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November 1996: (ll)S91S93 Functional Properties of Edible Mushrooms Raymond Chang, M.D., F.A.C.P. Commonly known mushrooms that are both edible and have functional properties include Auricularia (mu-er), Flammulina (enokitake), Grifola (maitake), Hericium, Lentinus (shiitake), Pleurotus (oyster), and Tremella (yin- er). Most edible mushrooms, however, do not have me- dicinal value (e.g., Agaricus bisporus), and some medici- nal mushrooms (e.g. Ganoderma, Coriolus) are not ed- ible. Of the =10,000 known species of mushrooms, it is currently thought that =700 are edible and >200 may have medicinal value, although only a small percentage of these mushrooms are available to the consumer.' Although many cultures have used mushrooms as both food and medicine, the use of mushrooms as a functional food is most notable in the East, where application of mushrooms to maintain health was formally recorded as early as 100 AD in China. Mushrooms have been incor- porated into health tonics, tinctures, teas, soups, and health- ful food dishes, as well as herbal formulas. Within the framework of traditional medicine, mushrooms have been appliedto lubricate the lungs (Tremella fuciformis), tonify the kidneys (Cordyceps sinensis), reduce excessive damp- ness (Grifola umbellate), and invigorate the spleen (Poria COCOS). More recently, functional mushrooms have been shown to modulate the immune system, lower blood pres- sure and blood lipid concentrations, and inhibit tumors, inflammation, and microbialaction. I will discussthe shiitake (Lentinusedodes) as a model of the functional mushrooms with demonstrated bioactivity because it is widely con- sumed as a food in the East and increasingly in the West, and extensive research on its bioactivity has led to the iso- lation of pure compounds that have reached pharmaceuti- cal status. Shiitake as a Model for Functional Mushrooms Shiitake is the common Japanese name for Lentinus edodes, and is also the common name now used in the West. Indigenous to Asia, shiitake is now cultivated and Dr. Chang is Associate Attending Physician and Assistant Professor, Department of Medicine, Memorial Sloan-Kettering Cancer Center and Cornell Medical College, New York, USA. is the second most commonly produced edible mushroom in the world? Besides being a culinary delicacy, there is a long tradition of use of shiitake as medicine in Asia, dat- ing back >2000 years. Shiitake contains protein (26% of dry eight)^; lipids (primarily linoleic acid); carbohydrate; fiber; minerals; vitamins B-I, B-2, and C; and ergosterol: the D provita- min. Besides its nutritive content, several important com- pounds have been isolated from shiitakethat have immuno- modulatory, lipid-lowering, and antimicrobial properties. These include lentinan, Lentinus edodes mycelium (LEM), KS-2, and eritadenine. Of these, lentinan is the most stud- ied. In 1969, Ikekawa et al.5 noted that a water extract of shiitake fruiting bodies could inhibit transplanted tumors in mice. Around the same time, Chihara et isolated an antitumor polysaccharide from shiitake and named it lentinan. The molecular formula for lentinan is (C,H,oO,)n, and the mean molecular mass is 500 kDa. Lentinan is a p- D-glucan as shown by electrophoresis, ultracentrifugation, and other instrumental analyses. Its structure was con- firmed as p-( 1,3)-D-gIucopyranan with a branched chain of p-( 1,6)-monoglycosyl, showing a right-handed triple helix.',* Lentinan has been found to activate macrophages, T lymphocytes, and other immune effector cells that modu- late the release of cytokines, which may in turn account for its indirect antitumor and antimicrobial proper tie^.^ The antitumor effects of lentinan are believed to be a result of immunopotentiation, which has been demon- strated in allogeneic, syngeneic, and autologous rodent tumor test systems and confirmed in randomized, con- trolled clinical trials in humans.I0For example, Taguchi" reported significant improvement (p < 0.01) in survival in patients with advanced gastric cancer who were treated with lentinan and chemotherapy compared with those treated with chemotherapy alone. The antimicrobial ef- fects of lentinan are also believed to be enacted via immu- nologic potentiation of host defenses, which has been dem- onstrated against bacterial, viral, and parasitic infections.'* Other biologically active polysaccharide fractions have also been isolated from shiitake. LEM is derived from shiitake mycelium and contains a heteroglycan protein Nutrition Reviews, Vol. 54, No. 11 s9 1

Functional Properties of Edible Mushrooms

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Page 1: Functional Properties of Edible Mushrooms

November 1996: (ll)S91S93

Functional Properties of Edible Mushrooms Raymond Chang, M.D., F.A.C.P.

