Medicinal mushrooms

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Lepista nuda

Medicinal mushrooms are mushrooms, or mushroom extracts, used or studied as possible treatments for diseases. Lentinula edodes (shiitake), Grifola frondosa (maitake), Ganoderma lucidum (mannentake), and Cordyceps, have a history of medicinal use spanning millennia. Research has indicated mushrooms have possible cardiovascular, anticancer, antiviral, antibacterial, antiparasitic, antiinflammatory, hepatoprotective, and glycemic, activities. Several mushroom extracts PSK,[1] PSP,[2] AHCC, lentinan,[3] and schizophyllan, are considered nutraceuticals.[4][5] Many species of endophytic fungi can synthesize paclitaxel, while Penicillium fungi were the original source of penicillin, the first statins, and griseofulvin.

Contents

[edit] History

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Artwork with Ganoderma lucidum and Umbilicaria esculenta (artists: Chen Hongshou, Hiroshige II, Láng Shìníng) (left) Pre-Columbian Mesoamerican mushroom stones (right)

Mushrooms, sclerotium, cultivated molds, lichens, and other forms of fungi, have a history of medicinal use spanning millennia. Known in Chinese as língzhī ("spirit plant"), in Japanese as mannentake ("10,000 year mushroom"), Ganoderma lucidum is the best documented medicinal mushroom. In ancient Japan, Grifola frondosa was worth its weight in silver.[6] Inonotus obliquus (chaga) was used in Russia as early as the sixteenth century, and its medicinal properties were described by Nobel laureate Alexandr Solzhenitsyn.[7] The ancient Egyptians considered mushrooms food for royalty.[8]

The Hadith states, "truffles (desert truffle) are manna which Allah, sent to the people of Israel through Moses, and its juice is a medicine for the eyes".[9] A review noted, Fomes fomentarius (amadou) is included in pharmacopoeias from Hungary, China, and India.[1] Fomes fomentarius and Piptoporus betulinus were found in the possession of Ötzi the Iceman.[10] Pre-Columbian Mesoamerican cultures used certain mushrooms for therapeutic and spiritual purposes.[11]

[edit] Research

Anticancer activities

Compounds from mushrooms may enhance innate immune responses, resulting in antitumor activities. "While the mechanism of their antitumor actions is still not completely understood, stimulation and modulation of key host immune responses by these mushroom polymers appears central. Several of the mushroom polysaccharide compounds have proceeded through phases I, II, and III clinical trials and are used extensively and successfully in Asia to treat various cancers and other diseases."[12]

More than two dozen species of endophytic fungi can synthesize paclitaxel, one of the most important anticancer drugs known.[2] Fungi were the original source of griseofulvin, and reportedly capable of synthesizing vinblastine. Griseofulvin, taxol, and vinblastine, share the same anticancer mechanism, inhibiting microtubule activity, causing a halt in cell division at mitosis.[13]

Inonotus obliquus (chaga) contains betulin, a precursor to betulinic acid.[14] Agaricus bisporus (portobello) and Agaricus subrufescens (agaricus blazei) contain CLA.[15][16] Epidemiological studies show a correlation between mushroom consumption and reduced risk of cancer.[17][18][19]

Anticholesterol activity and statins

4.statinscompounds.png

Lovastatin and mevastatin were the first statins discovered. Lovastatin was found in Aspergillus terreus and later Pleurotus ostreatus (oyster mushroom). Mevastatin, was found in Penicillium citrinum. Mevastatin is used to synthesize pravastatin, while lovastatin is used to synthesize simvastatin. Red yeast rice, made from the fungus Monascus purpureus, contains lovastatin and mevastatin.

