction with chemotherapy. Mushroom polysaccharides prevent oncogenesis, show direct antitumor activity against various allogeneic and syngeneic tumors, and are believed to prevent tumor metastasis. Polysaccharides from mushrooms do not attack cancer cells directly but produce their antitumor effects by activating different immune responses in the host. The antitumor action of polysaccharides requires an intact T-cell component; their activity is mediated through a thymus-dependent immune mechanism.9 Adaptogenic mushrooms' practical application is dependent not only on biological properties but also on biotechnological availability.
The three medicinal mushrooms--maitake, shiitake, and reishi--have many overlapping properties; however in this article we attempt to distinguish them from each other from a morphological standpoint and briefly discuss their unique properties.
Ganoderic acids are a class of closely related triterpenes found in Ganoderma mushrooms (reishi). For thousands of years, the fruiting bodies of Ganoderma fungi have been used in traditional medicines in East Asia. Consequently, there have been efforts to identify the chemical constituents that may be responsible for the putative biopharmacologic effects. Dozens of ganoderic acids have been isolated and characterized, of which ganoderic acid A and ganoderic acid B are the most well characterized. Some ganoderic acids have been found to possess biological activities including hepatoprotection, antitumor effects, and 5-alpha reductase inhibition.5
Maitake: This mushroom, also commonly known as sheep's head and hen of the woods, is an edible polypore mushroom. The maitake grows in clusters at the foot of trees, especially the oak. The Japanese call it maitake, literally "dancing mushroom," and it can be found in almost all supermarkets across the nation.
The fungus is native to the northeastern part of Japan and North America and is prized in traditional Chinese and Japanese herbology as an adaptogen, or aid to balance out altered body systems to normal levels. Most Japanese people find its taste and texture enormously appealing, though the mushroom has been alleged to cause allergic reactions in rare cases.
The underground tubers from which maitake arises have been used in traditional Chinese and Japanese medicine to enhance the immune system. It has been reported that whole maitake has the ability to regulate blood pressure and lipids, such as cholesterol, triglycerides, and phospholipids, and may assist in weight loss.
Maitake is rich in minerals (such as potassium, calcium, and magnesium), various vitamins (B2, D2, and niacin), fibers, and amino acids. The active constituent in maitake for enhancing the immune activity was identified in the late 1980s as the protein-bound polysaccharide compound beta-glucan, an ingredient found especially in the Polyporaceae family. Cancer prevention is one of the purported uses of maitake mushroom extract. Maitake is thought to exert its effects through its ability to activate various effector cells, such as macrophages, natural killer cells, T cells, interleukin-1, and superoxide anions, all of which have anticancer activity.6
Shiitake: The shiitake is an edible mushroom native to East Asia and is cultivated and consumed in many Asian countries as well as dried and exported to many countries around the world. It is generally known in the world by its Japanese name,
shiitake, derived from the name of the tree upon whose dead logs it is typically cultivated.
Shiitake have been cultivated for more than 1,000 years. Over centuries, it was found that the mushroom could be used not only as food but also as a remedy for upper-respiratory diseases, poor blood circulation, liver problems, exhaustion and weakness, and is a booster for life energy. It was also believed to prevent premature aging.
Shiitake mushrooms have been researched for their medicinal benefits, most notably their anti-tumor properties in laboratory mice. These studies have also identified the polysaccharide lentinan, a (1-3) beta-D-glucan, as the active compound responsible for the antitumor effects. Extracts from shiitake mushrooms have also been researched for many other immunological benefits, ranging from antiviral properties to possible treatments for severe allergies, as well as arthritis. Shiitake are also one of a few known natural sources of vitamin D2.7
Reishi: Reishi has been rated the top medicinal herb in traditional Chinese medicine for over 2,000 years, with ginseng in second place, and is so highly treasured that it was traded for its own weight in gold and was available only to emperors. It is still the most important herb in the Orient and the most thoroughly researched. The results of many hundreds of scientific and medical studies support traditional health claims. Reishi contains over 200 active ingredients and unique compounds that are the most biologically active obtainable from any plant source. In order to obtain maximum benefit, reishi is best taken as an extract because it is a very tough, woody mushroom and the raw biomass is very difficult to digest. Its dynamic antioxidant action and immune-stimulating effects are why reishi is so highly valued as a longevity herb and called the long life herb.5,8
Reishi is the only known source of a group of triterpenes, known as ganoderic acids, which have a molecular structure similar to steroid hormones. It is a source of biologically active polysaccharides. Unlike many other mushrooms, which have up to 90% water content, fresh reishi contains only about 75% water.9
