Potential to Develop Functional Food Products from Mushroom Bioactive Compounds

Journal of Hygienic Engineering and Design

Review paper UDC 615.322:635.82.012

POTENTIAL TO DEVELOP FUNCTIONAL FOOD PRODUCTS FROM MUSHROOM BIOACTIVE COMPOUNDS

Mark Shamtsyan1*

1Saint Petersburg State Institute of Technology (Technical University), Moskovsky prospect 26, 198013 St. Petersburg, Russia

*e-mail: [email protected]

Abstract From prehistoric times mushrooms have been used Bioactive substances of mushroom origin with im- not only for nutrition but also for healing purposes. mune modulating, antioxidant and antibacterial prop- At present there are already several hundred species erties can be used as functional and anti-microbial of mushrooms for which there are known various ther- food and animal feed supplements. As functional food apeutic properties, and which can be used as dietary supplements mushroom derived substances with hy- supplements or for fortification of food with functional pocholesterolic, hypolipidemic, hepatoprotective, an- compounds. tidiabetic, and some other activities can be used, while alcohol dehydrogenase could be used for wine and In vitro and in vivo studies on immune modulating, an- beer production, milk-clotting enzymes can find utili- titumor, hypocholesterolic, hypolipidemic, antidiabet- zation in cheese making to substitute animal rennin. ic and other effects were performed. Enzymatic activities were studied using appropriate substrates. Mushrooms are not a special taxonomic group, but include about 14,000 species which form fruit-bodies, Immune-modulating effect of rich with beta-glucans seen by the naked eye. They are greatly evaluated for mushroom extracts was demonstrated. It was shown, their nutritional value and many are viewed as func- that studied extracts also have antitumor effect. Hy- tional foods. pocholesterolic, hypolipidemic, antidiabetic, milk-clotting, and other effects of uptake of mushroom extracts Mushrooms are good source of proteins. The protein were clearly shown. content in mushrooms is much higher than in most vegetables and somewhat less than in meat and milk. Besides well-known immune modulating and an- They contain all essential amino acids, but the con- ti-tumor effects, mushrooms possess other valuable tent of methionine and cysteine can be not sufficient. properties including antioxidant, anti-hypertensive, Mushrooms are rich in dietary fiber, and therefore, cal- cholesterol-lowering, liver protection, anti-obesity, an- orific value of most of them is not high. They are also a ti-inflammatory, anti-diabetic, anti-microbial and some good source of vitamins. Definitely, edible mushrooms others. Mushrooms also can be a source of various en- represent a nutritious and tasteful source of food and zymes useful for food industry. can be important dietary component for vegetarians. Key words: Mushrooms, Bioactive components, Immune Centuries ago people recognized that mushrooms modulators, Antimicrobial hypocholesterolic, Antidiabetic, could have significant health benefits. The most of tra- Hepatoprotective, Antioxidant activity, Milk-clotting. ditional information on mushrooms beneficial bioactive properties comes from the Far East Asia. Historically, mushrooms were collected from the wild 1. Introduction for eating and for medicinal use. China has been the Mushrooms contain a large variety of bioactive com- cradle of many of mushrooms early cultivations, since pounds that are greatly under researched. Possible 600 AD (Auricularia auricular - the "Jelly ear"). White contribution of mushrooms to different fields, includ- button mushroom (Agaricus bisporus) was first culti- ing prospects of their use in food industry, are consid- vated in France in 17th century while Oyster mushroom erably untapped.

