1.3. potential terapeutic ciup

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Therapeutic Potential of MushroomsMahendra Rai1*, Girish Tidke1 and Soloman P Wasser2

1Department of Biotechnology, Amravati University, Amravati – 444 602, Maharashtra, India2International Centre for Cryptogamic Plants and Fungi,

Institute of Evolution University of Haifa, Mt. Carmel, Haifa, 31905, Israel*Correspondent author, E-mail: pmkrai@hotmail.com

Received 15 April 2004; Revised 16 March 2005

Abstract

Mushrooms are an important natural source of foods and medicines. Traditionalaboriginals knew the medicinal importance of edible and wild mushrooms and these are nowbeing screened for their bioactivity in various ailments. Mushrooms represent a major and untappedsource of potent new pharmaceutical products. A wide range of activities including antitumour,cardiovascular and antimicrobial are reported in mushrooms. In developing countries like Indiamushroom progress is a boon in the field of food, medicine, and in generating employment. Thealternative systems of medicine utilize the curative properties of mushrooms. The present review isaimed to discuss biological activities of mushrooms and their roles in various human diseases.

Keywords: Mushrooms, Antimicrobial, Bioactivity, Biomedical, Cardiovascular, Therapeutics.

IPC code; Int. cl.7— A61K 35/84, A61P 9/00, A61P 31/00, A61P 35/00

Introduction

Mushrooms can be eitherhypogeous or epigeous, large enough tobe seen with the naked eye and usuallypicked by hands. They produce fleshy fruitbodies belonging to Basidiomycotina andAscomycotina. The edible nature ofmushrooms is now well-known. UsuallyAgaricus, Pleurotus and Volvariellaspp. are eaten all over the world ingeneral, and tropical countries, inparticular. However, the medicinaluses of the mushroom still need to beworked out for their biological activitiesdue to a fast increasing number ofmultidrug resistance in pathogenicmicrobes like Candida spp.,Staphylococcus aureus, S.epidermidis, Streptococcus spp.,Enterococcus spp. and Escherichia

coli (Ishikawa et al, 2001). The use ofmushrooms as medicine was mentionedby Berkeley (1857), whoreported that Calvatiagigantea (Giant Puffball)and C. caelata can be usedin burnt cases due to theiranaesthetic nature. Calvatiaspp. are also used to stopbleeding from wounds. Awood decaying fungus,Fomitopsis officinalis,which contains agaricin, isused in many medicines.

M u s h r o o m srepresent a major and as yet,largely untapped source ofpotent new pharmaceuticalproducts. Out ofapproximately 15,000 knownspecies, 2,000 are safe for

human consumption, and about 650 ofthese possess medicinal properties. In thesecond half of twentieth century, themushroom producing technologies havegrown enormously and the value of worldmushroom production was estimated tobe worth about eighteen billion US dollar.Many pharmaceutical substances withpotent and unique properties were recentlyextracted from mushrooms and make theirway all around the world. TheGanodermataceae family includesabout forty species with hard basidiocarp(fruit bodies). In Chinese folklore the fruitbody of Ganoderma lucidum (Fr.) P.

Agaricus sp.

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Karst. (Lingzhi) has been regarded as apanacea for all types of diseases likehepatopathy, chronic hepatitis, nephritis,hypertension, hyperlipidemic, arthritis,neurasthenia, insomnia, bronchitis,asthma, gastric ulcer, arteriosclerosis,leukopenia, diabetes and anorexia.

In developing countries like Indiamushrooms are a boon for progress inthe fields of food, medicine andunemployment. Mushrooms in thetwentieth century are well-known topeople all over the Asian countries as animportant bio-source of novel secondarymetabolites. In India, particularly thealternative systems of medicine, utilize thecurative properties of mushrooms. Thesecondary metabolites of thesemushrooms are chemically diverse andpossess a wide spectrum of biologicalactivities, which are explored in traditionalmedicines and in new targets of molecularbiology. They have important presentstatus and possess a potential to designfuture strategies for human health values.Pharmaceuticals worth $700 million USdollars are produced annually in Japanalone from Lentinus, Trametes,Schizophyllum, and Ganoderma.Extracts of various edible fungi, viz.Lentinus edodes, Flammulinavelutipes, Pleurotus ostreatus,

