Medicinal mushrooms

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Lepista nuda

Medicinal mushrooms are mushrooms used or studied as possible treatments for disease. Research indicates mushrooms have potential antiviral, antimicrobial, anticancer, antihyperglycemic, hypocholesterolemic, and anti-inflammatory activities. The pleuromutilin antibiotics are derivatives of the mushroom isolate pleuromutilin. The mushroom isolates lentinan, PSK, and PSP, are licensed pharmaceuticals in certain countries. Fungi that do not produce mushrooms, are currently being used to manufacture paclitaxel, artemisinin, and were the original source of the first beta-lactam antibiotics, statins, immunosuppressants like ciclosporin, and antifungals like griseofulvin.

Contents

History[edit]

Mushroom artwork by Chen Hongshou, Hiroshige II, and Lang Shining (left) Mesoamerican mushroom stones (right)

Mushrooms, fermentation molds, mycelia, and lichens, have a history of medicinal use spanning millennia. The mushroom with the longest record of medicinal use Ganoderma lucidum, is known in Chinese as líng zhī ("spirit plant"), and in Japanese as mannentake ("10,000 year mushroom"). In ancient Japan, Grifola frondosa was worth its weight in silver.[1] Inonotus obliquus was used in Russia as early as the 16th century, and its medicinal properties were described by Nobel laureate Alexandr Solzhenitsyn.[2] Ancient Egyptians considered mushrooms food for royalty. Ötzi the Iceman was found carrying Fomes fomentarius and Piptoporus betulinus.[3] A Hadith states, "Truffles are manna which Allah sent to the people of Israel through Moses, and its juice is a medicine for the eyes."[4]

Research[edit]

Defensive activities[edit]

Mushrooms have antimicrobial, antiviral, and nematicidal, activities in vitro. Antibiotics retapamulin, tiamulin, and valnemulin, are derivatives of the mushroom isolate pleuromutilin. Plectasin is a mushroom derived defensin antibiotic.

The immunosuppressants ciclosporin, mycophenolic acid, mizoribine, the antibiotics penicillin, cephalosporins, fusafungine, usnic acid, fusidic acid, fumagillin, brefeldin A, verrucarin A, alamethicin, and the antifungals griseofulvin, echinocandins, strobilurin, azoxystrobin, caspofungin, micafungin, were discovered in fungi that do not produce mushrooms. Codinaeopsin is an antimalarial fungal isolate, and Sanofi uses fungi to manufacture artemisinin.[1]

Cholesterol biosynthesis inhibitors[edit]

Pleurotus creates the statin lovastatin.[5] A study noted an unidentified statin in Agaricus bisporus.[6] Zaragozic acids were discovered in fungi, and the pravastatin precursor mevastatin, was discovered in Penicillium. The red yeast rice fungus Monascus purpureus creates lovastatin, mevastatin, and the simvastatin precursor, monacolin J. Mushroom isolate eritadenine and its 3-deaza derivatives have hypocholesterolemic activity in vivo.

Anticancer activities[edit]

Lentinan, PSK, and PSP, are registered anticancer immunologic adjuvants/BRMs.[7] Irofulven and acylfulvene are anticancer derivatives of illudin S. Clavariadelphus truncatus creates the FTI clavaric acid. Inonotus obliquus creates the betulinic acid precursor betulin.[8] Flammulina velutipes creates asparaginase. Agaricus creates conjugated linoleic acid.

BMS manufactures paclitaxel using Penicillium and plant cell fermentation (PCF). Endophytic fungi can synthesize podophyllotoxin and camptothecin, precursors to etoposide, teniposide, topotecan, and irinotecan.

Vitamin D and ergothioneine[edit]

Mushrooms exposed to UV-light create significant amounts of vitamin D1, vitamin D2, and vitamin D4.[9][10] This is notable, as non-animal sources of vitamin D are practically nonexistent.

Although ergothioneine is only synthesized by mushrooms, other forms of fungi, and certain bacteria, human gene SLC22A4 ensures accumulation.

Antihyperglycemic activities[edit]

Mushrooms have antihyperglycemic activity in vivo. Inonotus obliquus creates DPP-4 inhibitors. Grifola frondosa creates α-glucosidase inhibitors.[11] Trametes versicolor creates α-amylase inhibitors, and the antihyperglycemic cyclic heptapeptide ternatin.