Lentinula edodes (shiitake) contains the anticholesterol compound eritadenine.[20] Zaragozic acids, were first isolated from S. intermedia and L. elatius.[21]

Psychotropic activities

Hericium erinaceus (left) Polyozellus multiplex (center) Psilocybe cubensis (right)

Over 200 species of mushrooms, most notably Psilocybe (magic mushrooms), contain psilocybin and psilocin. Psilocybin is readily converted to psilocin, the primary psychoactive compound. Chemically, psilocin is similar to serotonin, differing only by the hydroxyl group on the 4-position of the tryptamine ring, rather than the 5th, and having two additional methyl groups on the end nitrogen.[22]

Claviceps purpurea (ergot) sclerotium can cause ergotism, yet is a source of trehalose and ergoline alkaloids. Medicines consisting of, or made from ergoline alkaloids include, lisuride, pergolide, cabergoline, bromocriptine, intended for Parkinson's disease; cafergot, dihydroergotamine, methysergide, ergotamine, intended for headaches. Nicergoline and hydergine intended for dementia. Ergotamine, and lysergic acid, isolates of Claviceps purpurea, are precursors to lysergic acid diethylamide (LSD).

Polyozellus multiplex (blue chanterelle) contains kynapcins and polyozellin.[23][24][25][26] Boletus badius (bay bolete) contains L-theanine.[27] A small double-blind, placebo-controlled clinical trial showed Hericium erinaceus (lion's mane) improved cognitive function. A small placebo-controlled study indicated Hericium erinaceus promoted mental well-being.

Antiviral, antifungal, antibacterial, activities

Lacking an immune system, fungi must create and secrete antiviral, antibacterial, antifungal, and antiparasitic compounds. Antibiotic compounds isolated from mushrooms includes, coprinol, campestrin, ganomycin, sparassol, armillaric acid, cortinellin, and ustilagic acid. Non-mushroom forming fungi were the original source of the antibiotics penicillin, cephalosporin, fusidic acid, usnic acid, and verticillin A. Non-mushroom forming fungi were used to develop the antifungals caspofungin, micafungin, griseofulvin, anidulafungin.

Glycemic activities

Ganoderma applanatum (left) Hypsizygus tessellatus (center) Geastrum saccatum (right)

Research demonstrated the following mushrooms lowered blood sugar levels in vivo; Tremella fuciformis (white jelly fungus),[74][75][76] Poria cocos,[77] Ganoderma lucidum (mannentake),[78][79] Auricularia auricula-judae (jelly ear),[80] Agaricus campestris (meadow mushroom),[81] Agaricus subrufescens (agaricus blazei),[82][83][84][85][85] Inonotus obliquus (chaga),[86] Hericium erinaceus (lion's mane),[87] Agrocybe aegerita (pioppino),[88] Coprinus comatus (shaggy mane),[89] cordyceps.[90][91][92][93][94]

Animal research and a small clinical trial noted Grifola frondosa may lower blood sugar levels.[95][96][97][98][99][100] Researchers reported Grifola frondosa (maitake) contains alpha-glucosidase inhibitors, which are known to have hypoglycemic activity.[101]

Ergocalciferol (vitamin D2) and ergothioneine

Kuehneromyces mutabilis (left) Pleurotus pulmonarius (center) Cantharellus cibarius (right)

Mushrooms briefly exposed to UV light, can generate significant amounts of vitamin D2 from ergosterol.[102] Mushrooms documented using UV light in this manner include, Agaricus bisporus (portobello),[3] Grifola frondosa (maitake), Cantharellus cibarius (chanterelle)[103] and Lentinula edodes (shiitake).[104][105][106]

Ergothioneine, an antioxidant that is known to accumulate in certain parts of the body, is present in Flammulina velutipes (enokitake)[107] and Agaricus bisporus.[108]

Antihormone and anti-inflammatory activity

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Fistulina hepatica (left) Terfeziaceae (right)

A small clinical study showed an extract of Agaricus subrufescens (agaricus blazei) had an anti-inflammatory effect.[109] Animals studies noted extracts of Fomes fomentarius (amadou), Phellinus linteus (mesima), Ganoderma lucidum (mannentake), and Inonotus obliquus (chaga) could reduce inflammation.[110][111][112][113][114] In cell culture, extracts of Geastrum saccatum (rounded earthstar),[115]Agrocybe aegerita (pioppino),[116] and Grifola frondosa (maitake),[117] inhibited cyclooxygenase and Piptoporus betulinus (birch polypore) demonstrated anti-inflammatory activity.[118][119] Researchers noted Pholiota squarrosa (shaggy scalycap) contains xanthine oxidase inhibitor compounds.