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(Pleurotus ostreatus) was first grown in US in early 20th 2.1 Immune modulating and anti-tumor effect century. While mushroom cultivation now spans many The main anti-tumor compounds currently isolated centuries, it is only over the last five decades that there from mushrooms have been identified as either water have been major expansions in basic research and soluble β-D-glucans, β-D-glucans with heterosaccha- practical knowledge leading to the formation of a ma- ride chains of xylose, mannose, galactose or uronic jor global industry. In the second half of 20th century acid or β-D-glucan-protein complexes – proteogly- technologies for mushroom cultivation were strongly cans, which can induce immune modulatory and ther- developed, and at the beginning of 21st century the apeutic effect in animals and humans. overall value of the world’s mushroom production was estimated to be over $ 45 billion [1]. The main chain of basic β-D-glucan is either β 1-3, β 1-4 or mixed β 1-3, β 1-4 with β 1-6 side chains of differ- An even more promising technique of mushroom ent sizes occurring at various intervals [9]. Levels of ac- production is submerged cultivation of their mycelia, tivity of these compounds can be related to their size, which is a more efficient way to attain the biomass of degree of branching, molecular weight and solubility basidiomycetes. Mushroom mycelia possess almost in water. Some of this compounds, referred to as bio- same valuable properties as the fruit bodies. Native logical response modifiers. liquid of mushroom cultivation could be a valuable source of extracellular enzymes, vitamins, polysaccha- These mushroom substances are able to influence rides and other important substances and could be non-specific and specific immune responses of an -or used as a source of various bioactive compounds. ganism and activate different types of immune com- petent cells, such as: monocytes, neutrophils, cytotoxic macrophages, natural killer cells, dendritic cells, cyto- 2. Mushrooms bioactive compounds kins, interferons, and lymphocytes. At the present, there are more hundreds of mushroom Immune stimulation during cancer can be beneficial in species for whom variety of bioactive properties are terms of tumor regression and patients’ survival [10]. detected. Currently, on the world pharmaceutical and Results published by Kodama N. et al., propose a mech- food markets large amount arsenal of mushroom prod- anism of action a low-molecular-weight protein frac- ucts and compounds exist, representing so called “nu- tion from the fruiting body of the maitake mushroom triceutics” or “functional food additives”. When used for Grifola frondosa in which natural killer cells (NK cells) a curative means, mushrooms are normally consumed are activated through cytokines produced by anti- as powdered concentrates or extracts in hot water. The gen-presenting cells [11]. extracts can be used as a drink, freeze-dried, or spray- dried to form granular powders, which allow for easier Ganoderma. lucidum modulates the immune system, handling, packaging, transportation and consump- including, for example, antigen-presenting cells, NK tion [2]. These liquid concentrates or dried powdered cells, and the T and B lymphocytes. It also promoted mushroom extracts can be placed in capsule and then phagocytosis by macrophage from peripheral blood can be considered as dietary supplements or mush- mononuclear cell (PBMC) and it also promoted natural room nutriceuticals with potential health benefits [3]. killer cell activity. It decreased the percentage of leu- And many of these bioactive substances can be used kemia cells in the spleens of mice before they were in- to fortify common food products to provide them jected with WEHI-3 cells. Apparently, G. lucidum affects functional properties. murine leukemia WEHI-3 cells in vivo [12]. While there is a great deal of attention focused on the Research, performed in City of Hope National Medical various immunological and anti-cancer properties of Center and Beckman Research Institute, Duarte Cali- mushrooms [2, 4], they can also offer other potential- fornia in USA, proposes that addition of one serving of ly important therapeutic properties including antiox- white button mushrooms (Agaricus bisporus) a day to idants, anti-hypertensive, cholesterol-lowering, liver the diet of men with previously diagnosed with pros- protection, anti-inflammatory, anti-diabetic, anti-viral, tate cancer can decrease PSA levels, a key indicator of anti-microbial and others [5 - 8]. Cross index of most tumor growth [13]. studied mushrooms and their bioactive properties is Oral administration of mushroom extracts were signifi- presented in the Table 1. cantly increasing the survival rates of mice with very x - Commercially developed mushroom product malignant tumors of Melanoma-B16 and Ehrikhs ascid carcinoma [14]. + - Non-commercially developed mushroom product Studies of underlying mechanisms of mushrooms will continue to help in devising new strategies for treat- ing cancer, preventing its long-term problems, and increasing survival [15].