Psychotropic activities[edit]

Polyozellus multiplex (left) Hericium erinaceus (center)

Over 200 species of mushrooms synthesize psilocybin, and its degradation product psilocin. Due to a chemical resemblance to serotonin, psilocin is a non-selective, partial serotonin agonist.

Claviceps isolates and/or derivatives, were used to develop the headache medications cafergot, dihydroergotamine, methysergide, methylergometrine, the dementia medications hydergine, nicergoline, the Parkinson's disease medications lisuride, bromocriptine, cabergoline, pergolide, and the controlled substance lysergic acid diethylamide.

The mycorrhizal mushroom Polyozellus multiplex synthesizes prolyl endopeptidase inhibitors polyozellin, thelephoric acid, and kynapcins -12, -13, -24, -28.[12][13][14][15] The mycorrhizal mushroom Boletus badius synthesizes theanine.[16] Hericium erinaceus isolates promote nerve growth factor synthesis in vitro.

Other activities[edit]

ACE inhibitor peptides were isolated from Pleurotus, Agaricus, Ganoderma, and Flammulina. Cordycepin, inotilone, quercinol, antcin A, and benzocamphorin F, are mushroom anti-inflammatory compounds. Pholiota squarrosa contains xanthine oxidase inhibitors. Coprinopsis atramentaria contains coprine, which metabolizes to the acetaldehyde dehydrogenase inhibitor 1-aminocyclopropanol. Mushroom extracts inhibit 5-alpha reductase and/or aromatase in vitro. Other researched fungal isolates include, integrasone, ergosterol peroxide, enniatins, oudenone, velleral, peptaibols, kojic acid, beauvericin, pullulan, lichenin, gliotoxin, and asperlicin.

Edible species[edit]

Agaricus bisporus (Portobello, cremini, white button, champignon)

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

Agaricus bisporus extracts have immunomodulatory activities in vivo,[17][18] and activity against several cancer cell lines.[19]

Agaricus subrufescens (Agaricus blazei/brasiliensis, almond mushroom)

Agaricus subrufescens is a medicinal mushroom associated with Brazil and Japan.[20][21] Research and small clinical studies demonstrated Agaricus subrufescens extracts have antihyperglycemic and anticancer activities.[22][23][24][25]

Agrocybe aegerita (Pioppino, chestnut mushroom)

An Agrocybe aegerita extract demonstrated anticancer and immunomodulatory activities in vivo.[26]

Auricularia auricula (Wood ear, kikurage)

'
Auricularia auricula (left) Auricularia polytricha (right)

Auricularia auricula extracts have antihyperglycemic in vivo, and anticancer, anticoagulant, and anticholesterol activities in vitro.[27][28]

Auricularia polytricha (Cloud ear)

An Auricularia polytricha isolate inhibited sarcoma in vivo.[29]

Boletus edulis (Porcini, cep, borovik, steinpilz)

Boletus edulis (left) Coprinus comatus (center) Cordyceps attached to a caterpillar (right)

A lectin isolated from the mycorrhizal mushroom, Boletus edulis, has anticancer activity.[30]

Coprinus comatus (Ink cap)

A Coprinus comatus extract inhibited adenocarcinoma in vitro.[31]

Cordyceps sinensis (Caterpillar fungus, yartsa gunbu, dong chong xia cao)

Cordyceps sinensis is an entomopathogenic mushroom collected on the Tibetan Plateau. The immunosuppressant ciclosporin was originally isolated from Cordyceps subsessilis. The adenosine analog cordycepin was originally isolated from Cordyceps. Other Cordyceps isolates include, cordymin, cordycepsidone, and cordyheptapeptide.[32] CS-4 is a commercial strain of Cordyceps sinensis.

Flammulina velutipes (Enokitake)

Flammulina velutipes (left) cultivated Flammulina velutipes (right)

Epidemiological studies have associated Flammulina velutipes consumption with lower cancer rates.[33] FIP‐fve, proflamin, and flammulin, are Flammulina velutipes glycoproteins with anticancer and immunomodulatory activities.