Agaricus bisporus, Pholiotanameko, Tricholoma matsutake andAuricularia auricula-judae possessantitumour effects also. In USA and JapanMaitake (Grifola frondosa) andShiitake (Lentinus edodes) have beenreported to be inhibitory to the AIDS virus.The important medicinal mushroomspecies with antitumour polysaccharidesin fruit bodies and cultured mycelium are:Tremella fuciformis, Schizophyllumcommune, Dendropolyporusumbellatus, Grifola frondosa,Hericium erinaceus, Inonotusobliquus, Ganoderma lucidum, G.applanatum, Lentinus edodes,Flammulina velutipes, etc. Theystimulate macrophage activity andstrengthen immune systems.

In traditional Chinese medicineextracts from many medicinal mushroomshave long been used for a wide range ofdiseases. Modern scientific and medicalstudies support many of these claims. Themain areas of medicinal studies includeanticancer, cholesterol and bloodpressure lowering, liver protective,antifibrotic, antiinflammatory, antidiabetic,and antimicrobial activity (Ooi & Liu,1999; Wasser & Weis, 1999a, 1999b;Gunde-Cimerman, 1999; Wasser, 2005 a,2005 b; Wasser & Didukh, 2005).

In addition to the therapeuticpotential, hundreds of the mushrooms arebeing explored the world over to study andreveal their biotechnological potential.Wasser (2002) has screened more thanone hundred Agaricales species fortheir antimicrobial and other suchproperties. The product made from themushroom is being sold in the nationaland international markets. They areavailable with prior clinical trials and

doses recommended by various doctorsand physicians.

The traditional uses of themushroom are known to the aboriginalsof Africa, India, Brazil and othercountries. In Nigeria, Puff balls(Lycoperdon pusilum and Calvatiagigantea) are used to cure sores,abrasion or bruises, deep cut,haemorrhages, and urinary infections(Buswell & Chang, 1993). In India,Ganoderma lucidum is used inasthma by the Baiga tribe of Central India,Agaricus spp. is used in goiter andLycoperdon pusilum in wound healingand also for controlling bleeding.

The medicinal and commercialpotential of bioactive substances derivedfrom higher Basidiomycetesmushrooms (edible and medicinal) andits proprietary biotechnology process inorder to produce new dietary supplementsand, at a later stage, new pharmaceuticalproducts, have been exploited. Extensivetests to obtain substances foranticancer, anticholesterol, antidiabetic,hepatoprotective and sexual potentialactivities have been performed in vitroand in vivo. Several dietary supplementsfrom fungal biomass are produced andtested. These supplements contain manybioactive substances with mild healthpromoting and sustaining effects. They donot specifically treat disease, rather, theyare used as functional food, on a dailybasis, strengthening and perfecting manydifferent physiological systems of thehuman body. Two new dietary supplementswith cholesterol lowering, antidiabetic andimmunostimulating properties have beenproduced and patented (Wasser, 2000).

The present review is aimed tosummarize the therapeutic importance of

Ganoderma sp.

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various mushrooms and explore furtherresearch in various areas and the futureprospects in order to develop a newgeneration of modern drugs.

Antitumour properties

The fruiting body of mushroomAgaricus brasiliensis S. Wasseret al (=blazei Murrill ss. Heinem)having a glycoprotein (50.2% sugar and43.3% protein) and three ergosterolderivatives (I, II, III), showed antitumouractivity. A β-D-glucan polysaccharideisolated from this mushroom alsoexhibited immunostimulative andantitumour activity (Mizuno et al, 1990;Kawagishi et al, 1989). However, a higherantitumour activity was observed inanother xyloglucan protein complexobtained from the 5% NaOH solution(Mizuno et al, 1990). A glycoproteinfraction obtained from A. campestrisalso exhibited antitumour activity againstSarcoma 180 in ICR mice; the proteinmoiety was composed of 17 amino acids(Jeong et al, 1990). Along withergosterol, six steroids are also isolatedfrom an acetone extract of A.brasiliensis fruit bodies. Out of the sixsteroids, three of them effectively inhibitedcell proliferation of cervical cancer cell(HeLa cells) (Mizuno, 2002). The acidicheteroglycans isolated from Auriculariaauricula-judae exhibited antitumouractivity on implanted Sarcoma 180 (Ukaiet al, 1983; Misaki et al, 1981).