52 Journal of Hygienic Engineering and Design

2.2 Cardiovascular and cholesterol-lowering effect of antibodies to hepatitis B (2). There have been other interesting medical reports concerning to distinct im- Hypercholesterolemia increases the risk of cardiovas- provement with patients suffering from cirrhosis of the cular diseases and is among the major risk factors for liver and chronic hepatitis B with extracts or polysac- human health in developed countries. Elevated levels charides from Dendropolyprus umbellatus, Schizophyl- of circulating cholesterol cause deposits to form inside lum commune, Trametes versicolor, Poria cocos, Tremella blood vessels. These deposits can result in a disease fuciformis and others. process called arteriosclerosis. Metabolic syndrome, which comprises a cluster of Cholesterol has been divided into two major catego- metabolic abnormalities, such as hyperlipidemia, dia- ries: low-density lipoprotein (LDL) and very low-den- betes mellitus, and hypertension, is a widespread and sity lipoprotein (VLDL), the so-called “bad” cholester- increasingly prevalent disease in industrialized coun- ol, and high-density lipoprotein (HDL), the so-called tries and contributes to the increase in cardiovascular “good” cholesterol. morbidity and mortality [19, 20]. Nonalcoholic fatty The first steps in the prevention and treatment of hy- liver disease (NAFLD) is often associated with features percholesterolemia and associated cardiovascular dis- of metabolic syndrome and is emerging as the most eases is the development of the dietary regime with common liver disease worldwide [21, 22]. Research a food low in fats and saturated fatty acids and rich in conducted by Japanese scientists showed that Muki- crude fibers. Mushrooms, due to their high fiber con- take mushroom (Panellus serotinus) supplementation tent and low calorific value, are proper for diets de- is beneficial for the alleviation of NAFLD and dyslipid- signed to prevent cardiovascular diseases. emia in obese, diabetic ob/ob mice [23]. Being rich in dietary fiber, some mushrooms also can produce ingredients, inhibiting cholesterol syntheses. 2.4 Anti-diabetic effect A major rate-limiting step in the biosynthetic pathway Extracts of several higher fungi, including: Tremella au- for cholesterol formation is at the level of the microso- rantia, Cordyceps sinensis, G. lucidum, Auricularia auricu- mal enzyme 3-hydroxy-3-methylglutaryl-coenzymeA la-judae, L. edodes, Pleurotus ostreatus, Phellinus linteus reductase (HMG-CoA reductase) that catalyses the re- and others have been shown to decrease blood glucose ductions of HMG-CoA into mevalonate. and triglyceride levels. Such results strongly suggest Some species from the genus of Pleurotus are capable that these mushrooms have potential preventive and to produce mevinolin (lovastatin), which was the first therapeutic action in diabetes mellitus (type I and II). specific inhibitor of the HMG-CoA reductase to obtain Antidiabetic activity of Grifola frondosa is related to the approval for the treatment of hypocholesteremia. process of metabolism of adsorbed glucose. The blood Eritadenine, a compound extracted from Lentinus edo- glucose lowering effect is thought to be a result of a des is also able to lower blood serum cholesterol. Prob- high molecular weight glycoprotein. ably, eritadenine lowers cholesterol by decreasing the The consumption of P. ostreatus produced a significant ratio of phosphatidylcholine to phosphatidylethanol- hypoglycemic action in diabetic mice [24] and it is ca- amine in liver microsomes. pable of improving hyperlipidemia and the impaired [ ] The addition of dried fruit bodies or submerge mycel- kidney functions in alloxan-induced diabetic mice 25 . lium of some other mushrooms to a high cholesterol Ethanolic extract of P. ostreatus showed a significant diet effectively reduced cholesterol accumulation in decrease in serum glucose level. Thus, indicating that the serum and liver of experimental rats redistribut- the ethanolic extract of P. ostreatus could be added in ing cholesterol in favor of HLDL, reduced production the list of medicinal preparations beneficial in diabetes of VLDL and LDL cholesterol, reduced cholesterol ab- mellitus [25]. sorption and reduced HMG-CoA reductase activity in In other study Ganoderma lucidum extract exhibit- the liver and triglyceride level in blood serum [16 - 18]. ed good dose-dependent inhibitory activity against α-glycosidase with and also exhibited aldose reduc- 2.3 Hepatoprotective effects tase inhibitory potential. Tremella fuciformis demon- Mushrooms are considered to be beneficial for a wide strated high aldose reductase inhibitory activity [26]. range of hepatic disorders, including hepatitis. Several substances isolated fruit body, mycelia and spores of 2.5 Anti-obesity effects G. lucidum, such as, ganoderic acids, ganosporeric acid Obesity is currently associated with low-grade chron- A were shown to have strong antihepatotoxic activity. ic inflammation and intestinal dysbacteriosis. It was A polysaccharide fraction from L. edodes demonstrat- shown, that a water extract of G. lucidum mycelium ed liver protective action in animals together with reduces body weight, inflammation and insulin resis- improved liver function and an increased production tance in mice fed a high-fat diet [27].

