Review Article

Therapeutic Potential of

Mahendra Rai1*, Girish Tidke1 and Soloman P Wasser2 1Department of Biotechnology, Amravati University, Amravati – 444 602, Maharashtra, India 2International Centre for Cryptogamic Plants and Fungi, Institute of Evolution University of Haifa, Mt. Carmel, Haifa, 31905, Israel *Correspondent author, E-mail: [email protected] Received 15 April 2004; Revised 16 March 2005 human consumption, and about 650 of Abstract these possess medicinal properties. In the second half of twentieth century, the Mushrooms are an important natural source of foods and medicines. Traditional aboriginals knew the medicinal importance of edible and wild mushrooms and these are now producing technologies have being screened for their bioactivity in various ailments. Mushrooms represent a major and untapped grown enormously and the value of world source of potent new pharmaceutical products. A wide range of activities including antitumour, mushroom production was estimated to cardiovascular and are reported in mushrooms. In developing countries like India be worth about eighteen billion US dollar. mushroom progress is a boon in the field of food, medicine, and in generating employment. The Many pharmaceutical substances with alternative systems of medicine utilize the curative properties of mushrooms. The present review is aimed to discuss biological activities of mushrooms and their roles in various human diseases. potent and unique properties were recently extracted from mushrooms and make their Keywords: Mushrooms, Antimicrobial, Bioactivity, Biomedical, Cardiovascular, Therapeutics. way all around the world. The IPC code; Int. cl.7— A61K 35/84, A61P 9/00, A61P 31/00, A61P 35/00 Ganodermataceae family includes about forty species with hard basidiocarp Introduction coli (Ishikawa et al, 2001). The use of (fruit bodies). In Chinese folklore the fruit mushrooms as medicine was mentioned body of Ganoderma lucidum (Fr.) P. Mushrooms can be either by Berkeley (1857), who hypogeous or epigeous, large enough to reported that be seen with the naked eye and usually gigantea (Giant ) picked by hands. They produce fleshy fruit and C. caelata can be used bodies belonging to Basidiomycotina and in burnt cases due to their Ascomycotina. The edible nature of anaesthetic nature. Calvatia mushrooms is now well-known. Usually spp. are also used to stop Agaricus, Pleurotus and Volvariella bleeding from wounds. A spp. are eaten all over the world in wood decaying , general, and tropical countries, in Fomitopsis officinalis, particular. However, the medicinal which contains agaricin, is uses of the mushroom still need to be used in many medicines. worked out for their biological activities Mushrooms due to a fast increasing number of represent a major and as yet, multidrug resistance in pathogenic largely untapped source of microbes like Candida spp., potent new pharmaceutical Staphylococcus aureus, S. products. Out of epidermidis, Streptococcus spp., approximately 15,000 known Enterococcus spp. and Escherichia species, 2,000 are safe for Agaricus sp.

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Agaricus bisporus, Pholiota doses recommended by various doctors nameko, Tricholoma matsutake and and physicians. Auricularia auricula-judae possess The traditional uses of the antitumour effects also. In USA and Japan mushroom are known to the aboriginals Maitake () and of Africa, India, Brazil and other Shiitake (Lentinus edodes) have been countries. In Nigeria, Puff balls reported to be inhibitory to the AIDS virus. (Lycoperdon pusilum and Calvatia The important medicinal mushroom gigantea) are used to cure sores, species with antitumour polysaccharides abrasion or bruises, deep cut, Ganoderma sp. in fruit bodies and cultured mycelium are: haemorrhages, and urinary infections Tremella fuciformis, Schizophyllum (Buswell & Chang, 1993). In India, Karst. () has been regarded as a commune, Dendropolyporus Ganoderma lucidum is used in panacea for all types of diseases like umbellatus, Grifola frondosa, asthma by the Baiga tribe of Central India, hepatopathy, chronic hepatitis, nephritis, Hericium erinaceus, Inonotus Agaricus spp. is used in goiter and hypertension, hyperlipidemic, arthritis, obliquus, Ganoderma lucidum, G. Lycoperdon pusilum in wound healing neurasthenia, insomnia, bronchitis, applanatum, Lentinus edodes, and also for controlling bleeding. asthma, gastric ulcer, arteriosclerosis, Flammulina velutipes, etc. They The medicinal and commercial leukopenia, diabetes and anorexia. stimulate macrophage activity and potential of bioactive substances derived In developing countries like India strengthen immune systems. from higher Basidiomycetes mushrooms are a boon for progress in In traditional Chinese medicine mushrooms (edible and medicinal) and the fields of food, medicine and extracts from many medicinal mushrooms its proprietary biotechnology process in unemployment. Mushrooms in the have long been used for a wide range of order to produce new dietary supplements twentieth century are well-known to diseases. Modern scientific and medical and, at a later stage, new pharmaceutical people all over the Asian countries as an studies support many of these claims. The products, have been exploited. Extensive important bio-source of novel secondary main areas of medicinal studies include tests to obtain substances for metabolites. In India, particularly the anticancer, cholesterol and blood anticancer, anticholesterol, antidiabetic, alternative systems of medicine, utilize the pressure lowering, liver protective, hepatoprotective and sexual potential curative properties of mushrooms. The antifibrotic, antiinflammatory, antidiabetic, activities have been performed in vitro secondary metabolites of these and antimicrobial activity (Ooi & Liu, and in vivo. Several dietary supplements mushrooms are chemically diverse and 1999; Wasser & Weis, 1999a, 1999b; from fungal biomass are produced and possess a wide spectrum of biological Gunde-Cimerman, 1999; Wasser, 2005 a, tested. These supplements contain many activities, which are explored in traditional 2005 b; Wasser & Didukh, 2005). bioactive substances with mild health medicines and in new targets of molecular In addition to the therapeutic promoting and sustaining effects. They do biology. They have important present potential, hundreds of the mushrooms are not specifically treat disease, rather, they status and possess a potential to design being explored the world over to study and are used as functional food, on a daily future strategies for human health values. reveal their biotechnological potential. basis, strengthening and perfecting many Pharmaceuticals worth $700 million US Wasser (2002) has screened more than different physiological systems of the dollars are produced annually in Japan one hundred species for human body. Two new dietary supplements alone from Lentinus, Trametes, their antimicrobial and other such with cholesterol lowering, antidiabetic and Schizophyllum, and Ganoderma. properties. The product made from the immunostimulating properties have been Extracts of various edible fungi, viz. mushroom is being sold in the national produced and patented (Wasser, 2000). Lentinus edodes, Flammulina and international markets. They are The present review is aimed to velutipes, Pleurotus ostreatus, available with prior clinical trials and summarize the therapeutic importance of

