Medicinal mushrooms

Medicinal mushrooms
Lepista nuda

Medicinal mushrooms are mushrooms, or mushroom extracts, that are 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 in parts of Asia. 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] Non-mushroom forming fungi, were the original source of penicillin, griseofulvin, lovastatin, and have shown potential in bioengineering medicines like paclitaxel.

Contents

History

Artwork with Ganoderma lucidum (artists: Chen Hongshou, Láng Shìníng)

Lentinula edodes, Grifola frondosa, Ganoderma lucidum, and Cordyceps have a history of medicinal use spanning millennia in parts of Asia. In ancient Japan, Grifola frondosa was worth its weight in silver.[6] Ganoderma lucidum is known in Chinese as língzhī (spirit plant), in Japanese as mannentake (10,000 year mushroom).

Inonotus obliquus (chaga) has a history of medicinal use spanning 500 years, in parts of Russia and Northern Europe.[7] The ancient Egyptians considered mushrooms food for royalty.[8] It is written in the Hadith, "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 several pharmacopoeias from Hungary, China, and India, include Fomes fomentarius (amadou).[1] A review noted, that as early as the 16th century, Inonotus obliquus (chaga) was used as an anticancer agent in Russia and parts of Northern Europe.[7]

Mushroom stones dating to 3000 BC, have been recovered in Mesoamerica, and were associated with the Olmec, Zapotec, Maya and Aztec.[10]

Research

Anticancer activities

Polysaccharides and polysaccharide-protein complexes from medicinal 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."[11]

Inonotus obliquus (chaga) contains betulin, a precursor to betulinic acid.[12] Conjugated linoleic acid is found in Agaricus bisporus (portobello) and Agaricus subrufescens (agaricus blazei).[13][14] Two case-control studies showed a strong correlation between mushroom consumption and reduced risk of breast cancer.[15][16] A study noted Flammulina velutipes (enokitake) producers had statistically lower cancer rates.[17]

19 species of endophytic fungi can synthesize paclitaxel, one of the most important anticancer drugs known. A fungus was the original source of griseofulvin and Fusarium oxysporum was reported producing vinblastine. Griseofulvin, taxol, and vinblastine, share the same anticancer mechanism, halting cell division at mitosis, by inhibiting microtubule activity.[18]

Anticholesterol activity and statins

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Laetiporus sulphureus (left) Polyozellus multiplex (right)
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Cantharellus cibarius (left) Lactarius camphoratus (right)

The first statins discovered mevastatin, and lovastatin, were found in non-mushroom forming fungi. Later, Pleurotus ostreatus (oyster mushroom) was found to produce lovastatin.[19] Monascus purpureus used to make red yeast rice, is capable of producing mevastatin, lovastatin, and monacolins L and J. Lentinula edodes (shiitake) contains the anticholesterol compound eritadenine.[20]

The first characterized zaragozic acids, were isolated from a sterile fungal culture of S. intermedia and L. elatius.[21]

Cognitive activities

Certain species of mushrooms contain psilocybin or psilocin, most notably Psilocybe (magic mushrooms). The compounds have also been found in members of the genera Gymnopilus, Panaeolus, Pluteus, and Inocybe, among others.[22] If consumed, psilocybin is dephosphorylated to psilocin, which closely resembles the neurotransmitter serotonin. Psilocin interacts with serotonin receptors as a partial, non-selective, agonist.[23]

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Hericium erinaceus (left) Hypsizygus tessellatus (right)

The rye fungus Claviceps purpurea (ergot) can produce ergotism if eaten, but nevertheless has led to the production of certain drugs. Drugs produced from Claviceps purpurea, include lisuride, pergolide, cabergoline, bromocriptine, intended for Parkinson's disease; cafergot, dihydroergotamine, methysergide, ergotamine, intended for headaches; and hydergine, intended for dementia. Claviceps purpurea was used for the first synthesis of lysergic acid diethylamide (LSD-25).

Polyozellus multiplex (blue chanterelle) contains kynapcins and polyozellin.[24][25][26][27] Boletus badius (bay bolete) contains L-theanine.[28] A small double-blind, placebo-controlled clinical trial, published in Phytotherapy Research in 2009, showed Hericium erinaceus (lion's mane) improved cognitive function. A small placebo-controlled study published in Biomedical Research in 2010, indicated Hericium erinaceus promoted mental well-being.

Antiviral, antifungal, antibacterial, activities

Fungi create and secrete an array of 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, and verticillin A. Non-mushroom forming fungi were used to develop the antifungals caspofungin, micafungin, griseofulvin, anidulafungin.