Commonly known mushrooms that are both edible and have functional properties include Auricularia (mu-er), Flammulina (enokitake), Grifola (maitake), Hericium, Lentinus (shiitake), Pleurotus (oyster), and Tremella (yin- er). Most edible mushrooms, however, do not have me- dicinal value (e.g., Agaricus bisporus), and some medici- nal mushrooms (e.g. Ganoderma, Coriolus) are not ed- ible. Of the =10,000 known species of mushrooms, it is currently thought that =700 are edible and >200 may have medicinal value, although only a small percentage of these mushrooms are available to the consumer.'

Although many cultures have used mushrooms as both food and medicine, the use of mushrooms as a functional food is most notable in the East, where application of mushrooms to maintain health was formally recorded as early as 100 AD in China. Mushrooms have been incor- porated into health tonics, tinctures, teas, soups, and health- ful food dishes, as well as herbal formulas. Within the framework of traditional medicine, mushrooms have been applied to lubricate the lungs (Tremella fuciformis), tonify the kidneys (Cordyceps sinensis), reduce excessive damp- ness (Grifola umbellate), and invigorate the spleen (Poria COCOS). More recently, functional mushrooms have been shown to modulate the immune system, lower blood pres- sure and blood lipid concentrations, and inhibit tumors, inflammation, and microbial action. I will discuss the shiitake (Lentinus edodes) as a model of the functional mushrooms with demonstrated bioactivity because it is widely con- sumed as a food in the East and increasingly in the West, and extensive research on its bioactivity has led to the iso- lation of pure compounds that have reached pharmaceuti- cal status.

Shiitake as a Model for Functional Mushrooms

Shiitake is the common Japanese name for Lentinus edodes, and is also the common name now used in the West. Indigenous to Asia, shiitake is now cultivated and

Dr. Chang is Associate Attending Physician and Assistant Professor, Department of Medicine, Memorial Sloan-Kettering Cancer Center and Cornell Medical College, New York, USA.

is the second most commonly produced edible mushroom in the world? Besides being a culinary delicacy, there is a long tradition of use of shiitake as medicine in Asia, dat- ing back >2000 years.

Shiitake contains protein (26% of dry eight)^; lipids (primarily linoleic acid); carbohydrate; fiber; minerals; vitamins B-I, B-2, and C; and ergosterol: the D provita- min. Besides its nutritive content, several important com- pounds have been isolated from shiitake that have immuno- modulatory, lipid-lowering, and antimicrobial properties. These include lentinan, Lentinus edodes mycelium (LEM), KS-2, and eritadenine. Of these, lentinan is the most stud- ied.

In 1969, Ikekawa et al.5 noted that a water extract of shiitake fruiting bodies could inhibit transplanted tumors in mice. Around the same time, Chihara et isolated an antitumor polysaccharide from shiitake and named it lentinan. The molecular formula for lentinan is (C,H,oO,)n, and the mean molecular mass is 500 kDa. Lentinan is a p- D-glucan as shown by electrophoresis, ultracentrifugation, and other instrumental analyses. Its structure was con- firmed as p-( 1,3)-D-gIucopyranan with a branched chain of p-( 1,6)-monoglycosyl, showing a right-handed triple helix.',* Lentinan has been found to activate macrophages, T lymphocytes, and other immune effector cells that modu- late the release of cytokines, which may in turn account for its indirect antitumor and antimicrobial proper tie^.^