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Table 1. Cross Index of Most Studied Higher Basidiomycetes and Their Bioactive Properties BIOLOGICAL ACTIVITY

Taxa Immunomodulating Antitumour Antiobesity and Antiparasitic Antibacterial Anti-inflammatory regulation Blood pressure Hypercholesterolemia disorders, Cardiovascular Antidiabetic tonic Kidney Hepatoprotective Nerve tonic potentiator Sexual bronchitis Chronic Antioxidant Milk clotting dehydrogenase Alcohol Hydrophobins Auriculariales Auricularia auricula-judas (Bull.) Wettst + + + x x Tremellales Tremella fuciformis Berk. + + + + + + x Tremella mesenterica Rits.: Fr. + + + +

Polyporales Albatrellus ovinus + + + (Schaeff.) Kotl. & Pouzar Cerrena unicolor (Bull.) Murrill. + + + + Daedaleopsis confragosa + + + (Bolton) J. Schröt Dendropolyporus umbelatus x x x x (Pers. Fr.) J l. Dendropolyporus umbelatus x x x x (Pers. Fr.) J l. Fomes fomentarius (L.) J.J. Kickx + + + + Fomitopsis pinicola (Schw.:Fr.) P. Karst. + + + + + Grifola frondosa (Dicks. Fr.) S.F. Gray x x + x x x x + x + + Hericium erinaceum (bull.:Fr.) Pers. x + x x x x Irpex lacteus (Fr.) Fr. + x Laetiporus sulphureus (Bull.) Murrill + + Piptopurus betulinus (bull.:Fr.) P. Karst + + + Piptoporus soloniensis + (Dubois : Fries) Pilat Polyporus squamosus (Huds.) Fr. + Poria cocos (Schw.) Wolf x x + Schyzophyllum commune Fr.:Fr. x x x x x x + + Sparassis crispa (Wulfen) Fr. + Trametes versicolor (L.:Fr.) Lloyd x x x x x Trametes ochracea + + (Pers.) Gilb. & Ryvarden Trichapatum laricinum + (P. Karst) Ryvarden Ganodermatales Ganoderma lucidum (Curt.:Fr.) P. Karst x x + x x x x x x x x x x + GANODERMA APPLANATUM (PERS.) PAT. + + + Hymenochaetales Inonotus obliquus (Ach. ex Pers.) Pilat x x x Aphillophorales Phellinus linteus (L.ex Fr) Quel x x Phellinus robustus + (P.Karst.) Bond. et Singer

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Agaricales Pleurotacea Lentinus edodes (Berk.) Sing x x + x x x x x x x + Pleurotus cornucopiae + + + (Pau. Ex Pers.) Rollan Pleurotus cystidiosus Luis + Pleurotus dryinus (Pers.) P.Kumm + Pleurotus ostreatus (Jack.:Fr.) Kumm x + + + + + + + + + + Pleurotus pulmonarius (Fr.:Fr.) Quel + Pleurotus nebrodensis (Inzegna) Quél. + Mycenaceae Panellus serotinus (Pers.) Kühner + + Tricholomataceae Armillariella mellea (Vafl.:Fr.) P. Karst. x x x + Armillaria ostoyae (Romagn.) Herink + Clitocybe nuda (Bull.) + H.E.Bigelow & A.H.Sm. Flamulina velutipes (Curt.:Fr.) P.Karst. x x + x + + + Hypsizigus marmoreus (Peck) Bigel x Lepista personata (Fr.) Cooke + Marasmius androsaceus (L.:Fr.) Fr. x x Tricholoma matsutake + (S.Ito et S.Imai) Singer Agaricaceae Agaricus blazei Murr. x x + Agaricus bisporus (J. Lge) Imbach x + + x x + + Agaricus campestris L. + Chlorophyllum rhacodes (Vittad.) Vellinga + Coprinus comatus (O.F. Müll.) Persoon + + Coprinus domesticus (Bolton:Fr.) Grey + + Coprinus lagopides P. Karst. + + Coprinellus micaceus (Bull.) Vilgalys + + + Boletaceae Boletus edulis Bull. + Boletus erythropus Pers. + Leccinum scabrum (Bull.) Gray + Neoboletus pseudosulphureus + (Kallenb.) W. Klofac Amanitaceae Amanita rubescens (Pers. ex Fr.) Gray + Lepiotaceae Macrolepiota procera (Scop.) Singer + Suillaceae Suillus luteus (L.) Roussel + Pluteaceae Volvariela volvacea (Bull.:Fr.) Sing. + + + + Hydnaceae Hydnum repandum L. + Russulaceae Lactarius deliciosus (L. ex Fr.) S. F.Gray + Lactifluus piperatus (L.) Roussel + Lactarius salmonicolor R. Heim & Leclair + Lactifluus volemus (Fr.) Kuntze + Russula delica Fr. + Russula integra (L.) Fr. + Russula nigricans (Bull.) Fr. + Russula vinosa Lindblad + Bolbitaceae Agrocybe aegerita (Brit.) Sing + + + Strophariaceae Pholiota adiposa (Batsch) P. Kumm. + + + + Pholiota nameko (T. Ito)S. Ito & Imai + + Hypocreales Cordyceps sinensis (Berk) Succ. x x x x x x x x x