In cell culture, many mushrooms inhibit aromatase, and 5-alpha reductase activity. Greatest inhibition of aromatase and 5-alpha reductase was observed with Agaricus bisporus (portobello) and Ganoderma lucidum (mannentake) respectively.[15][120][121]

[edit] Edible species

Agaricus bisporus (Portobello, white button, champignon, crimini) Agaricus subrufescens (A. blazei, A. brasiliensis, A. sylvaticus)

Agaricus bisporus (left) Agaricus subrufescens (center) Agrocybe aegerita (right)

Agaricus bisporus is the world's most popular mushroom. Research with the mushroom demonstrated immune system stimulation in vivo,[122][123] while an in vitro study demonstrated activity against various cancer cell lines.[124]

Agaricus subrufescens has been traditionally used as a health food in Brazil. It has been reported that 100,000–300,000 kg of dehydrated Agaricus subrufescens is produced every year in Japan. Agaricus subrufescens is reportedly used by 300,000–500,000 persons for anticancer activity.[125][126] A review from 2008, noted there is evidence for using Agaricus subrufescens extracts for certain cancers.[85][127][128][129] Many extracts of the mushroom have been researched, including a hemicellulase-digested extract known as ABPC.

Agrocybe aegerita (Pioppino mushroom)

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Auricularia auricula-judae (left) Auricularia polytricha (right)

Agrocybe aegerita may have anticancer and immune enhancing activities.[130]

Auricularia auricula-judae (Jelly ear, kikurage) Auricularia polytricha (Cloud ear)

Research indicates Auricularia auricula-judae and Auricularia polytricha may have antitumour, hypoglycemic, anticoagulant and cholesterol-lowering activities.[4][5]

Boletus edulis (Porcini, cep, borovik, steinpilz, herrenpilz)

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Boletus edulis (left) Coprinus comatus (right)

A lectin from Boletus edulis was found to inhibit several malignant cell lines and bind to a neoplastic cell specific T-antigen disaccharide.[131]

Coprinus comatus (Shaggy mane, ink cap)

An extract of Coprinus comatus inhibited the proliferation of an adenocarcinoma cell line.[132]

Dictyophora indusiata (Bamboo mushroom, Phallus indusiatus)

Dictyophora indusiata contains various bioactive compounds (dictyophorine A/B, dictyoquinazol B/C, ribonucleases, tyrosinase inhibitors) and has antioxidant, inflammatory, and antimicrobial properties.

Flammulina velutipes (Enokitake, winter mushroom)

Dictyophora indusiata (left) Flammulina velutipes (middle) cultivated Flammulina velutipes (right)

Flammulina velutipes contains compounds with antitumor activity, and epidemiological studies in Japan have associated the mushroom with lower cancer rates.[19] Animal research showed the mushroom may inhibit cancer development.[133][134] FIP‐fve is a documented immunomodulatory protein isolated from Flammulina velutipes.

Grifola frondosa (Maitake, hen-of-the-woods)

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Grifola frondosa (left) Lentinula edodes (right)

A 2009 review advocated researching Grifola frondosa in relation to cancer, diabetes, and immune function.[135] Grifola frondosa contains alpha glucosidase inhibitors[136] and has been featured in clinical trials.[137] Researched extracts of Grifola frondosa include D-fraction, SX-fraction, and grifolan.[138]

Lentinula edodes (Shiitake, black forest mushroom)

Lentinan, Active Hexose Correlated Compound (AHCC), and Lentinus edodes mycelia extract (LEM), are researched isolates of Lentinula edodes. "There have been numerous clinical trials of Lentinan in Japan, though none have been placebo-controlled and double-blinded. However, Lentinan has been approved for clinical use in Japan for many years, and is manufactured by several pharmaceutical companies. Intraperitoneal lentinan is widely used as an adjuvant treatment for certain cancers in Japan and China."[139] Clinical research has shown AHCC may offer anticancer activity.[6]