Mushrooms with reported in vitro antiviral, antibacterial, antifungal, and antiparasitic activities are shown in the table below.

Glycemic activities

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Ganoderma applanatum (left) Agaricus campestris (right)
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Fistulina hepatica (left) Terfeziaceae (right)
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Boletus badius (left) Ustilago maydis (right)

Researchers reported Grifola frondosa contains alpha-glucosidase inhibitors.[75] Animal research and a small clinical trial noted Grifola frondosa (maitake) may lower blood sugar levels.[76][77][78][79][80][81] Animal research and small clinical studies have shown that the following mushrooms may lower elevated blood sugar levels; Tremella fuciformis (white jelly fungus),[82][83][84] Poria cocos,[85] Ganoderma lucidum (mannentake),[86][87] Auricularia auricula-judae (jelly ear),[88] Agaricus campestris (meadow mushroom),[89] Agaricus subrufescens (agaricus blazei),[90][91][92][93][93] Inonotus obliquus (chaga),[94] Hericium erinaceus (lion's mane),[95] Agrocybe aegerita (pioppino),[96] Coprinus comatus (shaggy mane),[97] cordyceps.[98][99][100][101][102]

Vitamin D and ergothioneine

Mushrooms briefly exposed to UV light, can generate significant amounts of vitamin D2 from ergosterol.[103] Dole produces an Agaricus bisporus (portobello) powdered food condiment, that contains 150% DV vitamin D2 per teaspoon.[2] Grifola frondosa (maitake), Cantharellus cibarius (chanterelle)[104] and Lentinula edodes (shiitake) contain high levels of vitamin D2 after UV light exposure.[105][106][107]

Ergothioneine, an antioxidant that is known to accumulate in certain parts of the body, is present in Flammulina velutipes (enokitake)[108] and Agaricus bisporus.[109]

Antihormone and anti-inflammatory activity

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Geastrum saccatum (left) Russula delica (right)
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Kuehneromyces mutabilis (left) Pleurotus pulmonarius (right)

A clinical study with 21 ulcerative colitis and Crohn's disease patients showed an extract of Agaricus subrufescens (agaricus blazei) had an anti-inflammatory effect.[110] Animals studies noted extracts of Fomes fomentarius (amadou), Phellinus linteus (mesima), Ganoderma lucidum (mannentake), and Inonotus obliquus (chaga) could reduce inflammation.[111][112][113][114][115] In cell culture, extracts of Geastrum saccatum (rounded earthstar),[116]Agrocybe aegerita (pioppino),[117] and Grifola frondosa (maitake),[118] inhibited the pro-inflammatory enzyme cyclooxygenase and Piptoporus betulinus (birch polypore) demonstrated anti-inflammatory activity.[119][120] Researchers noted extracts of Pholiota squarrosa (shaggy scalycap), could act as xanthine oxidase inhibitors.

In vitro, mushroom extracts have shown potential to inhibit hormone production. Greatest in vitro inhibition of aromatase, and 5-alpha reductase, was observed with Agaricus bisporus (portobello) and Ganoderma lucidum (mannentake), respectively.[13][121][122]

Edible species

Agaricus bisporus (Portobello, white button, champignon)

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Agaricus bisporus (left) Agaricus subrufescens (right)

Mouse studies reported Agaricus bisporus consumption led to immune system stimulation,[123][124] while an in vitro study reported activity against various cancer cell lines.[125] Agaricus bisporus is reported to have the greatest antiaromatase activity in vitro.

Agaricus subrufescens (A. blazei, A. brasiliensis, A. sylvaticus)

In Japan, extracts from Agaricus subrufescens are viewed as anticancer compounds. An article from 2001, estimated usage in Japan at a half a million citizens.[126][127] A review from 2008, noted there is evidence for using Agaricus subrufescens extracts for certain cancers.[93][128][129][130]

Agrocybe aegerita (Pioppino mushroom)

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Agrocybe aegerita (left) Auricularia auricula-judae (right)

Agrocybe aegerita may have anticancer and immune enhancing activities.[131]

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

Published research indicates Auricularia auricula-judae and Auricularia polytricha may have antitumour, hypoglycemic, anticoagulant and cholesterol-lowering activities.[3][4]

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.[132]

Coprinus comatus (Shaggy mane, ink cap)

An extract of Coprinus comatus inhibited the proliferation and viability of a androgen-sensitive human prostate adenocarcinoma cell line.[133]

Flammulina velutipes (Enokitake, winter mushroom)

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Flammulina velutipes (cultivated vs. wild)