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Obtained results indicate that G. lucidum and its high infections [4]. Lentinan, commercial β-D-glucan prepa- molecular weight polysaccharides may be used as pre- ration from L. edodes, has shown antiviral activity in biotic agents to prevent gut dysbacteriosis and obesi- mice against vesicular Stomatis virus, Encephalitis vi- ty-related metabolic disorders in obese individuals [27]. rus, Abelson virus, an Adenovirus type 12, stimulated non-specific resistance against respiratory viral infec- Anti-obesity and triglyceride lowering effect has been tion in mice, conferred complete protection against an reported for fermented milk product containing edible LD75 challenge dose of virulent mouse influenza A/ mushroom water extracts (mushroom yogurt) [28]. SW15, increased resistance to the protozoal parasites, The anti-obesity activity of Maitake mushroom (G. exhibited activity against Mycobacterium tuberculosis frondosa) has been demonstrated in both animals and bacilli resistant to anti-tuberculosis drugs, Bacillus sub- humans [29]. tilis, Staphylococcus aureus, Micrococcus lenteus, Can- A group of Korean scientists studied the anti-obesity dida albicans and Saccharomyces cerevisiae, increased properties of L. edodes water extract powder in mice host resistance to infections with potentially lethal fed a high fat diet. Consumption of high fat diet caused Listeria monocytogenes [16]. increases in body weight, serum lipid profiles, and ad- Sulfated Schizophyllan polysaccharide (Schizophyllum ipose tissue weights. Serum total cholesterol and total commune) displayed strong anti-HIV activity while the triglyceride levels for the animals from mushroom ex- anti-tumour effect was reduced or lost. Schizophyllan tract powder-supplemented groups were lower than has also been reported to enhance protection against those in the control group. Supplementation with Staphylococcus sp. infection. 5% mushroom extract considerably suppressed body weight gain and reduced the weight of subcutaneous Extensive examination of over 200 species of Basidio- adipose tissue compared to the high fat diet group. mycetes in Spain demonstrated that almost 50% had High fat diet ingestion resulted in higher lipid content significant direct antibiotic activity against a range of and increased lipid peroxidation in the liver. However, test organisms. It is interesting to note that the brack- L. edodes water extract powder supplementation in- et polypore Piptoporus betulinus carried by the histor- hibited accumulation of hepatic lipids induced by high ic Iceman displayed a high broad spectrum antibiotic fat diet, considerably decreased malondialdehyde lev- activity. els, and elevated total antioxidant activity in the liv- L. edodes extracts can improve the beneficial intesti- ers of mice. Histopathological analysis indicated that nal flora of the gut, the effective factor in the extract is the livers of mice fed high fat diet developed hepatic considered to be the trehalose, and reduce the harmful steatosis, whereas mushroom extract-treated groups effects of certain bacterial enzymes such as α-gluco- showed small fat droplets. These results suggest that sidase, α-glucuronidase and tryptophanase as well as long-term supplementation with L. edodes water ex- reducing colon cancer formation [16]. tract powder may also have an ameliorating effect on high fat diet-induced obesity [30]. 2.7 Antioxidant activity Anti-obesity effect of polysaccharides in the water-sol- Antioxidants play a very important role in protecting uble fraction from edible mushroom Hinmogi (Tremella the body from the formation of free radicals. Therefore, fuciformis) demonstrated inhibitory effects on 3T3-L1 it becomes very important for many to supplement adipocyte differentiation, peroxisome proliferators-ac- their diet with compounds rich of antioxidants. tivated receptor γ translation in 3T3-L1 cells was. In addition, treatment of polysacharides to 3T3-L1 cells sig- It was shown that mushroom extracts and polysaccha- nificantly inhibited the triglyceride accumulation, Oil rides can decrease the production of oxygen free rad- Red-O staining, and mRNA expression of PPARγ, C/EBP icals. Significant superoxide and hydroxyl radical scav- α, and leptin in a dose-dependent manner. Based upon enging activities have been demonstrated for several these results, it is possible to resume, that studied poly- mushroom antitumour polysaccharides [16]. Metha- saccharides can be used as a potential anti-obesity ma- nolic extracts of various edible mushrooms also show terial [31]. various kinds of antioxidant activities [32]. Recent studies of Serbian scientists show, that Agaricus 2.6 Antimicrobial effects species can be a source of antioxidant, antimicrobial Various antitumor polysaccharides from medicinal and antiquorum sensing compounds [33]. mushrooms would be expected to function by mobi- lizing the body’s humoral immunity to protect from vi- 2.8 Nerve tonic activity ral, bacterial, fungal and protozoal infections resistant Nerve growth factors (NGF) called Erinacins (series to current antibiotics. of diterpenoids) and hericenones (a class of benzyl Several mushroom polysaccharides have shown antivi- alcohol) were isolated from the fruit bodies, myce- ral activity against Ectromelia virus and Cytomegalovirus lia and culture broth of Hericium erinaceum and were