Lignosus rhinocerus (Tiger milk mushroom)

Lignosus rhinocerus is a medicinal mushroom used by local communities in Malaysia. Little research has been published regarding this mushroom.[7]

Morchella esculenta (Morel)

Morchella esculenta (left) Volvariella volvacea (center) Phallus impudicus (right)

Morchella esculenta contains small amounts of hydrazine, which is destroyed upon cooking. A galactomannan from Morchella esculenta stimulated immune function in vitro.[140]

Phallus impudicus (Stinkhorn)

A review noted extracts from Phallus impudicus have anti-tumor activity.[141] The mushroom was also studied clinically, in relation to venous thrombosis.[142]

Pleurotus djamor (Pink oyster mushroom) Pleurotus eryngii (King oyster mushroom) Pleurotus ostreatus (Oyster mushroom)

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Pleurotus djamor (left) Pleurotus eryngii (right)
Pleurotus ostreatus (left) Sparassis crispa (right)

Extracts from Pleurotus djamor and [143] Pleurotus eryngii, have shown potential immunomodulatory activities.[144]

Pleurotus ostreatus contains lovastatin and pleuran.[145][146] A number of animal studies have shown Pleurotus ostreatus consumption lowers cholesterol levels. Research with Pleurotus ostreatus extracts and pleuran, demonstrated potential anticancer and immunomodulatory activities.[147][148][149]

Sparassis crispa (Cauliflower mushroom)

Animal studies have shown Sparassis crispa has anticancer and immunomodulating activities.[150][151][152][153][154]

Tremella fuciformis (White jelly fungus, white fungus) Tremella mesenterica (Golden jelly fungus)

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Tremella fuciformis (left) Tremella mesenterica (right)

Tremella fuciformis is a mushroom used in traditional Chinese medicine as a tonic for treating exhaustion. A modern drink containing the fungus is sold in Thailand as "Bird's Nest".

Tremella mesenterica has potential anticancer and immunomodulating activities.[155][156][157]

Tricholoma matsutake (Matsutake)

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Tricholoma matsutake (left) Astraeus hygrometricus(right)

Tricholoma matsutake a prized edible, may contain bioactive alpha-glucan polysaccharides.[158][159][160][161][162][163][164]

Volvariella volvacea (Paddy straw mushroom)

Recent studies have indicated Volvariella volvacea has possible anticancer and immunomodulating activities.[165][166]

[edit] Extractable species

Mushroom cell walls contain chitin, which is indigestible. To break down chitin, and allow digestion, a heated extraction process is required. The following mushrooms can be consumed only in the form of tea, herbal tonic, or medicinal soup.

Antrodia camphorata (Zhang-zhī)

Antrodia camphorata is a medicinal mushroom associated with Taiwan. Research has shown the mushroom may have hepatoprotective, antihypertensive, anti-hyperlipidemic, immuno-modulatory, anticancer, anti-inflammatory and antioxidant activities.[167]

Astraeus hygrometricus (Earthstar)

Astraeus hygrometricus is documented in Chinese and Indian herbal medicine. Research has shown the mushroom may contain immunomodulators,[168] with anticancer activity.[169]

Cordyceps Spp.

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Cordyceps militaris (left) Ganoderma lucidum (right)

Cordyceps are an entomopathogenic fungus species. Cordyceps are still collected on the Tibetan Plateau and valued for medicinal use. Cordycepin and cordymin were isolated from C. sinensis and C. militaris.[170] The immunosuppressant drug, ciclosporin, was isolated from Tolypocladium inflatum, an anamorph of C. subsessilis. Limited clinical data supports the use of Cordyceps for fatigue and bronchitis.[171]

Fomes fomentarius (Amadou, tinder conk)

Research with mice showed an extract of Fomes fomentarius altered immune function and in vitro research showed an anticancer effect.[172][173]

Ganoderma lucidum (Mannentake, língzhī, reishi)