Grifola frondosa (Maitake)

'
Grifola frondosa (left) Hypsizygus tessellatus (center) Lentinula edodes (right)

Grifola frondosa studies indicate potential anticancer and antihyperglycemic activities. D-fraction, MD-fraction, SX-fraction, and grifolan, are researched isolates of Grifola frondosa.

Hypsizygus tessellatus (Hypsizygus marmoreus, shimeji)

Studies have isolated antiatherosclerotic, antifungal, and immunomodulatory compounds, from Hypsizygus tessellatus.

Lentinula edodes (Shiitake)

Lentinan is an isolate of Lentinula edodes mycelia. Japan approved lentinan as an adjuvant for gastric cancer in 1985.[34] AHCC is an extract derived from fermented Lentinula edodes mycelia. The Lentinula edodes isolate eritadenine, is an inhibitor of S-adenosyl-L-homocysteine hydrolase, and has hypocholesterolemic activity. A novel serine protease inhibitor was isolated from Lentinula edodes.

Lignosus rhinocerus (Tiger milk mushroom)

Lignosus rhinocerus is a medicinal mushroom associated with Malaysia.[35]

Morchella esculenta (Morel)

'
Morchella esculenta (left) Phallus indusiatus (right)

A Morchella esculenta isolate has immunomodulatory activity in vitro.[36]

Phallus impudicus

Phallus impudicus extracts have been clinically researched in relation to venous thrombosis.[37]

Phallus indusiatus (Dictyophora indusiata, bamboo mushroom)

Medicinal use of Phallus indusiatus was first noted during the Tang Dynasty. Phallus indusiatus extracts promote NGF-synthesis and have anti-inflammatory activity in vitro. Phallus indusiatus isolates include 5-(hydroxymethyl)-2-furfural, the antibiotic albaflavenone, dictyophorines, and dictyoquinazols.

Pholiota nameko (Nameko)

Pholiota nameko (left) Pleurotus citrinopileatus (center) Pleurotus djamor (right)

Pholiota nameko creates compounds with antiinflammatory, immunomodulatory, and hypolipidemic activities.[38][39][40]

Pleurotus citrinopileatus (Golden oyster mushroom)

Pleurotus citrinopileatus extracts have antihyperglycemic activity in vivo.

Pleurotus djamor (Pink oyster mushroom)

A Pleurotus djamor isolate has anticancer activity in vitro.[41]

Pleurotus eryngii (King oyster mushroom, eringi)

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

Pleurotus eryngii extracts have immunomodulatory activities in vitro.[42] Pleurone, erylysin A and B, eryngase, ubiquinone-9, eryngeolysin, a 14 kDa phytase, eryngin, eryngiolide A, and pleureryn, are researched Pleurotus eryngii isolates.

Pleurotus ostreatus (Oyster mushroom, hiratake)

Pleurotus ostreatus creates lovastatin, chrysin, pleuran, and ACE inhibitor peptides.[43][44] Pleurotus ostreatus extracts may inhibit cholesterol biosynthesis, as well as having potential anticancer and immunomodulatory activities.[45][46][47]

Sparassis crispa (Cauliflower mushroom)

Sparassis crispa has anticancer and immunomodulating activity in vivo.[48][49][50][51][52]

Tremella fuciformis (White jelly fungus)

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Tremella fuciformis (left) Tremella mesenterica (right)

A Tremella fuciformis isolate protected against effects of radiation in vivo.

Tremella mesenterica (Golden jelly fungus)

Tremella mesenterica has potential anticancer and immunomodulating activities.[53][54][55]

Tricholoma matsutake (Matsutake, pine mushroom)

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Tricholoma matsutake (left) Ustilago maydis (center) Volvariella volvacea (right)

Isolates from the mycorrhizal mushroom, Tricholoma matsutake, have anticancer and immunomodulating activities. [56][57][58][59][60][61][62]

Ustilago maydis (Mexican truffle, huitlacoche, corn fungus)

Ustilago maydis creates ustilagine and ustilagic acid.[63]

Volvariella volvacea (Straw mushroom)

Volvariella volvacea, a mushroom associated with Southeast Asia, has anticancer activity in vitro.[64][65]

Extractable species[edit]

Astraeus hygrometricus (Earthstar)

Astraeus hygrometricus (left) Fomes fomentarius (center) Ganoderma lucidum (right)