Extracts of fruiting bodies ofBoletus edulis have shown 100%inhibition against Sarcoma 180 and 90%inhibition against Ehrlich carcinoma inmice (Ying et al, 1987). Calvacin wasisolated from Calvatia gigantea with

antitumour activity. Flammulinavelutipes, exhibits strong antitumouractivity against Sarcoma 180, Lewis cancerof lung, and B-16 melanoma (Ikekawa,1995). The antitumour glycoproteinproflamin found in mycelia of F.velutipes is effective against allogeneicand syngeneic tumours by oraladministration. Proflamin augmentsantibody formation and activateslymphocyte blastogenesis (Ikekawa, 1995;Ikekawa et al, 1985). A polysaccharide,PA3 DE, isolated from this fungus has alsoshown inhibitory activity against implantedSarcoma 180 (solid tumour) in mice.

The triterpenoids isolated fromGanoderma lucidum are C3 epimersand C-3/C -15 positional isomers in pairs.A β-D-glucan isolated from this fungusshowed immunostimulative antitumouractivity. A glycoprotein fraction GL isolatedfrom the hot water soluble componentsof the basidiocarp of G. lucidum showed81% inhibition of tumour growth in mice.GL exerted the antitumour activity throughimmunopotentiation and not throughdirect cytotoxicity against the tumours.(Chem Abstr, 1992). From the culturemycelium of G. lucidum, Toth et al(1983a, 1983b) isolated ganoderic acidsZ, Y, X, W, V and U which were found to becytotoxic to hepatoma cells in vitro.Glucuronoglucan, xyloglucan, mannoglucan,xylomannoglucan and other activeheteroglucans and their potentialcomplexes, extracted from this specieswere purified using salts, alkali and DMSO(Mizuno et al, 1984; Willard, 1990;Wasser & Weis, 1997b).

A protein with β-glucan isolatedfrom Grifola frondosa extract exhibitsantitumour activity by potentiating anti-tumour cellular functions by directly

enhancing various mediators such aslymphokines and IL-1 (Nanba, 1993).Grifolan (β-glucan), xyloglucan,annoglucan, fucomannoglucan,compounds isolated from this funguspossess antitumour property (Mizuno,1997, 1998). Heteroglucan protein,mannogalactofucan, heteroxylan,galactomannoglucan, compounds isolatedfrom submerged cultures of G. frondosahave also shown antitumour activity(Zhuang et al, 1994a, 1994b). Theantitumour properties of Lentinusedodes are attributed to thepolysaccharide lentinan and emitanin.Lentinan is now used as an antitumourdrug (Chihara et al, 1970). Lentinan isnontoxic to tumour cells, but inhibitstumour growth by stimulating the immunesystem (Chihara, 1978).

The mushroom Pleurotussajor-caju contains protein havingpolysaccharide xyloglucan, xylanproteins,has showna n t i t u m o u ractivity againstSarcoma 180tumour cells invivo (Zhuanget al, 1993).T r a m e t e s( C o r i o l u s )versicolor wasfound to possessantitumour andimmunostimulantp r o p e r t i e s .From thecarpophores ofthis fungus, a polysaccharide fraction, builtup of glucose (96.44%), xylose (2.16%) andmannose (1.73%), exhibiting antitumouractivity was isolated. PSP, a glycopeptide

Pleurotus sajor-caju

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possessing antitumour andimmunostimulant activities was alsoobtained from the ethanol extract of T.versicolor mycelium (Yang & Wang,1994).

Cardiovascular andhypercholesterolemicproperties

Lentinus edodes can lowerboth blood pressure and free cholesterolin plasma, as well as accelerateaccumulation of lipids in liver byremoving them from circulation. In mostdeveloped countries, the common causeof death is coronary artery disease. Themain risk factors are hypercholesteromiaand dislipoproteinemia, diabetes,disturbance in blood platelet binding andhigh blood pressure. The initial steps forthe prevention and treatment of CAD andhypercholesterolemia are the modificationin regime with a diet low in fats andsaturated fatty acids in crude fibers.Clinical intervention studies have clearlydemonstrated therapeutic importance ofcorrecting hypercholesterolemia (Albertet al,1989).