From a historical perspective, Ganoderma lucidum is the best documented medicinal mushroom. Many Ganoderma extracts have been studied, including ganoderic acids. Research demonstrated Ganoderma lucidum may have anticancer,[174][175] immunomodulating,[176][177] hepatoprotective activities,[178][179] ACE inhibitors,[180] blood platelet inhibitors,[181] and have antifibrotic activity.[182] According to Memorial Sloan-Kettering, "in clinical studies, Ganoderma lucidum increased plasma antioxidant capacity and enhanced immune responses in advance-stage cancer patients."[183]

Hydnellum peckii (Red-juice tooth)

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Hydnellum peckii (left) Ustilago maydis (right)

Hydnellum peckii contains atromentin, an anticoagulant.[184][185]

Inonotus obliquus (Chaga)

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Inonotus obliquus (left) Peziza vesiculosa(right)

Inonotus obliquus is a medicinal mushroom associated with Russia. A Russian extract of Inonotus obliquus is known as Befungin.[186] Inonotus obliquus contains melanin and betulin, a precursor to the anticancer compound betulinic acid.[14] An experiment with mice, and an Inonotus obliquus extract, showed a 4-fold increase in survival rate of melanoma. Additional research indicates potential anticancer activity.[86][187][188][189][190][191][192]

Peziza vesiculosa (Orange fairy-cup)

Research has shown Peziza vesiculosa may have anticancer and immunomodulating activities.[193][194][195][196][197]

Phellinus linteus (Meshimakobu, sang-hwang)

Phellinus linteus is a medicinal mushroom associated with South Korea. A Harvard Medical School review noted, "Mounting evidence from different research groups has shown that Phellinus linteus induces apoptosis in a host of murine and human carcinomas without causing any measurable toxic effects to their normal counterparts."[198] A study noted interfungins A, a compound isolated from Phellinus linteus, had comparable activity to aminoguanidine.[199]

Piptoporus betulinus (Birch polypore, birch bracket)

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Piptoporus betulinus (left) Fomes fomentarius (right)

Piptoporus betulinus may have anticancer properties.[200]

Polyporus umbellatus (Zhu-ling)

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Polyporus umbellatus(left) Schizophyllum commune(right)

Polyporus umbellatus may have anticancer and immunomodulating activities.[201][202][203][204][205][206][207][208]

Poria cocos (Fu-ling, hoelen)

A review published in 2009, noted, Poria cocos may have anticancer and immunomodulating activities.[209]

Schizophyllum commune (Split gill)

Schizophyllan is an isolate of Schizophyllum commune. There is some clinical evidence for the antitumor activity of schizophyllan.[8]

Sclerotinia sclerotiorum

SSG is extracted from the non-mushroom-forming, white mold, Sclerotinia sclerotiorum. SSG has been researched for possible health benefits.

Trametes gibbosa (Daedalea gibbosa) Trametes versicolor (Coriolus versicolor, turkey tail, yun-zhī, kawaratake)

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Trametes gibbosa (left) Trametes versicolor (right)

An extract of Daedalea gibbosa inhibited leukemia in vivo.[210]

Polysaccharide-K (Krestin, PSK) and polysaccharide peptide (PSP), are isolates of Trametes versicolor. According to Memorial Sloan-Kettering, "Coriolus versicolor is a mushroom of the Basidiomycetes class. It was used initially in Traditional Chinese medicine as a tonic, but recent studies suggest that it has immunostimulant and anti-tumor properties. Polysaccharide-K (PSK), a proprietary product derived from Coriolus, was developed for cancer treatment in Japan. When used as an adjuvant, PSK appears to improve survival rates in patients with gastric and colorectal cancers."[211]

[edit] Contamination hazards

Incomplete list of observed relationships between mushrooms and heavy metals

Mushrooms produced in contaminated conditions can accumulate, even hyper-accumulate, particular heavy metals including radioactive Cs-137. Certain strains of "radiation eating fungi" have also been observed thriving in highly radioactive environments, converting gamma radiation into chemical energy for growth.

[edit] See also

[edit] References

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