The antitumoral effect of reishi is not entirely known, but it is probably due to its polysaccharides and triterpenes with a combination of different mechanisms: inhibiting the angiogenesis (formation of arterial vessels that give nutrients to the tumor) and inducing and enhancing the apoptosis of tumoral cells (natural and spontaneous cellular death). There are probably other mechanisms involved in the antitumoral action of reishi, such as an inhibitory effect upon the growth of cells containing masculine or feminine hormonal receptors (androgens and estrogens), of particular interest with regard to breast cancer or prostate cancer.10
The adaptogenic (nontoxic), antiallergenic, and antihypertensive effects are due to the presence of triterpenes. Research indicates that ganoderic acid has some protective effects against liver injury by viruses and other toxic agents in mice, suggesting a potential benefit of this compound in the treatment of liver diseases in humans.11
The Ganoderma extract has been employed to help substantially reduce or eliminate the side effects of radiotherapy and chemotherapy if it is taken before, during, and after the treatments. It has been found clinically to reduce side effects such as hair loss, nausea, vomiting, stomatitis, sore throat, loss of appetite, and insomnia.8
Mushrooms and Cancer
Medicinal mushrooms have latent cancer-preventive properties. Many research studies strongly suggest that regular consumption over prolonged periods significantly reduces the levels of cancer incidence. Cancer Research UK also found increasing experimental evidence that medicinal mushrooms can have a cancer-preventive effect, demonstrating both high antitumor activity and restriction of tumor metastasis.12
The immune system must be fully functional to recognize and eliminate tumor cells. The increased incidence of tumors found in immunosuppressed patients indicates that their immune system has less resistance against cancer. Several major immune-stimulating substances have been isolated from reishi that have extraordinary effects on the maturation, differentiation, and proliferation of many kinds of immune cells. It is reported that reishi is a potent activator of interferon, interleukins, tumor necrosis factor, natural killer cells, T lymphocytes, and tumor-infiltrating lymphocytes. The spontaneous apoptosis of some tumors is usually explained as a function of the individual's own immune system attacking the tumor cells.9,12
It is known that radiotherapy and chemotherapy weaken the patient's immunologic defenses, which may also have been damaged by the cancer itself. Although most patients respond favorably to these therapies, they are nevertheless in danger of opportunistic infections that can invade their systems. Although the new methodologies have been designed to kill the pathogenic cells, they also kill the patient's protective immune cells. Cancer Research UK confirmed that the active compounds in reishi cause a marked increase in the action of macrophages, resulting in a heightened response to foreign cells, whether bacteria, viruses, or tumor cells.10,12 These compounds have been shown to be safe when taken over long periods and appear to reduce the adverse effects of radiotherapy and chemotherapy. These results are in marked contrast to the well-documented adverse side effects associated with most chemotherapeutic compounds and, to a lesser extent, certain immunotherapeutics.12
Recent studies in New Zealand show that a combination of reishi and Cordyceps extracts had beneficial effects on the quality of life for some patients with advanced cancer. Researchers believe that a mixture of the active ingredients from different mushrooms maximizes the immune response by providing multiple stimuli to the body's natural defenses or host defense.12 Cordyceps may be useful for cancer patients due to its enhancement of cell-mediated immunity, oxygen free-radical scavenging, and support for cellular bioenergy systems.
2. Zaidman BZ, Yassin M, Mahajna J, Wasser SP. Medicinal mushroom modulators of molecular targets as cancer therapeutics. Appl Microbiol Biotechnol. 2005;67:453-468.
3. Ko YT, Lin YL. 1,3-beta-glucan quantification by a fluorescence microassay and analysis of its distribution in foods. J Agric Food Chem. 2004;252:3313-3318.
4. Vinogradov E, Wasser SP. The structure of a polysaccharide isolated from Inonotus levis P. Karst. mushroom (Heterobasidiomycetes). Carbohydr Res. 2005; 30:340:2821-2825.
5. Liu, J, Kurashiki K, Shimizu K, Kondo R. Structure-activity relationship for inhibition of 5a-reductase by triterpenoids isolated from Ganoderma lucidum. Bioorganic & Medicinal Chemistry. 2006;14:8654-8660.
6. Kodama N, Komuta K, Nanba H. Can maitake MD-fraction aid cancer patients? Altern Med Rev.
7. Fang N, Li Q, Yu S, et al. Inhibition of growth and induction of apoptosis in human cancer cell lines by an ethyl acetate fraction from shiitake mushrooms. J Alternative & Complementary Medicine. 2006;12:125-132.
8. Kushi LH, Byers T, Doyle C, et al. American Cancer Society guidelines on nutrition and physical activity for cancer prevention: reducing the risk of cancer with healthy food choices and physical activity. CA: a Cancer Journal for Clinicians. 2006;56:254-281.
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11. Li YQ, Wang SF. Anti-hepatitis B activities of ganoderic acid from Ganoderma lucidum. Biotechnol Lett. 2006;28:837-841.
12. Cancer Research UK. www.cancerresearchuk.org. 2002;7:236-239.
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