Mevinolin is producedcommercially from the filamentousfungus Aspergillus tereus. This is thefirst specific inhibitor of microzomalenzyme that occurs early in thebiosynthetic pathway to cholesterolformation. The addition of 4% driedPleurotus to a high cholesterol dietreduced cholesterol accumulation in theserum effectively and liver of experimentalrats. Cholesterol lowering effect of themushroom Pleurotus ostreatus inhypercholesterolemic rats is also reported.It has been suggested that Pleurotus

mushrooms could be recommended as anatural cholesterol lowering substancewithin the human diet (Gunde-Cimerman,1999).

In western countries coronaryartery disease is the major cause of death,while hypercholesterolemia is a riskfactor, which causes the hardening of thearteries. In humans, 50% or more of totalcholesterol I is derived from de novosynthesis. It has been proven that Shiitakemushroom is used to lower blood serumcholesterol (BSC) via a factor known aseritadenine, which is also called“Lentinacin” or “Lyntisine”. It is knownthat, apparently, eritadenine reduces BSCin mice, not by inhibition of cholesterolbiosynthesis, but by the acceleration ofexcretion of ingested cholesterol and itsmetabolic decomposition (Suzuki &Oshima, 1974, 1976). Eritadenine alsolower the blood levels of cholesterol andlipids in animals.

Antimicrobial properties

In recent years Basidiomycetesand other higher fungi including somerecognized medicinal mushrooms havebeen re-investigated as sources of novelantibiotics mainly as a result of increasingdifficulty and the cost of isolating novelbioactive compounds from the

Actinomycetes and Streptomycetes.The water extract of Lentinus

edodes demonstrated growth-enhancing effects on colon inhabitingbeneficial lactic acid bacteria,Lactobacillus brevis andBifidobacteria brevie. The effectivefactor in the extract is considered tobe the disaccharide sugar, trehalose.The L. edodes extract can improve thebeneficial intestinal flora of the gut andreduced harmful effects of certainbacterial enzymes such asβ-glucosidase, β-glucorinidase andtryptophase as well as reducing coloncancer formation (Bae, 1997). It isclear from the results that mushroomsalso have antimicrobial properties.

The bioactive compounds likemniopetals, oudemansin, lanostane andstrobilurin possess potent antimicrobialactivity (Table 1). Their dosecompensation and the mode of action issubject for research for new generationresearchers. Clearly, the antimicrobialpotential of extract of several medicinalmushroom type and indeed otherBasidiomycetes not yet exploited, mustwarrant further examination.

The heavy molecular weight cellwall polysaccharides, for example, PSPfrom Trametes versicolor inhibitsLentinus edodes

Lentinus edodes

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Table 1 : Compounds showing antimicrobial activity

Mushrooms Bioactive compounds Bioactivity Reference

Cheimonophylum Cheimonophyllon A-E Antibacterial, Stadler et al, 1994candissimum weak antifungal

Clitocybe cyathiformis Cyathiformine A Antibacterial and Arnone et al, 1993antifungal

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, 1998Tetrachloropyrocatechol 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, 1996inhibitor (group ofantiinflammatory agents)

growth of infectious yeast, such asCandida albicans (Tsukagoshi, 1984;Sakagami, 1991, 1993). Antitumourpolysaccharides inhibit bacteria such asBacillus subtilis, Staphylococcusaureus, Escherichia coli andPseudomonas aeruginosa.Hericium erinaceus shows strongantimicrobial activity against a broadrange of infectious agents. Compoundsextracted from Agaricus bisporus,

Lentinus edodes, Coprinuscomatus and Oudemansiellamucida have been reported to haveantifungal and antibacterial properties.

Clinical trials and other usesof mushrooms

Clinical trials were conducted on56 cancer patients, 30 were chosen toreceive the medicinal mushroom extract

mix and another 26 comparable patientsreceiving the accepted pharmaceuticaldrug Polyactin-A as a control group. Allpatients were in the middle-late stages(stage 3 and 4) of cancer. The experimentconcludes that the tablets of mixedpolysaccharides, made up of the six speciesof medicinal mushrooms, can become anew health product to improve immunitywith high effectiveness and nontoxicity.However, further trials are needed.

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The polysaccharides extracted fromAgaricus brasiliensis, Grifolafrondosa, Lentinus edodes,Ganoderma lucidum, Trametesversicolor and Cordyceps sinensisare used to produce tablets for inhibitingthe growth of tumours and improving theimmunity.