Vol 4(4) July-August 2005 247 Review Article various mushrooms and explore further antitumour activity. Flammulina enhancing various mediators such as research in various areas and the future velutipes, exhibits strong antitumour lymphokines and IL-1 (Nanba, 1993). prospects in order to develop a new activity against Sarcoma 180, Lewis cancer Grifolan (β-glucan), xyloglucan, generation of modern drugs. of lung, and B-16 melanoma (Ikekawa, annoglucan, fucomannoglucan, 1995). The antitumour glycoprotein compounds isolated from this fungus Antitumour properties proflamin found in mycelia of F. possess antitumour property (Mizuno, velutipes is effective against allogeneic 1997, 1998). Heteroglucan protein, The fruiting body of mushroom and syngeneic tumours by oral mannogalactofucan, heteroxylan, Agaricus brasiliensis S. Wasser administration. Proflamin augments galactomannoglucan, compounds isolated et al (=blazei Murrill ss. Heinem) antibody formation and activates from submerged cultures of G. frondosa having a glycoprotein (50.2% sugar and lymphocyte blastogenesis (Ikekawa, 1995; have also shown antitumour activity 43.3% protein) and three ergosterol Ikekawa et al, 1985). A polysaccharide, (Zhuang et al, 1994a, 1994b). The derivatives (I, II, III), showed antitumour PA3 DE, isolated from this fungus has also antitumour properties of Lentinus activity. A β-D-glucan polysaccharide shown inhibitory activity against implanted edodes are attributed to the isolated from this mushroom also Sarcoma 180 (solid tumour) in mice. polysaccharide lentinan and emitanin. exhibited immunostimulative and The triterpenoids isolated from Lentinan is now used as an antitumour antitumour activity (Mizuno et al, 1990; Ganoderma lucidum are C3 epimers drug (Chihara et al, 1970). Lentinan is Kawagishi et al, 1989). However, a higher and C-3/C -15 positional isomers in pairs. nontoxic to tumour cells, but inhibits antitumour activity was observed in A β-D-glucan isolated from this fungus tumour growth by stimulating the immune another xyloglucan protein complex showed immunostimulative antitumour system (Chihara, 1978). obtained from the 5% NaOH solution activity. A glycoprotein fraction GL isolated The mushroom Pleurotus (Mizuno et al, 1990). A glycoprotein from the hot water soluble components sajor-caju contains protein having fraction obtained from A. campestris of the basidiocarp of G. lucidum showed polysaccharide xyloglucan, xylanproteins, also exhibited antitumour activity against 81% inhibition of tumour growth in mice. has shown Sarcoma 180 in ICR mice; the protein GL exerted the antitumour activity through antitumour moiety was composed of 17 amino acids immunopotentiation and not through activity against (Jeong et al, 1990). Along with direct cytotoxicity against the tumours. Sarcoma 180 ergosterol, six steroids are also isolated (Chem Abstr, 1992). From the culture tumour cells in from an acetone extract of A. mycelium of G. lucidum, Toth et al vivo (Zhuang brasiliensis fruit bodies. Out of the six (1983a, 1983b) isolated ganoderic acids et al, 1993). steroids, three of them effectively inhibited Z, Y, X, W, V and U which were found to be Trametes cell proliferation of cervical cancer cell cytotoxic to hepatoma cells in vitro. ( Coriolus) (HeLa cells) (Mizuno, 2002). The acidic Glucuronoglucan, xyloglucan, mannoglucan, versicolor was heteroglycans isolated from Auricularia xylomannoglucan and other active found to possess auricula-judae exhibited antitumour heteroglucans and their potential antitumour and activity on implanted Sarcoma 180 (Ukai complexes, extracted from this species immunostimulant et al, 1983; Misaki et al, 1981). were purified using salts, alkali and DMSO properties. Extracts of fruiting bodies of (Mizuno et al, 1984; Willard, 1990; From the Pleurotus sajor-caju Boletus edulis have shown 100% Wasser & Weis, 1997b). carpophores of inhibition against Sarcoma 180 and 90% A protein with β-glucan isolated this fungus, a polysaccharide fraction, built inhibition against Ehrlich carcinoma in from Grifola frondosa extract exhibits up of glucose (96.44%), xylose (2.16%) and mice (Ying et al, 1987). Calvacin was antitumour activity by potentiating anti- mannose (1.73%), exhibiting antitumour isolated from Calvatia gigantea with tumour cellular functions by directly activity was isolated. PSP, a glycopeptide

248 Natural Product Radiance Review Article possessing antitumour and mushrooms could be recommended as a immunostimulant activities was also natural cholesterol lowering substance obtained from the ethanol extract of T. within the human diet (Gunde-Cimerman, versicolor mycelium (Yang & Wang, 1999). 1994). In western countries coronary artery disease is the major cause of death, Cardiovascular and while hypercholesterolemia is a risk hypercholesterolemic factor, which causes the hardening of the properties arteries. In humans, 50% or more of total cholesterol I is derived from de novo Lentinus edodes Lentinus edodes can lower synthesis. It has been proven that Shiitake both blood pressure and free cholesterol mushroom is used to lower blood serum Actinomycetes and Streptomycetes. in plasma, as well as accelerate cholesterol (BSC) via a factor known as The water extract of Lentinus accumulation of lipids in liver by eritadenine, which is also called edodes demonstrated growth- removing them from circulation. In most “Lentinacin” or “Lyntisine”. It is known enhancing effects on colon inhabiting developed countries, the common cause that, apparently, eritadenine reduces BSC beneficial lactic acid bacteria, of death is coronary artery disease. The in mice, not by inhibition of cholesterol Lactobacillus brevis and main risk factors are hypercholesteromia biosynthesis, but by the acceleration of Bifidobacteria brevie. The effective and dislipoproteinemia, diabetes, excretion of ingested cholesterol and its factor in the extract is considered to disturbance in blood platelet binding and metabolic decomposition (Suzuki & be the disaccharide sugar, trehalose. high blood pressure. The initial steps for Oshima, 1974, 1976). Eritadenine also The L. edodes extract can improve the the prevention and treatment of CAD and lower the blood levels of cholesterol and beneficial intestinal flora of the gut and hypercholesterolemia are the modification lipids in animals. reduced harmful effects of certain in regime with a diet low in fats and bacterial enzymes such as saturated fatty acids in crude fibers. Antimicrobial properties β-glucosidase, β-glucorinidase and Clinical intervention studies have clearly tryptophase as well as reducing colon demonstrated therapeutic importance of In recent years Basidiomycetes cancer formation (Bae, 1997). It is correcting hypercholesterolemia (Albert and other higher fungi including some clear from the results that mushrooms et al,1989). recognized medicinal mushrooms have also have antimicrobial properties. Mevinolin is produced been re-investigated as sources of novel The bioactive compounds like commercially from the filamentous antibiotics mainly as a result of increasing mniopetals, oudemansin, lanostane and fungus Aspergillus tereus. This is the difficulty and the cost of isolating novel strobilurin possess potent antimicrobial first specific inhibitor of microzomal bioactive compounds from the activity (Table 1). Their dose enzyme that occurs early in the compensation and the mode of action is biosynthetic pathway to cholesterol subject for research for new generation formation. The addition of 4% dried researchers. Clearly, the antimicrobial Pleurotus to a high cholesterol diet potential of extract of several medicinal reduced cholesterol accumulation in the mushroom type and indeed other serum effectively and liver of experimental Basidiomycetes not yet exploited, must rats. Cholesterol lowering effect of the warrant further examination. mushroom Pleurotus ostreatus in The heavy molecular weight cell hypercholesterolemic rats is also reported. wall polysaccharides, for example, PSP It has been suggested that Pleurotus Lentinus edodes from Trametes versicolor inhibits