Astraeus hygrometricus, a mushroom associated with India and China, has anticancer activity in vivo.[66][67]

Cyathus stercoreus

Cyathus stercoreus creates polyketide antioxidants, cyathusals, cyathuscavins, and pulvinatal.[68][69]

Cyathus striatus

Cyathus striatus creates cyathins, striatins, and antimicrobial compounds.[70][71][72]

Fomes fomentarius (Amadou, tinder conk)

Fomes fomentarius extracts have immunomodulatory activity in vivo, and anticancer activity in vitro.[73][74]

Ganoderma lucidum (Ling zhi, mannentake, reishi)

Ganoderma lucidum is the mushroom with the longest record of medicinal use. Ganoderma lucidum is thought to be useful against a variety of ailments. Ganoderma lucidum contains p-hydroxybenzoic acid, cinnamic acid, and lanostane-type triterpenoids like ganoderic acids.[75]

Hydnellum peckii

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Hydnellum peckii (left) Inonotus obliquus (center) Peziza vesiculosa (right)

Atromentin is an anticoagulant isolated from the mycorrhizal mushroom Hydnellum peckii.[76][77]

Inonotus obliquus (Chaga)

Inonotus obliquus has been used for centuries in Russia and Eastern Europe. Inotodiol, inotilone, melanin, trametenolic acid, and the betulinic acid precursor betulin, are researched Inonotus obliquus isolates.[8] An in vivo study showed an Inonotus obliquus extract increased the melanoma survival rate 4-fold. Additional research indicates potential anticancer activity.[78][79][80][81][82][83][84] Befungin is a commercial Russian extract of Inonotus obliquus.[85]

Peziza vesiculosa

Peziza vesiculosa creates vesiculogen, and has been researched for anticancer activity.[86][87][88][89][90]

Phellinus linteus (Meshimakobu, sanghwang)

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Phellinus igniarius (left) Piptoporus betulinus (right)

Phellinus linteus is a mushroom associated with Korea. Phellinus linteus isolates include hispidin, hispolon, phellinins, phellinstatin, interfungins A, and hypholomine B.[91] Researchers have also studied the related species P. igniarius and P. rimosus.

Piptoporus betulinus (Birch polypore)

A hydroquinone isolated from Piptoporus betulinus inhibited a matrix metalloproteinase.[92]

Polyporus umbellatus (Zhu ling)

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Polyporus umbellatus (left) Schizophyllum commune (right)

Polyporus umbellatus extracts have anti-inflammatory, anticancer, and immunomodulating activities, in vitro.[93][94][95][96][97][98][99][100]

Poria cocos (Fu ling)

Poria cocos is a medicinal fungus associated with China.[101]

Schizophyllum commune (Split gill)

Schizophyllan (SPG, sizofiran, sonifilan), an isolate of Schizophyllum commune, has been researched clinically for anticancer activity.[102] Hydrophobins were originally isolated from Schizophyllum commune. A chemically analogous polysaccharide, scleroglucan, is an isolate of Sclerotium rolfsii.

Taiwanofungus camphoratus (Antrodia camphorata/cinnamomea, niuchangchih)

Antroquinonol, antrocamphins, zhankuic acids, and antcins, are researched Taiwanofungus camphoratus isolates.

Trametes gibbosa (Daedalea gibbosa)

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Trametes gibbosa (left) Trametes versicolor (center) Xylaria hypoxylon (right)

A Trametes gibbosa extract inhibited leukemia in vivo.[103]

Trametes versicolor (Coriolus versicolor, yun zhi, kawaratake)

Medicinal use of Trametes versicolor was first noted during the Ming Dynasty. PSK (Krestin, polysaccharide-K) and PSP (polysaccharopeptide) are protein-bound polysaccharides isolated from different Trametes versicolor mycelia strains. In Japan, PSK is a gastric cancer adjuvant. Japan began using PSK in 1977, while China began using PSP in 1987.

Xylaria hypoxylon

Xylaria hypoxylon extracts have hemagglutinating, antiproliferative, and antimitogenic activities.[104][105][106][107]

Contamination hazards[edit]

Mushrooms can accumulate, even hyper-accumulate, particular heavy metals and radionuclides.[108]

See also[edit]

References[edit]

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External links[edit]

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