The products of Ganodermalucidum are prescribed in various forms;it can be injected as a solution ofpowdered spores or given as syrup. It canbe taken as tea, soup, capsules, tinctures,or bolus. In tincture form, the dose givenis 10 ml thrice daily. In case of syrup thedose is 4-6 ml/day. The dried mushroom(200-300 g) is prepared in water and givenas a drink, the recommended dose is 3-5times daily (Ying et al, 1987; Zhuang,1993).

In Japan, Ganodermalucidum is used for the treatment of thecancer (Willard, 1990). The resultsobtained after application shows that thepatient sleeps well with a healthier feelingand has an increased appetite; Reishi alsoprovides relief from angina pectoris.Injection of spore powder is effective incuring progressive deterioration, atrophyand muscles stiffness. The effect ofelevation changes has been prevented andcured by tablets of mushroom spores.

In an experimental study fortherapeutic application of G. lucidum,143 patients with advanced previouslytreated cancer were given an oral G.lucidum polysaccharide extract of 1800mg three times daily for 12 weeks. Twenty-seven patients were not assessable forresponse and toxicity, because they wereunable to track for follow-up or refusedfurther therapy before the 12 weeks oftreatment were up. Of the 100 fully

assessable patients, 46 (32.2%) hadprogressive disease before or at the sixweeks evaluation point (range: 5 days-6weeks). There was no significant changein the Functional Assessment of CancerTherapy-General (FACT-G) scores in 85assessable patients. In the group withstable disease, FACT-G scores improved in23 patients, remained unchanged in five,and declined in one. Within this group,the median change from the baselinescore to the 6 and 12 weeks was +7.6and +10.3, both statistically significant(P < 0.05). For the 38 patients with SD,the median change from the baselinescore was 28.1 ± 10.2 weeks. Thisindicates that Ganopoly may have anadjunct role in the treatment of patientswith advanced cancer although objectiveresponses were not observed in the study(Wasser & Weis, 1997a).

G. lucidum and othermushrooms like G. applanatum,Lentinus edodes, Flammulinavelutipes, Grifola frondosa fromChina, Korea, Japan and India have beenused in many clinical studies with animalsand humans, reporting the beneficialresults. The high-molecular-weightpolysaccharides from the cell walls ofG. lucidum are physiologically active.They are used against various diseases likediabetes, Alzheimer’s disease, retinalpigmentary degeneration, atrophicmyotonous hepatodymia, rhinitis,leucopoenia, insomnia, dyspnea,neurasthenia and duodenal ulcers. Thewater extract from fruit body hadinhibitory activity on histamine releasefrom rat peritoneal mast cells, induced bycompound 48/80 or antigen-antibodyreaction and on passive cutaneousanaphylaxis reaction in guinea pigs and

the rats. This activity is due to theGanoderic acids C and D, which are alsoresponsible for the treatment of asthmaand allergy. The polysaccharides andtriterpenoids have also shown the anti- HIVactivity. They also show protective effectson liver in animal and human studies(Wasser & Weis, 1997b).

Ganopoly is well-tolerated andappears to be active against HBV patientswith chronic hepatitis B. The mechanismfor hepatoprotective effects ofG. lucidum have been largely undefined.However, accumulating evidence suggestsseveral possible mechanisms, whichinclude antioxidants and radicalscavenging activity, modulation of hepaticPhase I and II enzymes inhibition ofβ-glucuronidase, antifibrotic and antiviralactivity, modulation of NO production,maintenance of hepatocellular calciumhomeostasis and immunomodulatingeffects. G. lucidum also cures lung andheart dysfunction. Clinical studies on thiswere conducted in China in which 200patients with chronic bronchitis weregiven G. lucidum in tablet form and60-90% patients showed markedimprovement with increased appetite. Italso reduced blood and plasma viscosityin hypertensive patients withhyperlipidaemia. The extracts of thismushroom were reported to reduce bloodcholesterol and blood pressure and alsotreat arrhythmia (Ding, 1987; Chenget al, 1993). G. lucidum has also shownhypoglycaemic and hypolipidemicactivities. In a study, 71 patients withconfirmed type II diabetes mellitus werecured and had best results. This studydemonstrated that Ganopoly is efficaciousand safe in lowering blood glucoseconcentrations.