Vol 4(4) July-August 2005 249 Review Article growth of infectious yeast, such as Lentinus edodes, Coprinus mix and another 26 comparable patients Candida albicans (Tsukagoshi, 1984; comatus and Oudemansiella receiving the accepted pharmaceutical Sakagami, 1991, 1993). Antitumour mucida have been reported to have drug Polyactin-A as a control group. All polysaccharides inhibit bacteria such as antifungal and antibacterial properties. patients were in the middle-late stages Bacillus subtilis, Staphylococcus (stage 3 and 4) of cancer. The experiment aureus, Escherichia coli and Clinical trials and other uses concludes that the tablets of mixed Pseudomonas aeruginosa. of mushrooms polysaccharides, made up of the six species Hericium erinaceus shows strong of medicinal mushrooms, can become a antimicrobial activity against a broad Clinical trials were conducted on new health product to improve immunity range of infectious agents. Compounds 56 cancer patients, 30 were chosen to with high effectiveness and nontoxicity. extracted from Agaricus bisporus, receive the medicinal mushroom extract However, further trials are needed.

Table 1 : Compounds showing antimicrobial activity

Mushrooms Bioactive compounds Bioactivity Reference

Cheimonophylum Cheimonophyllon A-E Antibacterial, Stadler et al, 1994 candissimum weak antifungal Clitocybe cyathiformis Cyathiformine A Antibacterial and Arnone et al, 1993 antifungal Clitocybe diatreta Diatretol Antibacterial Arnone et al, 1996 Coprinus atramentarius Illudin C2, Illudin C3 Antimicrobial Lee et al, 1996 Crepidotus fulvotomentosus Strobilurin E Antifungal Weber et al, 1989 Favolaschia pustulosa 9-methoxystrobilurin L Antifungal and Antibacterial Wood et al, 1996 Favolaschia sp. Favolon Antifungal Anke et al, 1995 Flagelloscypha pilatii Pilatin Antibiotic Heim et al, 1988 Ganoderma lucidum Ganoderan Antiviral Wasser, 2005 Lentinus edodes Lentinan Antiviral Mizuno, 2000 Mniopetalum sp. Mniopetals Antimicrobial Kuschel et al, 1994 Mycena sp. Strobilurin M, Antifungal, Cytostatic, Daferner et al, 1998 Tetrachloropyrocatechol Antifungal, Antibacterial Omphalotus illudens Illudinic acid Antibacterial Dufresne et al, 1997 Oudemansiella radicata Oudemansin x Antifungal Anke et al, 1990 Poria cocos Lanostane Phospholipase A2 Cuellar et al, 1996 inhibitor (group of antiinflammatory agents)

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The polysaccharides extracted from assessable patients, 46 (32.2%) had the rats. This activity is due to the Agaricus brasiliensis, Grifola progressive disease before or at the six Ganoderic acids C and D, which are also frondosa, Lentinus edodes, weeks evaluation point (range: 5 days-6 responsible for the treatment of asthma Ganoderma lucidum, Trametes weeks). There was no significant change and allergy. The polysaccharides and versicolor and Cordyceps sinensis in the Functional Assessment of Cancer triterpenoids have also shown the anti- HIV are used to produce tablets for inhibiting Therapy-General (FACT-G) scores in 85 activity. They also show protective effects the growth of tumours and improving the assessable patients. In the group with on liver in animal and human studies immunity. stable disease, FACT-G scores improved in (Wasser & Weis, 1997b). The products of Ganoderma 23 patients, remained unchanged in five, Ganopoly is well-tolerated and lucidum are prescribed in various forms; and declined in one. Within this group, appears to be active against HBV patients it can be injected as a solution of the median change from the baseline with chronic hepatitis B. The mechanism powdered spores or given as syrup. It can score to the 6 and 12 weeks was +7.6 for hepatoprotective effects of be taken as tea, soup, capsules, tinctures, and +10.3, both statistically significant G. lucidum have been largely undefined. or bolus. In tincture form, the dose given (P < 0.05). For the 38 patients with SD, However, accumulating evidence suggests is 10 ml thrice daily. In case of syrup the the median change from the baseline several possible mechanisms, which dose is 4-6 ml/day. The dried mushroom score was 28.1 ± 10.2 weeks. This include antioxidants and radical (200-300 g) is prepared in water and given indicates that Ganopoly may have an scavenging activity, modulation of hepatic as a drink, the recommended dose is 3-5 adjunct role in the treatment of patients Phase I and II enzymes inhibition of times daily (Ying et al, 1987; Zhuang, with advanced cancer although objective β-glucuronidase, antifibrotic and antiviral 1993). responses were not observed in the study activity, modulation of NO production, In Japan, Ganoderma (Wasser & Weis, 1997a). maintenance of hepatocellular calcium lucidum is used for the treatment of the G. lucidum and other homeostasis and immunomodulating cancer (Willard, 1990). The results mushrooms like G. applanatum, effects. G. lucidum also cures lung and obtained after application shows that the Lentinus edodes, Flammulina heart dysfunction. Clinical studies on this patient sleeps well with a healthier feeling velutipes, Grifola frondosa from were conducted in China in which 200 and has an increased appetite; Reishi also China, Korea, Japan and India have been patients with chronic bronchitis were provides relief from angina pectoris. used in many clinical studies with animals given G. lucidum in tablet form and Injection of spore powder is effective in and humans, reporting the beneficial 60-90% patients showed marked curing progressive deterioration, atrophy results. The high-molecular-weight improvement with increased appetite. It and muscles stiffness. The effect of polysaccharides from the cell walls of also reduced blood and plasma viscosity elevation changes has been prevented and G. lucidum are physiologically active. in hypertensive patients with cured by tablets of mushroom spores. They are used against various diseases like hyperlipidaemia. The extracts of this In an experimental study for diabetes, Alzheimer’s disease, retinal mushroom were reported to reduce blood therapeutic application of G. lucidum, pigmentary degeneration, atrophic cholesterol and blood pressure and also 143 patients with advanced previously myotonous hepatodymia, rhinitis, treat arrhythmia (Ding, 1987; Cheng treated cancer were given an oral G. leucopoenia, insomnia, dyspnea, et al, 1993). G. lucidum has also shown lucidum polysaccharide extract of 1800 neurasthenia and duodenal ulcers. The hypoglycaemic and hypolipidemic mg three times daily for 12 weeks. Twenty- water extract from fruit body had activities. In a study, 71 patients with seven patients were not assessable for inhibitory activity on histamine release confirmed type II diabetes mellitus were response and toxicity, because they were from rat peritoneal mast cells, induced by cured and had best results. This study unable to track for follow-up or refused compound 48/80 or antigen-antibody demonstrated that Ganopoly is efficacious further therapy before the 12 weeks of reaction and on passive cutaneous and safe in lowering blood glucose treatment were up. Of the 100 fully anaphylaxis reaction in guinea pigs and concentrations.

