Review of Medicinal Mushrooms Advances: Good News from Old Allies]

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2002;56:28-33 © American Botanical Council

 

 

Review of Medicinal Mushrooms Advances: Good News from Old Allies

 

by Solomon P. Wasser, Ph.D., Dr.Sci. (Biol.)

 

Edible and medicinal mushrooms (macrofungi) not only can convert the

huge lignocellulosic biomass* waste into human food, but -- most

remarkably -- can produce notable mycopharmaceuticals,

myconutriceuticals and mycocosmeceuticals.

 

The most significant aspect of mushroom cultivation, if managed

properly, is to create zero emission of lignocellulosic waste materials.

Mushroom biotechnological products have multibeneficial effects to human

welfare (e.g., as food, health tonics and medicine, feed and

fertilizers, and to protect and regenerate the environment).

 

Pharmaceutical substances with potent and unique health-enhancing

properties were isolated recently from medicinal mushrooms and

distributed worldwide.2 Many of them are pharmaceutical products, while

others represent a novel class of dietary supplements or

" nutraceuticals. "

 

Several antitumor polysaccharides, such as hetero-§-glucans and their

protein complexes (e.g., xyloglucans, and acidic §-glucan containing

uronic acid) as well as dietary fiber, lectins, and terpenoids, have

been isolated from medicinal mushrooms.

 

In Japan, China, Russia, and Korea, several different polysaccharide

antitumor drugs have been developed from the fruiting bodies, mycelia,

and culture media of various medicinal mushrooms, such as shiitake

(Lentinus edodes (Berk.) Sing., Tricholomataceae), reishi (Ganoderma

lucidum (Curt.:Fr.) P. Karst., Ganodermataceae), turkey tail (Trametes

versicolor (L.:Fr.) Lloyd, Polyporaceae), split gill (Schizophyllum

commune Fr.:Fr., Schizophyllaceae), mulberry yellow polypore (Phellinus

linteus (Berk. et Curt.) Teng., Hymenochaetaceae), and chaga or cinder

conk (Inonotus obliquus (Pers.:Fr.) Pilat, Hymenochaetaceae).

 

The potential of medicinal mushrooms is enormous but mostly untapped. It

could and should evolve into a successful biotechnological industry for

the benefit of humankind.

 

The study of medicinal mushrooms through the last three decades has

proved its many beneficial outcomes and has been followed by the rapid

development of manufacturing businesses dealing with commercial

cultivation of mushrooms.

 

In 1999, world production of mushrooms amounted to US$18 billion,

roughly equal to the value of coffee sales.3,4

 

Medicinal mycology has deep and firm roots in fungi's traditional uses

in the medicine of the Far East. For centuries, Chinese and other

healthcare practitioners employed mushrooms to treat various diseases.

 

They valued the power of some mushrooms as divine (e.g., a special

goddess was associated with the reishi mushroom).

 

Reishi is also considered a symbol of happy augury and good future, good

health, longevity, and even life with the immortals.

 

The use of medicinal mushrooms has gone beyond medicine itself:

different schools of Taoism employed reishi and other mushrooms as

purifiers and promoters of mind and spirit.5

 

Only at the end of the 1960s did Eastern and Western scientists start to

investigate the mechanisms of the health effects of mushrooms. The first

successful research discovered the antitumor effects of hot water

extracts from several mushroom species.6

 

The main active components proved to be polysaccharides, specifically

§-D-glucans. Chihara and his co-workers7 isolated from the fruiting

bodies of shiitake a water-soluble antitumor polysaccharide, which was

named " lentinan " after the generic name of this mushroom. This was a

major discovery.

 

Lentinan demonstrated powerful antitumor activity; preventing chemical

and viral tumor development in mice and experimental models.8,9

 

Polysaccharides displaying remarkable antitumor activity in vivo (i.e.,

through screening against sarcoma 180 in mice using intraperitoneal or

oral methods of administration) have been isolated from various species

of mushrooms belonging to the orders Auriculariales, Tremellales,

Polyporales, and Gasteromycetales.2,6,8,10-13

 

Since the discovery of lentinan, several antitumor polysaccharide agents

have been developed and commercialized, using the submerged cultured

mycelial biomass of turkey tail (Krestin, PSK; Japan), and liquid

cultured broth product of split gill (Sonifilan, SPG, Schizophyllan;

Japan).