The antitumor effects of lentinan are believed to be a result of immunopotentiation, which has been demon- strated in allogeneic, syngeneic, and autologous rodent tumor test systems and confirmed in randomized, con- trolled clinical trials in humans.I0 For example, Taguchi" reported significant improvement (p < 0.01) in survival in patients with advanced gastric cancer who were treated with lentinan and chemotherapy compared with those treated with chemotherapy alone. The antimicrobial ef- fects of lentinan are also believed to be enacted via immu- nologic potentiation of host defenses, which has been dem- onstrated against bacterial, viral, and parasitic infections.'*

Other biologically active polysaccharide fractions have also been isolated from shiitake. LEM is derived from shiitake mycelium and contains a heteroglycan protein

Nutrition Reviews, Vol. 54, No. 11 s9 1

Page 2: Functional Properties of Edible Mushrooms

conjugate as its major active ~0nstituent.l~ It is active orally, and has been studied mostly for its antiviral properties. In a clinical trial of40 patients with chronic hepatitis B, LEM improved liver function and reduced viremia.I4 More in- terestingly, LEM,has been shown to inhibit human immu- nodeficiency virus (HIV) infection in vitroI5 and may have promise as a therapy for acquired immunodeficiency syn- drome. Another compound isolated from shiitake is eritadenine, which has been shown to lower serum cho- lesterol and lipid concentrations in various studies in ro- dent~ .~~, ' ' Besides the well-studied compounds just dis- cussed, other potentially beneficial compounds have been found in shiitake. One example is thioproline, which blocks the formation of carcinogenic N-nitroso compounds.18

A purified compound is very different from the whole mushroom, however, and the inevitable questions that fol- low are whether eating the whole mushroom has preven- tive or therapeutic value, and if so, how much mushroom should be consumed and in what form. For shiitake, re- searchers found that the powdered mushroom h i t bodies given to rats as 1 &20% of their diet inhibited transplanted t u m ~ r s , ~ ~ J ~ and small studies have demonstrated lipid-low- ering effects of consumption of 9 g of dried mushrooms or 90 g of fresh mushrooms.21

The content and potency of bioactive ingredients may differ depending on how the mushroom is prepared and ingested. For example, the anticarcinogenic thioproline content varies from undetectable amounts in fresh shiitake, to 134 mg/100 g of dried shiitake, to 843 mg/100 g of boiled shiitake.I8 As is the case for most plants and herbs, the specific strain, growing conditions, and other environ- mental factors will also significantly affect the taste, form, and substance of the mushroom, as well as affect the bioactive content.22

Summary

Edible mushrooms such as shiitake may have important salutary effects on health or even in treating disease. A mushroom characteristically contains many different bio- active compounds with diverse biological activity, and the content and bioactivity of these compounds depend on how the mushroom is prepared and consumed. It is esti- mated that 4 0 % of the annual 5 million metric tons of cultivated edible mushrooms contain fknctional "nutra- ceutical" or medicinal properties.2 In order of decreasing cultivated tonnage, Lentinus (shiitake), Pleurotus (oys- ter), Auricularia (mu-er), Flammulina (enokitake), Tremella (yin-er) , Hericium, and Grifola (maitake) mushrooms have various degrees of immunomodulatory, lipid-lowering, an- titumor, and other beneficial or therapeutic health effects without any significant toxicity.

Although the data for this functional food class are not as strong as those for other functional foods such as cruciferous vegetables, because of their potential useful-

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ness in preventing or treating serious health conditions such as cancer, acquired immune deficiency syndrome (AIDS), and hypercholesterolemia, functional mushrooms deserve fkrther serious investigation. Additionally, there is a need for epidemiological evidence of the role of this functional food class.