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The practitioner experiences in treating certain viral diseases, inducing produced for protection against UV along with preliminary clinical reports HIV and Epstein Barr Virus (EBV), the radiation. (Ying et al, 1987). Current indicate that immunostimulating cause of mononucleosis. The G. lucidum biomedical applications of polysaccharides of G. lucidum are useful is one of the ingredients in skin lotions G. lucidum are given in Table 2.

Table 2 : Current biomedical applications of Ganoderma lucidum

Applications References

A. Immunomodulating effects Chang, 1994 1. Anticancer Mizuno, 1995a, 1995b, 1995c 2. Antiviral (e.g., anti-HIV) Kim et al, 1994 3. Antibacterial Yoon et al, 1994 4. Therapy of auto-immune disorders Chang, 1993, 1994, 1996 B. Cardiovascular disorders 1. Coronary dilation and increasing coronary circulation Soo, 1994, 1996 2. Anti-hyperlipidemic, and antiplatelet hypoglycaemic Chang & But, 1986 aggregation (blood clots) C. Cancer therapy 1. Maintain leucocyte count Chang, 1994; Soo, 1994 2. Enhance the Soo, 1996 3. Reduction of toxicity and elimination of Chang & But, 1986; Hu & But, 1987; Chen & Yu, 1993; induced leucopenia (low blood leucocytes) Mizuno, 1995 a, 1995 b, 1995 c by chemotherapy 4. Remission to prevent relapses Chang, 1994 D. Remission of cancer and hepatitis B treatment Ventura & Messerli, 1987; Chang, 1993; Mizuno, 1995a, 1995b, 1995c E. Enhancing oxygen utilization 1. Relief of discomfort of high altitude stress, headaches, Dharmananda, 1988 dizziness, nausea & insomnia 2. Relief of oxygen deprivation caused by coronary Mizuno, 1995c arteries blocked by atheromas, spasms or clots F. Anti-ageing, anti-oxidant free radical scavengers Mizuno, 1995a, 1995b, 1995c G. Antidiabetic Gunde-Cimerman, 1999 H. Other examples Usage in combination with other medicine 1. Physical exercise Alexeev & Kupin, 1993 2. Improving work capacity Mizuno, 1995a, 1995b, 1995c 3. Rapid recovery of normal physiology Mizuno, 1995a, 1995b, 1995c