Flammulina velutipes contains compounds with antitumor activity, and epidemiological studies in Japan have associated the mushroom with lower cancer rates.[17] Animal research showed the mushroom may inhibit cancer development.[134][135]

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

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Grifola frondosa (left) Lentinula edodes (right)

A review by Massachusetts General Hospital, advocated researching Grifola frondosa in relation to cancer, diabetes, and immune function.[136] Grifola frondosa contains alpha glucosidase inhibitors[137] and has been featured in clinical trials.[138] Researched extracts of Grifola frondosa include grifolan and maitake D-fraction.[139]

Lentinula edodes (Shiitake, black forest mushroom)

Lentinan and Active Hexose Correlated Compound (AHCC), are 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."[140] Research has shown AHCC may offer antiviral activity.[141][142][143]

Lentinus edodes mycelia (LEM) extract, is a researched extract derived from the mushroom.[144]

Morchella esculenta (Morel)

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Morchella (left) 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.[145]

Phallus impudicus

Although Phallus impudicus is not considered a choice edible, a review noted extracts from the mushroom have anti-tumor activity.[146] The mushroom was also studied clinically, in relation to venous thrombosis.[147]

Pleurotus djamor (Pink oyster mushroom)

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Pleurotus djamor (left) Pleurotus eryngii (right)

An extract of Pleurotus djamor was found to inhibit proliferation of hepatoma cells and breast cancer cells in vitro.[148]

Pleurotus eryngii (King oyster mushroom, eringi)

An extract of Pleurotus eryngii stimulated immune function in vitro.[149]

Pleurotus ostreatus (Oyster mushroom, hiratake)

Pleurotus ostreatus (left) Sparassis crispa (right)

Pleurotus ostreatus contains the statin lovastatin.[150][151] A number of animal studies have shown Pleurotus ostreatus consumption lowers cholesterol levels. Research with Pleurotus ostreatus demonstrated activity against various cancer cell lines[152] and animals studies have shown an anticancer effect.[153][154]

Sparassis crispa (Cauliflower mushroom)

Animal studies have shown Sparassis crispa has potential anticancer and immune enhancing activities.[155][156][157][158][159]

Tremella fuciformis (White jelly fungus, silver ear)

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Tremella fuciformis (left) Tremella mesenterica (right)

Tremella fuciformis is occasionally used in Chinese medicine as an immune tonic and for treating exhaustion.

Tremella mesenterica (Golden jelly fungus)

Tremella mesenterica has potential anticancer and immune enhancing activities.[160][161][162]

Tricholoma matsutake (Matsutake)

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Tricholoma matsutake (left) Astraeus hygrometricus(right)

Tricholoma matsutake may enhance immune function via an alpha-glucan polysaccharide.[163][164][165][166][167][168][169]

Volvariella volvacea (Paddy straw mushroom)

Volvariella volvacea is a mushroom used extensively in Thai and Vietnamese cuisines. Recent studies have indicated possible anticancer and immunomodulating activities.[170][171]

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 noted the mushroom may have hepatoprotective, antihypertensive, anti-hyperlipidemic, immuno-modulatory, anticancer, anti-inflammatory and antioxidant activities.[172]

Astraeus hygrometricus (Earthstar)

Astraeus hygrometricus is documented in Chinese and Indian herbal medicine. Research has shown the mushroom may contain immunomodulators.[173] In a mouse model, the mushroom demonstrated anticancer properties.[174]

Cordyceps

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Cordyceps militaris (left) Ganoderma lucidum (right)

The immunosuppressant drug, ciclosporin, was isolated from Tolypocladium inflatum, an anamorph of Cordyceps subsessilis. Cordycepin, was isolated from Cordyceps sinensis and Cordyceps militaris.[175] Limited clinical data supports the use of cordyceps for fatigue, bronchitis and coughs.[176] Cordyceps may improve exercise performance in healthy older subjects.[177]

Fomes fomentarius (Amadou, tinder conk)

A review noted several pharmacopoeias from Hungary, China, and India, include Fomes fomentarius.[5] Fomes fomentarius was found with Ötzi the Iceman. Research with mice showed an extract of Fomes fomentarius altered immune function and in vitro research showed an anticancer effect.[178][179]

Ganoderma lucidum (Mannentake, língzhī, reishi)

Ganoderma lucidum is described in Shennong Ben Cao Jing, Bencao Gangmu, and occasionally seen in Chinese artwork.