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Kendrick B. The Fifth Kingdom. Waterloo: Mycologue Publication, 1985 Chang ST. Mushroom biology: the impact on mush- room production and mushroom products. In: Chang ST, Buswell JA, Chiu SW, eds. Mushroom Biology and Mushroom Products. Hong Kong: Chinese University Press, 19933-20 Terashita T, Kono M, Mishima N, Obata T, Yamauchi M. The proximate components, free and protein-bound amino acids in protein and 5'GMP in fruit-bodies of Lentinus edodesSinger Shiitake mushroom grown on artificial bed-blocks. J Jpn SOC Food Sci Techno1 1990;37:52W2 Ying J, Mao X, Ma Q, Zong Y, Wen H. Icons of me- dicinal fungi from China. Beijing: Science Press, 1987 lkekawa T, Uehara N, Maeda Y, Nankinishi M, Fukuoka F. Antitumor activity of aqueous extracts of edible mushrooms. Cancer Res 1969;29:734-5 Chihara G, Hamuro J, Maeda Y, Arai Y, Fukuoka F. Fractionation and purification of the polysaccharides with marked antitumor activity, especially Lentinan, from Lentinus edodes (Berk.), Sing., an edible mush- room. Cancer Res 1970;30:2776-81 Sasaki T, and Takasuka N. Further study of the struc- ture of lentinan, an antitumor polysaccharide from Lentinus edodes. Carbohydr Res 1976;47:9%104 Bluhm TL, Sarco A. The triple helical structure of lentinan, a P-(l-3)-D-glucan. Can J Chem 1977; 55:293-9 Hamuro J, Chihara G. Lentinan, a T-cell oriented immunopotentiator: its experimental and clinical ap- plications and possible mechanism of immune modu- lation. In: Fenichel RL, Chirigos MA, eds. Immune Modulation Agents and Their Mechanisms. New York: Marcel Dekker, 1985:409-36 Chihara G, Hamuro J, Maeda Y, et al. Antitumor and metastasis inhibitory activities of lentinan as an immunomodulator. Cancer Detect Prev 1987;(Suppl 1 ):423-43 Taguchi T. Clinical efficacy of lentinan on patients with stomach cancer: end-point results of a four-year fol- low-up survey. Cancer Detect Prev 1987;(suppl 1 ):333-49 Kaneko Y, Chihara G. Potentiation of host resistance against microbial infections by lentinan and its related polysaccharides. In: Friedman H, ed. Microbial I n k - tions. New York: Plenum, 1992:201-15 Sugano N, Hibino Y, Choji Y, Maeda H. Anticar- cinogenic actions of water-soluble and alcohol-in- soluble fractions from culture medium of Lentinus edodes mycelia. Cancer Lett 19823 7:l 0%14 Amagasse H. Treatment of heaptitis B patients with Lentinus edodes mycelia. In: New Trends in Peptic Ulcer and Chronic Hepatitis. Part II. Chronic Hepati- tis. Princeton: Exerpta Medica 1987;31621

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15. Tochikura T, Nakashima H, Ohashi Y, Yamamoto N. Inhibition (in vitro) of replication and of the cytopathic effect of human immunodeficiency virus by an extract of the culture medium of Lentinus edodes mycelia. Med Microbiol lmmunol 1988;177:235-44

16. Yamamura Y, Cochran KW. Chronic hypocholes- terolemic effect of Lentinus edodes in mice and ab- sence of effect on scrapie. Science 1974;9:489-93

17. Chibata I, Okumura K, Takeyama S, Kotera K. Lentin- acin: a new hypocholesterolemic substance in Lentin- us edodes. Specialia Experentia 1969;25:1237-8

18. Kurashima Y, Tsuda M, Sugimura T. Marked forma- tion of thiazolidine-4-carboxylic acid, an effective ni- trite trapping agent in vivo, on boiling of dried shiitake mushroom (Lentinus edodes). J Agric Food Chem 1990;38:194!5-9

19. Nanba H. Antitumor action of Shiitake (Lentinus edodes)fruit bodies orally administered to mice. Chem Pharm Bull 1987;35:2459-6

20. Mori K, Toyomasu T, Nanba H, Kuroda H. Antitumor activities of edible mushrooms by oral administration. In: Wuest PJ, Royse DJ, Beelman RB, eds. Proceed- ings of the International Symposium on Scientific and Technical Aspects of Cultivating Edible Fungi. Amsterdam: Elsevier, 19873-6

21. Susuki S, Oshima S. Influence of Shi-Ta-Ke (Lentinus edodes) on human serum cholesterol. Mushroom Sci 1976;9(Part 1):46%7

22. Royse DJ, Bahler CC. Effects of genotype, spawn run time and substrate formulation on biological efficiency of shitake. Appl Environ Microbiol 1996;52:1425-7

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