Ref. Willard, 1990; Chen & Yu, 1993; Wasser, 2005a, 2005b

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The Royal sun, Agaricus safety measures for public health (Didukh response modifiers. Many other interesting brasiliensis modulates the immune et al, 2003). biological activities of lentinan are system against cancer. The active The schizophyllan derived from reported by various investigators (Hamada, substance and mechanism of their action Schizophyllum commune, shown to 1981; Aoki, 1984b; Hamuro & Chihara, is under way to be studied in detail. The activate macrophage in vitro and in vivo, 1985). hot water soluble fraction from which results in augmentation of T-cell The mushroom can lower blood A. brasiliensis fruit bodies’ significantly activities and increases sensitivity of pressure and free cholesterol in plasma, increased positive cells such as Pan T-cells, cytotoxic LAK and NK cells to Il-2 (Mizuno as well as accelerate the accumulation of helper T-cells, cytotoxic T-cells population et al, 1990). The laboratory tests seem lipids in the liver by removing them from (Mizuno et al, 1990a). The to indicate the role for the adrenalpituitary circulation. It helps in liver protection, polysaccharides from this mushroom is axis and central peripheral nervous system improves liver function and enhances the considered to be an effective prophylactic, including serotonin, 5HT, histamine and production of antibodies to hepatitis B. protecting humans against cancer by catecholamine in lentinans antitumour The 9g/day intake of dried Shiitake stimulating lymphocytes such as cytotoxic activity. mushroom decrease the serum T-cells, they are considered to be the active The lentinan from Lentinus cholesterol by 7-10% in patients suffering principles like polysaccharides present in edodes is also an important compound. from hypercholesterolaemia. The older boiled water extract. Another preparation It acts as the host defense potentiator and patients (60 years or more) with obtained with fine particles from fruit is able to store or augment the hyperlipidaemia have experienced a bodies (ABP-F) and from mycelium (ABP- responsiveness of host cells by stimulating decrease in total cholesterol levels by 9- M), prepared by mechanical disruption, maturation, differentiation, or 10% by taking 90g/day in 7 days. Lentinan activates the human complement system proliferation of cells involved in host has actively exerted an inhibitory activity in human serum via the alternative defense mechanisms (Chihara et al, on the HIV-1 reverse transcriptase and pathways, which depends on time and 1970). In one case the noble increase in proliferation of leukaemia cells. dose given. Thus, the extracts of fruit body several serum protein components in Mushroom products with their and mycelium and the culture broth α- and β- globulin regions is observed dose compensations for the cure of possess compounds exhibiting mainly in complement C3, hemopexin and respective disease are given in Table 3. antitumour, antiviral, antigenotoxic/ ceruloplasmin. The immunomodulating The lipid fractions isolated from antimutagenic and immunostimulatory action of mushroom polysaccharides is the fruiting bodies are highly effective activities. especially valuable as a prophylactic, a against Sarcoma 180 and highly Thirty seven species of 8 genera mild and non-invasive form of treatment, metastatic, drug resistant mouse Lewis out of 912 species belonging to 57 genera and in the prevention of metastatic Lung Carcinoma (LIC) cells via oral have been screened from family tumours, etc. administration. The active substance for obtaining biologically The immunoactive substance ergosterol is devoid of side effects that are active substances by cultivation. In view EP3, obtained from the fractionation of usually caused by cancer Chemotherapy of the rapidly growing popularity of Lentinus edodes mycelium is a lignin drugs. The ergosterol is an anti-angiogenic mushroom-based products, including complex (80%), 10% carbohydrates and substance. numerous products of species from family 10% protein. When lignin is removed from The water soluble extracts of Agaricaceae, the further elucidation of the above components the activity was Shiitake mushroom mycelium has shown active principles, mechanism of action, reduced. This means the activity was due antiviral and immunomodulating effects and their possible adverse effect as well to the water-soluble lignin containing and lentinan has shown various activities as the quest for other biological response numerous carboxyl groups. These host against various diseases, viz. antiviral modifiers by means of the screening defense potentiators (HDP’s) are activity in mice against VSV (vesicular programs was crucial in implementing functionally different from the biological somatitis virus), encephalitis virus,

Vol 4(4) July-August 2005 253 Review Article abelson virus, and adenovirus type 12. immunotherapy has been extracted from growing pure cultures of higher Stimulated nonspecific resistance against ‘Yung-Jong’, which belongs to the Basidiomycetes under controlled respiratory viral infections in mice, Ganodermataceae family. conditions on surfaces especially in enhanced bronchoalveolar, macrophage submerged cultures and the determination activity and increased resistance against Conclusion of optimal conditions of growth in the parasites Schistosoma japonicum submerged cultures are needed. The and S. mansoni. Lentinan has also exhibited The research reports mechanism of action of various secondary activity against Mycobacterium summarized in this article have highlighted metabolites isolated from medicinal and tuberculosis bacilli (resistant to the medicinal importance of mushrooms wild edible mushrooms is yet to be antituberculosis drugs), Bacillus subtilis, as new anticancer, anticholesterolenic, elucidated. Staphylococcus aureus, Micrococcus antidiabetic, hepatoprotective and lentius, Candida albicans and immunomodulative drug. However, the Acknowledgements Saccharomyces cerevisae. screening of mushrooms from different Ganoderma lucidum ecological and geographical regions of the We are grateful to the Honorable contains 800-2000 ppm of germanium, world is still required to identify, isolate, Dr. S.N. Patil, Vice-Chancellor, Amravati which can promote blood circulation, can design, develop, modify or prepare new University, Amravati, for valuable guidance increase the oxygen absorbing capacity of pharmacologically active compounds and for encouragement; and to Dr. S. K. the body and regulate the oxygen supply. from wild mushrooms. The development Deshmukh for supplying the literature. The medicine called PSK is used in cancer of a novel biotechnological process for

Table 3 : Mushroom products with their doses compensations for the cure of respective diseases

Mushroom Disease Dose Reference

Oral Administration

Trametes versicolor (PSK) Lung cancer 3 capsules 340 mg Tsang et al, 2003 three times daily Trametes versicolor (PSP) Immunosuppression 2g/kg/day Qian et al, 1997 Trametes versicolor (PSP) HIV-1 6.25 mg/ml Collins & Ng, 1997 Ganoderma lucidum (Ganopoly) Advanced cancer 600 mg three times daily Gao et al, 2002 Grifola frondosa D-fraction Various cancers 100 mg/day for 34 months Kodama et al, 2002

Intraperitoneal Administration

Sparassis crispa Cancer 250 µg/ mouse 1000 µg/ mouse Harada et al, 2002 Phellinus linteus Cancer 100 mg/kg of an acidic Kim et al, 2003 polysaccharide Agaricus brasiliensis Meth A tumour cells 10mg/kg/day × 30 Itoh et al, 1994 (F III-2-b and 5-FU)

PSP = polysaccharide peptide; PSK = Krestin Ganopoly = A crude polysaccharide fraction of Ganoderma lucidum