 

These antitumor substances are regarded as biological response modifiers

that activate immunological responses. This basically means that:

 

1) they cause no harm and place no additional stress on the body;

 

2) they help the body to adapt to various environmental and biological

stresses;

 

3) they have nonspecific action on the body, supporting some or all of

the major systems, including nervous, hormonal, and immune systems, as

well as regulatory functions.

 

It is, indeed, fair to describe all major medicinal mushroom

preparations, both cellular compounds and secondary metabolites, as

having weak antigenicity and no side effects.

 

A very popular and effective preparation was developed from turkey tail

in Japan as early as 1965. A polysaccharide-peptide from this mushroom,

under the name Krestin (PSK), was developed from the strain CM-101. It

was approved for use against a number of cancers and was covered by the

Japanese healthcare plan.

 

PSK exhibits a marked effect against different types of tumors in

experimental animals when administered intraperitoneally or orally. PSK

contains 75 percent glucan and 25 percent protein.

 

In 1993, Krestin comprised 25 percent of the anticancer drug market in

Japan, and sales totaled US$350 million.10,14

 

An analogous product under the name Polysaccharide Peptide (PSP) was

developed in China from turkey tail strain Cov-1; the development

process for this strain lasted nine years, from 1983 to 1992.15 Mizuno11

stated that, in general, a period of 10 years and a total US$75 million,

or 10 billion yen, are required from the beginning of development of a

new drug to the time it is marketed.

 

Another §-D-glucan developed and popular in Japan is schizophyllan from

split gill. It is especially effective against cervical cancer.11

 

A glucan from mulberry yellow polypore was developed recently in Korea,

and an analogous polysaccharide biotechnology from this species has been

accomplished in Japan.16

 

Reishi, already mentioned as a sacred mushroom in ancient China, has

come to occupy a leading place in present-day medicinal mushroom

development. The market values of reishi-based natural healthcare

products in 1995 were estimated as US$215 million in Taiwan, US$350

million in China, US$600 million in Korea, and US$350 million in Japan.5

 

 

The physiologically active substances of reishi are water-soluble

polysaccharides and alcohol-soluble triterpenoids. Today, 119 different

triterpenoids are identified in reishi,12 about 80 of which are

biologically active.

 

Reishi dietary supplements (DS) are valued for their immunomodulating,

anticancer, antiviral properties. They are used during remission of

cancer and by hepatitis B patients. They also have anti-hyperlipidemic,

hypotensive, and hypoglycemic actions.17

 

Some 30 years ago, epidemiologists studying the native population in the

Piedade region in the suburbs of San Paulo, Brazil, noted that the rate

of occurrence of adult diseases was extremely low, and found an

association with the Agaricus species, which was a part of the regular

diet of the inhabitants of this area.18 This mushroom was identified as

A. blazei Murr., known by common names royal sun Agaricus,

himematsutake, kawarihaaratake, or almond-flavored portobello.

 

Experiments conducted in Japan with mice verified that A. blazei

significantly activates the immune system.18

 

A number of immunity-enhancing, anticancer, and antitumor fractions were

isolated from A. blazei. This species was shown to be the most effective

anticancer mushroom in a study comparing its effects with shiitake,

maitake (Grifola frondosa (Dicks.:Fr.) S.F. Gray, Polyporaceae), reishi,

and other medicinal mushrooms.

 

Fractions identified with immune effects include polysaccharides,

(1®6)-(1®3)-b-D-glucans, (1®6)-(1®4)-b-D-glucans, polysaccharide-protein

complex (ATOM), RNA-protein complexes, and glucomannan.13,18-23

 

The Japan Cancer Association proved that A. blazei is effective against

Ehrlich's ascites carcinoma,

sigmoid colon cancer, ovarian cancer, breast cancer, lung cancer, and

liver cancer, as well as against solid cancers.18

 

Higher Basidiomycetes mushrooms contain a large amount of well-balanced

essential amino acids.

 

Dietary fibers are abundant in the tissue of all mushrooms; they absorb

bile acids or hazardous materials in the intestine, and thus decrease

the chances of carcinogenic and other poisoning.

 

The overall harmonizing effect of a diet balanced with mushroom, so

highly praised by the ancient Chinese, is not a myth, but is continually

supported by modern scientific investigations.