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The practitioner experiencesalong with preliminary clinical reportsindicate that immunostimulatingpolysaccharides of G. lucidum are useful

in treating certain viral diseases, inducingHIV and Epstein Barr Virus (EBV), thecause of mononucleosis. The G. lucidumis one of the ingredients in skin lotions

produced for protection against UVradiation. (Ying et al, 1987). Currentbiomedical applications ofG. lucidum are given in Table 2.

Table 2 : Current biomedical applications of Ganoderma lucidum

Applications References

A. Immunomodulating effects Chang, 19941. Anticancer Mizuno, 1995a, 1995b, 1995c2. Antiviral (e.g., anti-HIV) Kim et al, 19943. Antibacterial Yoon et al, 19944. Therapy of auto-immune disorders Chang, 1993, 1994, 1996B. Cardiovascular disorders1. Coronary dilation and increasing coronary circulation Soo, 1994, 19962. Anti-hyperlipidemic, and antiplatelet hypoglycaemic Chang & But, 1986

aggregation (blood clots)C. Cancer therapy1. Maintain leucocyte count Chang, 1994; Soo, 19942. Enhance the immune system Soo, 19963. Reduction of chemotherapy toxicity and elimination of Chang & But, 1986; Hu & But, 1987; Chen & Yu, 1993;

induced leucopenia (low blood leucocytes) Mizuno, 1995 a, 1995 b, 1995 cby chemotherapy

4. Remission to prevent relapses Chang, 1994D. Remission of cancer and hepatitis B treatment Ventura & Messerli, 1987; Chang, 1993;

Mizuno, 1995a, 1995b, 1995cE. Enhancing oxygen utilization1. Relief of discomfort of high altitude stress, headaches, Dharmananda, 1988

dizziness, nausea & insomnia2. Relief of oxygen deprivation caused by coronary Mizuno, 1995c

arteries blocked by atheromas, spasms or clotsF. Anti-ageing, anti-oxidant free radical scavengers Mizuno, 1995a, 1995b, 1995cG. Antidiabetic Gunde-Cimerman, 1999H. Other examplesUsage in combination with other medicine1. Physical exercise Alexeev & Kupin, 19932. Improving work capacity Mizuno, 1995a, 1995b, 1995c3. 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, Agaricusbrasiliensis modulates the immunesystem against cancer. The activesubstance and mechanism of their actionis under way to be studied in detail. Thehot water soluble fraction fromA. brasiliensis fruit bodies’ significantlyincreased positive cells such as Pan T-cells,helper T-cells, cytotoxic T-cells population(Mizuno et al, 1990a). Thepolysaccharides from this mushroom isconsidered to be an effective prophylactic,protecting humans against cancer bystimulating lymphocytes such as cytotoxicT-cells, they are considered to be the activeprinciples like polysaccharides present inboiled water extract. Another preparationobtained with fine particles from fruitbodies (ABP-F) and from mycelium (ABP-M), prepared by mechanical disruption,activates the human complement systemin human serum via the alternativepathways, which depends on time anddose given. Thus, the extracts of fruit bodyand mycelium and the culture brothpossess compounds exhibitingantitumour, antiviral, antigenotoxic/antimutagenic and immunostimulatoryactivities.

Thirty seven species of 8 generaout of 912 species belonging to 57 generahave been screened from familyAgaricaceae for obtaining biologicallyactive substances by cultivation. In viewof the rapidly growing popularity ofmushroom-based products, includingnumerous products of species from familyAgaricaceae, the further elucidation ofactive principles, mechanism of action,and their possible adverse effect as wellas the quest for other biological responsemodifiers by means of the screeningprograms was crucial in implementing

safety measures for public health (Didukhet al, 2003).

The schizophyllan derived fromSchizophyllum commune, shown toactivate macrophage in vitro and in vivo,which results in augmentation of T-cellactivities and increases sensitivity ofcytotoxic LAK and NK cells to Il-2 (Mizunoet al, 1990). The laboratory tests seemto indicate the role for the adrenalpituitaryaxis and central peripheral nervous systemincluding serotonin, 5HT, histamine andcatecholamine in lentinans antitumouractivity.