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References PG Gordon and Breach, Philadelphia, J Nat Prod, 1996, 59, 977-979. 1993, 297-394. 23. Daferner M, Anke T, Hellwig V, Steglich W 12. Berkeley Rev. MJ, Introduction to and Sterner O, Strobilurin M, 1. Alberts AW, MacDonald JS, Till AE and Cryptogamic Botany, London, H Bailliere, Tetrachloropyrocatechol and Tobert JA, Lovastatin, Cardiovasc Drug Food Ingred J (Japan), 1857, 167, 69-85. Tetrachloropyrocatechol methyl ether: new Rev, 1989, 7, 89-109. 13. Chang H and But P (Eds.), Lingzhi, antibiotics from Mycena species, 2. Alexeev V and Kupin V, Ganoderma Pharmacology and application of Chinese J Antibiot (Tokyo), 1998, 51, 816-822. lucidum administration in air- th materia medica, World Scientific 24. Dharmananda S, Medicinal Mushrooms, spacemedicine, 5 International Symposium publishing, Singapore, 1986, pp. 642-653. Best ways Magazine, July 1988, pp. 54-58. on Ganoderma lucidum, Seoul, 1993, 14. Chang R, Limitations and Potential 25. Didukh MY, Wasser SP and Eviatar N, pp. 60-63. applications of Ganoderma and related Medicinal value of species of the family 3. Anke T, Basidiomycetes: a source of new fungal polyglycans in clinical ontology; First Agaricaceae Cohn (Higher bioactive secondary metabolites, Prog Ind International Conference on Mushroom Basidiomycetes); Current Stage of Microbiol, 1989, 27, 51-66. Biology and Mushroom products, 1993, 96. knowledge and future perspectives, Int J 4. Anke T, Werle A, Bross M and Steglich W, 15. Chang R, Effective dose of Ganoderma in Med Mushr, 2003, 5, 133-152. Antibiotics from basidiomycetes XXXIII, humans, In: Proceedings Contributed 26. Ding G, Antiarrhythmia agents in Traditional Oudemansin X, a new antifungal E-β- Symposium 59A, B. 5th Int Mycol Congr, Chinese Medicines, Abstr Chin Med, Methoxyacrylate from Oudemansiella Buchanan PK, Hseu RS and Moncalvo JM 1987, 1, 287-308. radicata (Rehlan EX FR.) Sing, J (Eds), Taipei, 1994, pp.101-13. 27. Dufresne C, Young K, Pelaez F, Val AGD, Antibiot (Tokyo), 1990, 43(8), 16. Chang R, Functional properties of edible Valentino D, Graham A, Platas G, Bernard 1010-1011. mushrooms, Nutr Rev, 1996, 54(11), A and Zink D, Illudinic acid, a novel Illudane 5. Anke T, Werle A, Zapf S, Velten R and Steglich S91-S93. sesquiterpine antibiotic, J Nat Prod, W, Favolon, a new antifungal triterpenoid 17. Chen RY and Yu DQ, Studies on the 1997, 60, 188-190. from a Favolaschia species, J triterpenoid constituents of the spores from 28. Gao Y, Zhou S, Chen G, Dai X and Ye J, A Antibiot (Tokyo),1995, 48, 725-726. Ganoderma lucidum, Yao Hsueh phase I/II study of a Ganoderma 6. Aoki T, 1984a, Antibodies to HTLV I and Hsueh Pao (Acta Pharm Sinica), lucidum (Curt. Fr.)P. Karst. extract HTLV III in sera from two Japanese patients 1993, 26, 267-273. (Ganopoly) in patients with advanced one with possible pre-AIDS, Lancet, 1984, 18. Cheng HH, Hou WC and Lu ML, Interactions cancer, Int J Med Mushr, 2002, 4, 20, 936-937. of lipid metabolism and intestinal 207–214. 7. Aoki T, 1984b, Lentinan, In: Immune physiology with Tremella fuciformis 29. Gunde-Cimerman N, Medicinal value of the Modulating Agents and their Mechanisms, Berk. edible mushroom in rats fed a high- genus Pleurotus (Fr.) P. Krast (Agaricales RL Fenichel, and MA Chirgis (Eds), cholesterol diet with or without Nebacitin, S. R., Basidiomycetes), Int J Med Mushr, Immunol Studies, 1984, 25, 62-77. J Agric Food Chem, 1993, 50(25), 1999, 1, 69-80. 8. Arnone A, Cardillo R, Nasini G and Pava 7438-7443. 30. Hamada C, Inhibitory effect of lentinan on OVD, Cyathiformines A-D, new chorismate- 19. Chihara G, Antitumour and immunological the tumourigenesis of adenovirus type 12 derived metabolites from the fungus properties of polysaccharides from fungal in mice, In: Manipulation of Host Defense Clitocybe cyathiformis, Tetrahedron, origin, Mushr Sci, 1978, 9, 797-814. Mechanisms, Akoi, T et al (Eds.) 1993, 49, 7251- 7258. 20. Chihara G, Hamuro J, Maeda YY, Arai Y and Amsterdam, Excerpta Med Int Congr 9. Arnone A, Capelli S, Nasini G, Meille SV and Fukoeka F, Fractionation and purification Ser, 576, 1981, pp. 76-87. Pava OVD, Secondary mould metabolites II of the polysaccharides with marked 31. Hamuro J and Chihara G, Lentinan a T- cell Structure elucidation of diatretol - A new antitumour activity, especially lentinan from oriented immunopotentiator: Its Diketopiperzine metabolite from the fungus Lentinus edodes (Berk.) Sing (an edible experimental and clinical applications and Clitocybe diatreata, Liebigs Ann, mushroom), Cancer Res, 1970, 30, possible mechanism of immune 1996, 1875-1877. 2776 -2781. modulation, In: Fenichel R L, Chirigos M A 10. Bae EA, Kim DH and Han M J, Effect of 21. Collins RA and Ng TB, Polysaccharopeptide (Eds.), Immunomodulating agents and Lentinus edodes on the growth of from Coriolus versicolor has potential their mechanism of action. Dekker, New intestinal lactic acid bacteria, Arch Pharm for use against human immunodeficiency York, 1985, pp. 409-434. Res, 1997, 20, 443-447. virus type 1 infection, Life Sci, 1997, 32. Harada T, Miura N, Adachi Y, Nakajima M, 11. Buswell JA and Chang ST, Edible 60(25), 383-387. Yadomae T and Ohn N, Effect of SCG, 1, mushrooms, Attributes and applications. In 22. Cuellar MJ, Giner RM, Recio MC, Just MJ, 3-ß-D-glucan from on a Genetics and breeding of edible Manez S and Rios JL, Two Fungal lanostane the hematopoietic response in mushrooms Chang ST, Buswell, JA, Miles derivative as Phospholipase A2 Inhibitors, cyclophosphamide induced leukopenic