 

Several other health-promoting effects of the mushrooms should not be

overlooked. Not only polysaccharides and triterpenoids are known as

biologically active; wide ranges of substances from higher

Basidiomycetes belonging to different classes of chemical compounds have

been described and their medicinal properties evaluated. These

substances represented glyco-

lipids (schizonellin), compounds derived from the shikimic acid

(strobilurins and oudemansins), aromatic phenols (drosophilin,

armillasirin, omphalone), fatty acid derivatives (filiboletic acid,

podoscyphic acid), polyacetylenes (agrocybin, xerulin), polyketides

(caloporoside, hericenones A-H), nucleosides (clitocine, nebularine),

different sesquiterpenes (protoilludanes, marasmanes, hirsutanes,

caryophyllanes, etc.), diterpenes (cyathin, striatal), sesterterpenes

(aleurodscal), and many other substances of different origin.2,10,24

 

Biologically active substances from higher Basidiomycetes possess

antifungal, antibacterial, and antiviral properties; they can be used as

insecticidal and nematocidal agents. In medicine they are used to

immunomodulate both humoral and cellular immune factors in the body.

 

Polyfunctional acidic glucuronoxylomannan isolated from jelly mushrooms

(Tremella spp., Tremellaceae), for instance, stimulates vascular

endothelial cells, possesses pronounced antiradiating effects,

stimulates hematogenesis, demonstrates antidiabetic, anti-inflammatory,

hypocholesterolemic, anti-allergic activities, and shows

hepatoprotective effects. It can be recommended to improve

immunodeficiency, including that induced by AIDS, physical stress or

aging, and it prevents senile degeneration of microvessels, maintaining

better blood perfusion conditions in vital organs.4

 

Most mushroom-derived preparations and substances find their use not as

pharmaceuticals, but as a novel class of dietary supplements or

" nutraceuticals. "

 

A mushroom nutraceutical is a refined or partially refined extract or

dried biomass from either the mycelium or the fruiting body of the

mushroom, which is consumed in the form of capsules or tablets as a

dietary supplement (not a conventional food) and which has potential

therapeutic applications.

 

Regular intake may enhance the immune responses of the human body,

thereby increasing resistance to disease, and in some cases, causing

regression of a disease state.

 

The market value of mushroom DS products worldwide is estimated at US$6

billion per year. The market value of reishi mushroom-based DS alone in

1995 was estimated at more than US$1.628 billion.5

 

The safety of mushroom-based dietary supplements is further enhanced

through the following controls:

 

1. The overwhelming majority of mushrooms used for production of DS are

cultivated commercially (and not gathered in the wild). This guarantees

proper identification, and pure, unadulterated products. In many cases

it also means genetic uniformity. This may also benefit conservation of

biodiversity.

 

2. Mushrooms are easily propagated vegetatively, and thus keep to one

clone. The mycelium can be stored for a long time, and the genetic and

biochemical consistency may be checked after a considerable period of

time.

 

3. Many edible and medicinal mushrooms are capable of growing in the

form of mycelial biomass in submerged cultures.4

 

This last aspect, in our experience, offers a promising future for

standardized production of safe mushroom-based DS. Submerged culture and

semi-solid state fermentation has more consistent and predictable

composition than that of fruit bodies.

 

For most substances, this mycelium biomass obtained by submerged

cultivation also has higher nutritional value. The culture media in

which mycelium grows are made of chemically pure and ecologically clean

substances. The cultivation of mushrooms for fruit body production is a

long-term process, taking one to several months for the first fruiting

bodies to appear, depending on species and substrate. By contrast, the

growth of pure mushroom cultures in submerged conditions in a liquid

culture media permits acceleration of the growth speed, resulting in

biomass yield in several days.4

 

The additional advantage of submerged culturing is the fact that most

medicinal mushrooms do not produce fruiting bodies under commercial

cultivation. Reliable industrial cultivation techniques are known for

only 37 mushroom species,3 but medicinal mushrooms include many

mycorrhizal or parasitic species that need several years for development

of normal fruiting bodies on trees.

 

Such species cannot be grown commercially, but their mycelia can be

grown easily and economically with the help of submerged culturing. High

stability and standardization of mycelium grown in submerged cultures is

important not only for producing DS, but also might be beneficial for

producing mushroom-based medicines.