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stimulating nerve growth factor synthesis. The erinac- the fungus Schizophyllum commune special proteins ines are the most powerful inducers of NGF synthesis were found, which later were called hydrophobins. The among all currently identified natural compounds. name hydrophobins has been assigned to a family of small secreted and moderately hydrophobic fungal 2.9 Enzymes useful in food industry proteins with a characteristic spacing of eight cysteine residues. These proteins possess unique physical prop- Higher mushrooms can represent an interest for the erties and can find application in various fields [43]. food industry, not only as a source of biologically active Hydrophobins self-assemble into amphipathic mem- supplements, but also as a source of useful enzymes. branes, converting the properties of contact surfac- Milk clotting enzymes from higher basidiomycetes are a es. One of the most promising applications of hydro- promising source to substitute rennin in cheese making. phobins is their use as stabilizers for edible foams and emulsions [44]. Emulsions of these proteins by their The quality of cheese significantly depends from en- taste and mouth feel resemble fats and can be used zyme preparations which are used for milk clotting. not only as natural highly efficient stabilizers, but also Mostly animal enzymes extracted from rennet are used to replace fats from emulated products, thus allowing for these purposes. Requirements for the substitutes to create novel dietetic foods. of the rennet are strict and specific - their enzymatic properties must maximally approach those of accept- ed as the standard natural rennin, i.e. together with the high milk-clotting activity they must possess the insig- 3. Conclusions nificant general proteolytic activity, which leads to the - Mushrooms are a promising source for the food in- unspecific proteolysis of the proteins of casein. dustry, but their full potential is not yet unlocked. Highly active proteases of rennet action are discovered - Their possibilities and utilization are tremendous, es- in the higher basidiomycetes and some of them found pecially, for those products taken from submerge culti- practical use. vation of higher mushrooms as bioactive or functional In 1970th Japanese scientists Kawai M. and Mukai N. food supplements and as a source of valuable enzymes reported, that Irpex lacteus and Flamulina velutipes and proteins. mushrooms could be a promising rennet substitute for cheese-making [34]. In later studies these results were confirmed by other researchers [35, 36]. 4. References A peptidase from another mushroom, Piptoporus soloni- [1] Chang S. T. (2006). The World Mushroom Industry: Trends and Technological Development. 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