Vol 4(4) July-August 2005 255 Review Article

mice, Biol Pharm Bull, 2002, 25, Ganoderma: Systematics, Phytopathology Phellinus linteus (Berk. et Curt.) Teng 931–939. & Pharmacology: Proceedings of (Aphyllophoromycetedeae), Int J Med 33. Heim J, Anke T, Mocek U, Steffan B and Contributed Symposium 59 A, B. 5th Int Mushr, 2000, 2, 21-33. Steglich W, Antibiotics from Basidiomycetes Mycol Congr, 1994, Vancouver. 54. Mizuno T, Medicinal properties and clinical XXIX: Pilatin, A new antibiotically active 44. Kodama N, Komuta K and Nanba H, Can effects of Agaricus blazei Murill marasmane derivative from cultures of maitake MD-fraction aid cancer patients? (review), Int J Med Mushr, 2002, 4, Flagelloscypha pilatii Agerer., J Altern Med Rev, 2002, 7, 236-239. 299-313. Antibiot (Tokyo), 1988, 41, 1752-1757. 45. Kuschel A, Anke T, Velten R, Klostermeyer 55. Mizuno T, Kato L, Totsuka A, Shinkai K and 34. Hu B and But P, Chinese materia medica for D, Steglich W and Konig B, The Mniopetals, Shimizu M, Fractionation, structural features radiation protection, Abstr Chin Med, New Inhibitors of reverse transcriptases and antitumour activity of water soluble 1987, 1, 475-490. from a Mniopetalum species polysaccharide from “Reishi”: The Fruit body 35. Chem Abstr, 1992, 116, 160396. (Basidiomycetes), J Antibiot (Tokyo), of Ganoderma lucidum, Nippon Nogei 36. Ikekawa T, Enokitake Flammulina 1994, 47, 733-739. Kagaku Kaishi, 1984, 58, 871-880. velutipes: Antitumour activity of extracts 46. Lee IK, Jeong CY, Cho SM, Yun BS, KimYS, 56. Mizuno T, Hagiwara T, Nakamura T, Ito H, and polysaccharides, Food Rev Int, 1995, Yu SH, Koshino H and Yoo ID, Illudins C2 Shimura K, Sumiya T and Asakura A, 1990a, 11, 203-206. and C3, new illudin C derivates from Antitumour activity and some properties of 37. Ishikawa NK, Kasua M and Vanetti MC, Coprinus atramentarius AST20013, water soluble polysaccharides from Antibacterial activity of Lentinus edodes, J Antibiot (Tokyo), 1996, 49, 821-822. “Himematsutake” the fruiting body of grown in liquid medium, Braz J 47. Misaki A, Kakuta M, Sasaki T, Tanaka M and Agaricus blazei Murrill, Agric Biol Microbiol, 2001, 32, 206-210. Miyaji H, Studies on the interrelation of Chem, 1990, 54, 2889-2896. 38. Ikekawa T, Maruyama H, Miyano T, Okura structure and antitumour effects of 57. Mizuno T, Inagaki R, Kanao T, Hagiwara T, A, Sawasaki Y, Naito K, Kawamura K and polysaccharides: Antitumour action of Nakamura T, Ito H, Shimura K, Sumiya T Shiratori K, Proflamin a new antitumour periodate-modified, branched(1-3)-B-d- and Asakura A, 1990b, Antitumour activity agent: preparation, physicochemical Glucan of Auricularia auricula-judae and and some properties of water soluble properties and antitumour activity, Jpn J other polysaccharides containing (1-3)- hetero-glycans from “Himematsutake” the Cancer Res (Gann), 1985, 76, 142-148. Glycosidic Kikurages, Carbohydr Res, fruiting body of Agaricus blazei Murrill, 39. Itoh H, Ito H, Amano H and Noda H, 1981, 92,115-129. Agric Biol Chem, 1990, 54, 2897-2906. Inhibitory action of a (1>6)-beta-D-glucan- 48. Mizuno T, 1995a, Shiitake, Lentinus 58. Nanba H, Maitake mushroom — The king protein complex (F III-2-b) isolated from edodes: functional properties for of mushrooms, Mushr News, 1993, 41, Agaricus blazei Murill ("himematsutake") medicinal and food purposes, Food Rev 21-25. on Meth A fibrosarcoma-bearing mice and Int, 1995, 11(1), 111-128. 59. Ooi VEC and Liu F, A review of its antitumour mechanism, Jpn J 49. Mizuno T, 1995b, Bioactive biomolecules pharmacological activities of mushroom Pharmacol, 1994, 66(2), 265-271. of mushrooms: food function and medicinal polysaccharides, Int J Med Mushr, 1999, 40. Jeong H, Lee JW and Lee KH, Studies on effect of mushroom fungi, Food Rev Int, 3, 361-394. anticomplimentary activity of Korean 1995, 11(1), 7-21. 60. Qian ZM, Xu MF and Tang PL, higher fungi, Hanguk Kyunhakhoechi, 50. Mizuno T, 1995c, Kawariharatake, Polysaccharide peptide (PSP) restores 1990, 18, 145-148; Chem Abstr, 1991, Agaricus blazei Murrill: Medicinal and immunosuppression induced by 115, 218446. dietary effects, Food Rev Int, 1995, cyclophosphamide in rats, Am J Chin 41. Kawagishi H, Inagaki R, Kamao T, Mizuino 11(1), 167-172. Med, 1997, 25(1), 27-35. T, Shimura K, Ito H, Hagiwara T and 51. Mizuno T, Antitumour Mushrooms 61. Sakagami H and Aoki T, Induction of Nakamura T, Fractionation and antitumour Ganoderma lucidum, Grifola immuno potentiation activity by a protein- activity of the water-insoluble residue of frondosa, Lentinus edodes and bound polysaccharide, PSK (Review), Agaricus blazei fruiting body, Agaricus blazei, Gendai-shorin, Anticancer Res, 1991, 11, 993-1000. Carbohydr Res, 1989, 186, 267-273. Tokyo, 1997, 188p. 62. Sakagami H and Takeda M, Diverse 42. Kim GY, Roh SI, Park SK, Ahn SC, Oh YH, 52. Mizuno T, Immunological special diets, biological activity of PSK (Krestin), a protein Lee JD and Park YM, Alleviation of Agaricus blazei, Ganoderma bound polysaccharide from Coriolus experimental septic shock in mice by acidic lucidum, Cordyceps sinensis, versicolor. In:Mushroom Biology and polysaccharide isolated from the medicinal Grifola frondosa and Lentinus Mushroom Products. ST Chang, JA Buswell mushroom Phellinus linteus, Biol edodes, Gendai-shorin, Tokyo 1998, and SW Chiu (Eds), Chinese University Press, Pharm Bull, 2003, 26, 1418–1423. 188p. Hong Kong, 1993, pp. 237- 245. 43. Kim BK, Kim HW and Choi EC, Anti-HIV 53. Mizuno T, Development of an antitumour 63. Soo TS, The therapeutic value of effects of Ganoderma lucidum. In : biological response modifier from Ganoderma lucidum, 8th Int Mycol