 

The use of medicinal mushrooms goes hand in hand with development of

their artificial cultivation. The most significant aspect of mushroom

cultivation, if managed properly, is to create zero emissions (no

waste). Since more than 70 percent of agricultural and forest materials

are non-productive and are wasted in processing, this is a very real

advantage.25

 

Many of these waste materials can be used as substrates to grow

mushrooms. This fact gives a basis to the opinion of many researchers in

the field (including this author) that sustainable development of

mushrooms and their products in the 21st century can become a " non-green

revolution. " 3

 

Prof. Solomon P. Wasser is the Head of the International Center for

Cryptogamic Plants and Fungi, at the Institute of Evolution, University

of Haifa (Israel); and the Head of the Department of Cryptogamic Plants,

at the N.G. Kholodny Institute of Botany, National Academy of Sciences

of Ukraine.

 

Born and educated in Ukraine, Prof. Wasser earned his advanced degrees

at the N.G. Kholodny Institute of Botany, National Academy of Sciences

of Ukraine in Kiev. He was elected a member of the National Academy of

Sciences of Ukraine in 1988, and became Professor of Botany and Mycology

in 1991. He founded the International Center for Cryptogamic Plants and

Fungi at the Institute of Evolution in Haifa University in 1994 and has

directed its work since then. Since 2000, he has been a full Professor

of Haifa University (Israel).

 

In addition to his scientific studies, Prof. Wasser performs a number of

public and social activities. He is a founder and editor-in-chief of

three international journals, Algologia (Ukraine), International Journal

of Medicinal Mushrooms (USA) and International Journal on Algae (USA).

He is an author and co-author of 400 scientific publications, including

35 books and 12 patents.

 

References:

 

1. Idaho National Engineering and Environmental Laboratory. INEEL

Bioenergy Initiative. 2001 July. Available online:

<http://www.inel.gov/energy/bioenergy/web-version-bioenergy-strategic-initiative\

-dnt-v2.pdf>

 

 

2. Wasser SP, Weis AL. Medicinal properties of substances occuring in

higher Basidiomycetes mushrooms: Current perspectives [Review].

International Journal of Medicinal Mushrooms 1999;1:31-62.

 

3. Chang ST. Global impact of edible and medicinal mushrooms on human

welfare in the 21st century: nongreen revolution. International Journal

of Medicinal Mushrooms 1999;1:1-8.

 

4. Wasser SP, Nevo E, Sokolov D, Reshetnikov S, Timor-Tismenetsky M.

Dietary supplements from medicinal mushrooms: diversity of types and

variety of regulations. International Journal of Medicinal Mushrooms

2000;2:1-19.

 

5. Chang ST, Buswell JA. Ganoderma lucidum (Curt.:Fr.) P.Karst.

(Aphyllophoromycetideae) - a mushrooming medicinal mushroom.

International Journal of Medicinal Mushrooms 1999;1:139-48.

 

6. Ikekawa T, Uehara N, Maeda Y, Nakanishi M, Fukuoka F. Antitumor

activity of aqueous extracts of edible mushrooms. Cancer Res

1969;29:734-5.

 

7. Chihara G, Maeda Y, Hamuro J, Sasaki T, Fukuoka F. Inhibition of

mouse sarcoma 180 by polysaccharides from Lentinus edodes (Berk.) Sing.

Nature 1969;222:687-8.

 

8. Zakany J, Chihara G, Fachet J. Effect of Lentinan on tumor growth in

murine allogeneic and syngeneic host. Int J Cancer 1980a;25:371-6.

 

9. Zakany J, Chihara G, Fachet J. Effect of Lentinan on the production

of migration inhibitory factor induced by syngeneic tumor in mice. Int J

Cancer 1980b;26:783-8.

 

10. Mizuno T. The extraction and development of antitumor-active

polysaccharides from medicinal mushrooms in Japan [Review].

International Journal of Medicinal Mushrooms 1999;1:9-30.

 

11. Mizuno T. A development of antitumor polysaccharides from mushroom

fungi. Food & Food Ingred J (Japan). 1996;167:69-85.

 

12. Kim HW, Kim BK. Biomedicinal triterpenoids of Ganoderma lucidum

(Curt.:Fr.) P.Karst. (Aphyllophoromycetideae). International Journal of

Medicinal Mushrooms 1999;1:121-38.