Research demonstrated Ganoderma lucidum may have anticancer[180][181] and immune system enhancing properties.[182][183] Animal studies have noted Ganoderma lucidum have hepatoprotective activities.[184][185] Research has shown that Ganoderma lucidum contains compounds that may act as ACE inhibitors,[186] inihibit blood platelets,[187] and have antifibrotic activity.[188] According to Memorial Sloan-Kettering, "in clinical studies, Ganoderma lucidum increased plasma antioxidant capacity and enhanced immune responses in advance-stage cancer patients."[189]

Hydnellum peckii (Red-juice tooth)

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Hydnellum peckii (left) Poria cocos (right)

Hydnellum peckii contains atromentin, an anticoagulant.[190][191]

Inonotus obliquus (Chaga)

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Inonotus obliquus (left) Peziza vesiculosa(right)

A Russian extract of Inonotus obliquus is known as befungin.[192] Russian literature nobel prize laureate, Alexandr Solzhenitsyn, wrote two pages on the speculated anticancer activities of Inonotus obliquus in Cancer Ward. Inonotus obliquus contains melanin and betulin, a precursor to the anticancer compound betulinic acid.[12]

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.[94][193][194][195][196][197][198]

Peziza vesiculosa (Orange fairy-cup)

Research has shown Peziza vesiculosa may have anticancer and immune enhancing activities.[199][200][201][202][203]

Phellinus linteus (Meshimakobu, sang-hwang)

Phellinus linteus is a medicinal mushroom associated with Korea. "Scientists have demonstrated that the extracts from fruit-bodies or mycelium of Phellinus linteus not only stimulate the hormonal and cell-mediated immune function and quench the inflammatory reactions caused by a variety of stimuli, but also suppress the tumor growth and metastasis. 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."[204]

Phellinus linteus is known to contain interfungins A, a compound that may protect against hyperglycemia-mediated protein damage.[205]

Piptoporus betulinus (Birch polypore, birch bracket)

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Piptoporus betulinus (left) Fomes fomentarius (right)

Piptoporus betulinus may have anticancer properties.[206] Ötzi the Iceman was found carrying Piptoporus betulinus wrapped in a leather string. Researchers have noted the mushroom was most likely used medicinally, after Ötzi was noted to be infected by an intestinal parasite.[207]

Polyporus umbellatus (Zhu-ling)

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Polyporus umbellatus(left) Schizophyllum commune(right)

Polyporus umbellatus may have anticancer and immune enhancing activities.[208][209][210][211][212][213][214][215]

Poria cocos (Fu-ling, hoelen)

A review published in 2009, noted, Poria cocos may have anticancer and immune enhancing activities.[216]

Schizophyllum commune (Split gill)

"Schizophyllan an isolate of Schizophyllum commune, is relatively similar to lentinan in composition and biological activity, and its mechanism of immunomoduation and anti-tumour action appears to be quite similar."[217]

Sclerotinia sclerotiorum

SSG is a a highly branched beta-1,3-glucan extract of Sclerotinia sclerotiorum. SSG has been researched for possible health benefits.

Trametes gibbosa (Daedalea gibbosa)

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Trametes gibbosa (left) Trametes versicolor (right)

An extract of Daedalea gibbosa inhibited chronic myeloid leukemia in a mouse model.[218]

Trametes versicolor (Turkey tail, yun-zhī, kawaratake)

Polysaccharide-K (Krestin, PSK) and polysaccharide peptide (PSP), are isolates of Trametes versicolor.

According to MD Anderson Cancer Center, "PSP may have positive effects upon immune parameters, percent body fat and disease progression in patients with non-small cell lung cancer based upon one randomized and blinded controlled clinical trial. PSK may have positive effects upon disease and survival outcomes based upon the preponderance of findings from randomized controlled studies; however, the lack of blinding in these trials is a cause of concern."[219]

Heavy metals

Mushrooms produced in contaminated conditions can accumulate, even hyper-accumulate, particular heavy metals.

The following is a list of observed relationships between mushrooms and heavy metal accumulations. Agaricus bisporus cadmium, mercury. Agaricus subrufescens cadmium, mercury. Agaricus campestris cadmium, lead (10x), mercury (10x). Boletus edulis cadmium (10x), cesium (including Cs-137), lead, mercury (250x), copper. Cantharellus cibarius cesium (2x). Coprinus comatus arsenic (21x), cadmium (8x), mercury (27x). Flammulina velutipes arsenic. Hydnellum peckii cesium. Morchella lead (70-100x). Pleurotus ostreatus cadmium, mercury (65-140x). Pleurotus pulmonarius cadmium, mercury, copper. Trametes versicolor mercury.[220]

See also

References

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