256 Natural Product Radiance Review Article

Congr (IMC5), Abstracts, Vancouver, polysaccharides isolated from 83. Weber W, Anke T, Steffan B and Steglich W, B.C., 1994, pp. 95. Dictyophora indusiata, Ganoderma Antibiotics from Basidiomycetes XXXII 64. Soo TS, Effective Dosage of the extract of japonicum, Cordyceps cicadae, Strobilurin E: A New Cytostatic and Ganoderma lucidum in the Treatment Auricularia auricula- Judae and Antifungal (E)-Methoxyacrylate Antibiotic of Various Ailments, In: DJ Royse, (Ed), Auricularia Species, Chem Pharm from Crepidotus fulvotomentosus Mushroom Biology and Mushroom Bull, 1983, 31, 741-744. Peck, J Antibiot ( Tokyo), 1989, 43, Products. Proceedings of the Second 74. Ventura HO and Messerli FH, Abgiotensine 207-212. International Congress, 1996, pp. 177-186, converting enzyme inhibitors: a new class 84. Willard T, Reishi Mushroom: Herb of 65. Stadler M, Anke H and Sterner O, New of hypertensive drugs, In: Drugs therapy in Spiritual Potency and Medical Wonder, nematicidal and antimicrobial hypertension, JIM Drayer et al (Eds.), Sylvan Press, Washington, 1990, pp.110. compounds from the basidiomycete Marcel Deccer, Inc., 1987, pp. 139-161. 85. Yang QY and Wang MM, The effect of Cheimonophyllum candidissimum 75. Wasser SP, Dietary supplements from Ganoderma lucidum extract against (Berk and Curt) Sing, J Antibiot (Tokyo), medicinal mushrooms: Diversity of types fatigue and endurance in the absence of 1994, 47, 1284-1289. and variety of regulations, Int J Med oxygen. 5th International Mycological 66. Suzuki M, Higuchi S, Taki Y, Taki S, Miwa K Mushr, 2000, 2, 20-21. Congress (IMC5), Abstract, Vancouver, BC, and Hamuro J, Induction of endogenous 76. Wasser SP, 2005a, Reishi or Ling Zhi Canada, August, 14-21,1994, pp. 249. lymphokine-activated killer activity by (Ganoderma lucidum), In: 86. Ying J, Mao X, Ma Q, Zong Z and Wen H, combined administration of Lentinan and Encyclopedia of Dietary supplements, Icons of from China, X interleukin 2, Int J Immunopharmacol, Marcel Dekker, N.Y., 2005, pp. 603-620. Yuehan, (Ed), Science Press, Beijing, 1990, 12, 613-623. 77. Wasser SP, 2005b, Shiitake (Lentinus Translated. 67. Suzuki S and Oshima S, Influence of edodes), In: Encyclopedia of Dietary 87. Yoon SY, Eo SK, Kim YS, Lee CK and Han SS, Shiitake, Lentinus edodes, on human supplements, Marcel Dekker, N.Y., 2005, Antimicrobial activity of Ganoderma serum cholesterol, Ann Rep Natl Inst pp. 653-664. lucidum extract alone and in combination Nutr, 1974, 25, 89-94. 78. Wasser SP and Didukh MYA,Culinary- with some antibiotics, Arch Pharm 68. Suzuki S and Oshima S, Influence of shiitake, medicinal higher basidiomycete Res,1994, 17, 438-442. Lentinus edodes, on human serum mushrooms as a prominent source of 88. Zhuang C, Mizuno T, Shimada A, Ito H, cholesterol, Mushr Sci, 1976, 9(1), dietary supplements and drugs for the 21st Suzuki C, Mayuzumi Y, Okamoto H, MaY 463-467. century, Proceedings of the 5th International and Li J, Antitumour Protein-containing 69. Toth JO, Luu B, Beck J and Ourission G, Conference of Mushroom Biology and polysaccharides from a Chinese mushroom 1983a, Chemistry and biochemistry of Mushroom Products, Q Tan, J Zhang Fengweigu or Houbitake, Pleurotus oriental drugs, Part IX, Cytotoxic Triterpines MChen, HCao and JA(Eds), Buswell, sajor-caju (Fr.) Sing, Biosci Biotechnol from Ganoderma lucidum Sanghai, China, 2005, 12, 20-34. Biochem, 1993, 57, 901-906. (Polyporaceae): structures of ganoderic 79. Wasser SP and Weis AL 1997a, Shiitake 89. Zhuang C, Mizuno T, Ito H, Shimura K, acids U-Z, J Chem Res Synpo, 1983, mushroom [Lentinus edodes (berk.) Sumiya T and Kawade M, 1994a, 299;Chem Abstr,1984, 100, 117512. Sing.], In: E Nevo (Ed) Medicinal Fractionation and antitumour activity of 70. Toth JO, Luu B and Ourission G, 1983b, Les mushrooms, Peledfus, Haifa, Israel, 1997. polysaccharides from Grifola frondosa acides ganoderiques T a Z: Triterpenes 80. Wasser S P and Weis AL, 1997b, Reishi mycelium, Biosci Biotechnol Biochem, cytotoxiques de Ganoderma lucidum Mushroom [Ganoderma lucidum 1994, 58, 185-188. (Polyporaceae), Tetrahedron Lett, (Curt.: Fr.) P.Karst.]. In: E Nevo (Ed) 90. Zhuang C, Mizuno T, Ito H and Shimura K, 1983, 24, 1081-1084. Medicinal mushrooms. Peledfus, Haifa, 1994b,Chemical modifications and anti- 71. Tsang KW, Lam CL, Yan C, Mak JC, Ooi GC, Israel, 1997. tumour activity of polysaccharides from Ho JC, Lam B, Man R, Sham JS and Lam 81. Wasser SP and Weis AL, 1999a, Medicinal mycelium of liquid-cultured Grifola WK, Coriolus versicolor polysaccharide properties of substances occurring in frondosa, Nippon Shokuhin Kogyo peptide slows progression of advanced higher Basidiomycetes mushrooms: Gakkaishi,1994, 41, 733 -740. non-small cell lung cancer, Respir Med, current perspective, Int J Med Mushr, 2003, 97, 618–624. 1999, 1, 31-62. 72. Tsukagoshi S, Krestin (PSK), Cancer 82. Wasser SP and Weis AL, 1999b, Therapeutic Treatment Rev, 1984, 11, 131-155. effects of substances occurring in higher 73. Ukai S, Kiho T, Hara C, Morita M, Gao A and Basidiomycetes mushrooms: a modern Naomi HY, Polysaccharides in Fungi XIII perspective, Crit Rev Immunol, 1999, Antitumour activity of various 19, 65-96.

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