 

13. Stamets P. Growing Gourmet and Medicinal Mushrooms.

Berkeley/Toronto: Ten Speed Press; 2000.

 

14. Chang ST. Mushroom biology: the impact on mushroom production and

mushroom products. In: Chang ST, Buswell JA, Chiu SW, et al, editors.

Mushroom Biology and Mushroom Products. Hong Kong: Chinese University

Press; 1993. p. 3-20.

 

15. Hiroshi S, Takeda M. Diverse biological activity of PSK (Krestin), a

protein-bound polysaccharide from Coriolus versicolor (Fr.) Quel. In:

Chang ST, Buswell JA, Chiu SW, et al, editors. Mushroom Biology and

Mushroom Products. Hong Kong: Chinese University Press; 1993. p.

237-245.

 

16. Mizuno T. The development of an antitumor BRM from song gen, or

meshimakobu, Phellinus linteus (Berk. et Curt.) Teng mushroom [Review].

International Journal of Medicinal Mushrooms 2000;2:21-34.

 

17. Wasser SP, Weis AL. Medicinal mushrooms. In: Nevo E, editor. Reishi

Mushroom (Ganoderma lucidum (Curt.:Fr.) P.Karst.) Haifa, Israel:

Peledfus; 1997. p. 1-37.

 

18. Mizuno T. 2002. Medicinal properties and clinical effects of

Agaricus blazei Murr. International Journal of Medicinal Mushrooms

2002;4 (forthcoming).

 

19. Mizuno T, Hagiwara T, Nakamura T, Ito H, Shimura K, Sumiya T,

Asakura A. Antitumor activity and some properties of water-soluble

polysaccharides from " Himematsutake, " the fruiting body of Agaricus

blazei Murrill. Agricult Biol Chem 1990;54:2889-96.

 

20. Ito H, Shimura K, Itoh H, Kawade M. Antitumor effects of a new

polysaccharide-protein complex (ATOM) prepared from Agaricus blazei

(Iwade strain 101) " Himematsutake " and its mechanisms in tumor-bearing

mice. Anticancer Res 1997;17:277-84.

 

21. Fujimiya Y, Suzuki Y, Oshiman K, Kobori K, Morigushi K, Nakashima H,

Matumoto Y, Takahara S, Ebina T, Katakura R. Selective tumoricidal

effect of soluble proteoglucan extracted from the basidiomycete,

Agaricus blazei Murrill, mediated via natural killer cell activation and

apoptosis. Cancer Immunol Immunother 1998;46:147-59.

 

22. Fujimiya Y, Yamamoto H, Niji M, Suzuki I. Peroral effect on tumor

progression of soluble beta (1,6)-glucans prepared by acid treatment

from Agaricus blazei Murr. (Agaricaceae, Higher Basidiomycetes).

International Journal of Medicinal Mushrooms 2000;2:43-50.

 

23. Cho SM, Lee Jh, Han SB, Kim BK. Chemical features and purification

of immunostimulating polysaccharides from the fruit bodies of Agaricus

blazei. Korean J Mycol 1999;27:170-4.

 

24. Lorenzen K, Anke T. Basidiomycetes as a source for new bioactive

natural products. Curr Org Chem 1998;2:329-64.

 

25. Poppe J. Use of agricultural waste materials in the cultivation of

mushrooms. In: Van Griensven DLJL, editor. Science and cultivation of

edible fungi. Rotterdam/Brookfield: A. Balkema; 2000. p. 3-24.

 

 

* Biomass includes the full range of plants and plant-derived materials,

such as dedicated energy crops and trees, agricultural food and feed

crops, agricultural crop wastes and residues, wood wastes and residues,

and municipal wastes. The majority of non-food biomass is composed

primarily of the natural polymers cellulose, hemicellulose, and lignin

and is referred to as lignocellulosic biomass. Lignocellulose is a

complex of lignin and cellulose present in the cell walls of woody

plants. Lignin is a complex organic polymer deposited in the cell walls

of plants, making them rigid and woody. Lignocellulosic material

resource, like solar energy, is sustainable. Lignocellulosic material is

a kind of biomass that is estimated to amount to 1.9x1011 tons of dry

matter on land annually.1

 

 

 

 

 

 

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