The lentinan from Lentinusedodes is also an important compound.It acts as the host defense potentiator andis able to store or augment theresponsiveness of host cells by stimulatingmaturation, differentiation, orproliferation of cells involved in hostdefense mechanisms (Chihara et al,1970). In one case the noble increase inseveral serum protein components inα- and β- globulin regions is observedmainly in complement C3, hemopexin andceruloplasmin. The immunomodulatingaction of mushroom polysaccharides isespecially valuable as a prophylactic, amild and non-invasive form of treatment,and in the prevention of metastatictumours, etc.

The immunoactive substanceEP3, obtained from the fractionation ofLentinus edodes mycelium is a lignincomplex (80%), 10% carbohydrates and10% protein. When lignin is removed fromthe above components the activity wasreduced. This means the activity was dueto the water-soluble lignin containingnumerous carboxyl groups. These hostdefense potentiators (HDP’s) arefunctionally different from the biological

response modifiers. Many other interestingbiological activities of lentinan arereported by various investigators (Hamada,1981; Aoki, 1984b; Hamuro & Chihara,1985).

The mushroom can lower bloodpressure and free cholesterol in plasma,as well as accelerate the accumulation oflipids in the liver by removing them fromcirculation. It helps in liver protection,improves liver function and enhances theproduction of antibodies to hepatitis B.The 9g/day intake of dried Shiitakemushroom decrease the serumcholesterol by 7-10% in patients sufferingfrom hypercholesterolaemia. The olderpatients (60 years or more) withhyperlipidaemia have experienced adecrease in total cholesterol levels by 9-10% by taking 90g/day in 7 days. Lentinanhas actively exerted an inhibitory activityon the HIV-1 reverse transcriptase andproliferation of leukaemia cells.

Mushroom products with theirdose compensations for the cure ofrespective disease are given in Table 3.

The lipid fractions isolated fromthe fruiting bodies are highly effectiveagainst Sarcoma 180 and highlymetastatic, drug resistant mouse LewisLung Carcinoma (LIC) cells via oraladministration. The active substanceergosterol is devoid of side effects that areusually caused by cancer Chemotherapydrugs. The ergosterol is an anti-angiogenicsubstance.

The water soluble extracts ofShiitake mushroom mycelium has shownantiviral and immunomodulating effectsand lentinan has shown various activitiesagainst various diseases, viz. antiviralactivity in mice against VSV (vesicularsomatitis virus), encephalitis virus,

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abelson virus, and adenovirus type 12.Stimulated nonspecific resistance againstrespiratory viral infections in mice,enhanced bronchoalveolar, macrophageactivity and increased resistance againstthe parasites Schistosoma japonicumand S. mansoni. Lentinan has also exhibitedactivity against Mycobacteriumtuberculosis bacilli (resistant toantituberculosis drugs), Bacillus subtilis,Staphylococcus aureus, Micrococcuslentius, Candida albicans andSaccharomyces cerevisae.

Ganoderma lucidumcontains 800-2000 ppm of germanium,which can promote blood circulation, canincrease the oxygen absorbing capacity ofthe body and regulate the oxygen supply.The medicine called PSK is used in cancer

immunotherapy has been extracted from‘Yung-Jong’, which belongs to theGanodermataceae family.

Conclusion

The research reportssummarized in this article have highlightedthe medicinal importance of mushroomsas new anticancer, anticholesterolenic,antidiabetic, hepatoprotective andimmunomodulative drug. However, thescreening of mushrooms from differentecological and geographical regions of theworld is still required to identify, isolate,design, develop, modify or prepare newpharmacologically active compoundsfrom wild mushrooms. The developmentof a novel biotechnological process for

growing pure cultures of higherBasidiomycetes under controlledconditions on surfaces especially insubmerged cultures and the determinationof optimal conditions of growth insubmerged cultures are needed. Themechanism of action of various secondarymetabolites isolated from medicinal andwild edible mushrooms is yet to beelucidated.

Acknowledgements

We are grateful to the HonorableDr. S.N. Patil, Vice-Chancellor, AmravatiUniversity, Amravati, for valuable guidanceand for encouragement; and to Dr. S. K.Deshmukh for supplying the literature.

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 dailyTrametes 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, 2002Grifola 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, 2002Phellinus 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 = KrestinGanopoly = A crude polysaccharide fraction of Ganoderma lucidum

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