Medicinal uses of fungi explained

Medicinal fungi are fungi that contain metabolites or can be induced to produce metabolites through biotechnology to develop prescription drugs. Compounds successfully developed into drugs or under research include antibiotics, anti-cancer drugs, cholesterol and ergosterol synthesis inhibitors, psychotropic drugs, immunosuppressants and fungicides.

History

Although fungi products have long been used in traditional medicine, the ability to identify beneficial properties and then extract the active ingredient started with the discovery of penicillin by Alexander Fleming in 1928.[1] Since that time, many potential antibiotics were discovered and the potential for various fungi to synthesize biologically active molecules useful in various clinical therapies has been under research. Pharmacological research identified antifungal, antiviral, and antiprotozoan compounds from fungi.[2]

Ganoderma lucidum, known in Chinese as líng zhī ("spirit plant"), and in Japanese as mannentake ("10,000-year mushroom"), has been well studied. Another species of genus Ganoderma, G. applanatum, remains under basic research. Inonotus obliquus was used in Russia as early as the 16th century; it featured in Alexandr Solzhenitsyn's 1967 novel Cancer Ward.[3]

Research and drug development

Cancer

There is no good evidence that any type of mushroom or mushroom extract can prevent or cure cancer.[4]

11,11'-Dideoxyverticillin A, an isolate of marine Penicillium, was used to create dozens of semi-synthetic, candidate anticancer compounds.[5] 11,11'-Dideoxyverticillin A, andrastin A, barceloneic acid A, and barceloneic acid B, are farnesyl transferase inhibitors that can be made by Penicillium.[6] 3-O-Methylfunicone, anicequol, duclauxin, and rubratoxin B, are anticancer/cytotoxic metabolites of Penicillium.

Penicillium is a potential source of the leukemia medicine asparaginase.[7]

Some countries have approved beta-glucan fungal extracts lentinan, polysaccharide-K, and polysaccharide peptide as immunologic adjuvants.[8]

Antibacterial agents (antibiotics)

Alexander Fleming led the way to the beta-lactam antibiotics with the Penicillium mold and penicillin. Subsequent discoveries included alamethicin, aphidicolin, brefeldin A, cephalosporin,[9] cerulenin, citromycin, eupenifeldin, fumagillin,[9] fusafungine, fusidic acid,[9] helvolic acid,[9] itaconic acid, MT81, nigrosporin B, usnic acid, verrucarin A, vermiculine and many others.

Antibiotics retapamulin, tiamulin, and valnemulin are derivatives of the fungal metabolite pleuromutilin. Plectasin, austrocortilutein, austrocortirubin, coprinol, oudemansin A, strobilurin, illudin, pterulone, and sparassol are under research for their potential antibiotic activity.

Cholesterol biosynthesis inhibitors

Statins are an important class of cholesterol-lowering drugs; the first generation of statins were derived from fungi.[10] Lovastatin, the first commercial statin, was extracted from a fermentation broth of Aspergillus terreus.[10] Industrial production is now capable of producing 70 mg lovastatin per kilogram of substrate.[11] The red yeast rice fungus, Monascus purpureus, can synthesize lovastatin, mevastatin, and the simvastatin precursor monacolin J. Nicotinamide riboside, a cholesterol biosynthesis inhibitor, is made by Saccharomyces cerevisiae.

Antifungals

Some antifungals are derived or extracted from other fungal species. Griseofulvin is derived from a number of Penicillium species;[12] caspofungin is derived from Glarea lozoyensis.[13] Strobilurin, azoxystrobin, micafungin, and echinocandins, are all extracted from fungi. Anidulafungin is a derivative of an Aspergillus metabolite.

Antivirals

Many mushrooms contain potential antiviral compounds remaining under preliminary research, such as: Lentinus edodes, Ganoderma lucidum, Ganoderma colossus, Hypsizygus marmoreus, Cordyceps militaris, Grifola frondosa, Scleroderma citrinum, Flammulina velutipes, and Trametes versicolor, Fomitopsis officinalis.[14] [15] [16] [17]

Immunosuppressants

Cyclosporin was discovered in Tolypocladium inflatum, while Bredinin was found in Eupenicillium brefeldianum and mycophenolic acid in Penicillium stoloniferum. Thermophilic fungi were the source of the fingolimod precursor myriocin. Aspergillus synthesizes immunosuppressants gliotoxin and endocrocin. Subglutinols are immunosuppressants isolated from Fusarium subglutinans.[18]

Malaria

Codinaeopsin, efrapeptins, zervamicins, and antiamoebin are made by fungi, and remain under basic research.[19]

Diabetes

Many fungal isolates act as DPP-4 inhibitors, alpha-glucosidase inhibitors, and alpha amylase inhibitors in laboratory studies. Ternatin is a fungal isolate that may affect hyperglycemia.[20]

Psychotropic effects

Numerous fungi have well-documented psychotropic effects, some of them severe and associated with acute and life-threatening side-effects.[21] Among these is Amanita muscaria, the fly agaric. More widely used informally are a range of fungi collectively known as "magic mushrooms", which contain psilocybin and psilocin.[21]

The history of bread-making records deadly ergotism caused by ergot, most commonly Claviceps purpurea, a parasite of cereal crops.[22] Psychoactive ergot alkaloid drugs have subsequently been extracted from or synthesised starting from ergot; these include ergotamine, dihydroergotamine, ergometrine, ergocristine, ergocryptine, ergocornine, methysergide, bromocriptine, cabergoline, and pergolide.[23] [24]

Vitamin D2

Fungi are a source of ergosterol which can be converted to vitamin D2 upon exposure to ultraviolet light.[25] [26] [27]

Yeasts

The yeast Saccharomyces is used industrially to produce the amino acid lysine, as well as recombinant proteins insulin and hepatitis B surface antigen. Transgenic yeasts are used to produce artemisinin, as well as insulin analogs.[28] Candida is used industrially to produce vitamins ascorbic acid and riboflavin. Pichia is used to produce the amino acid tryptophan and the vitamin pyridoxine. Rhodotorula is used to produce the amino acid phenylalanine. Moniliella is used industrially to produce the sugar alcohol erythritol.

External links

Notes and References

  1. Web site: Discovery and Development of Penicillin . American Chemical Society, International Historic Chemical Landmarks . 11 March 2020 . 2020.
  2. Engler M, Anke T, Sterner O . Production of antibiotics by Collybia nivalis, Omphalotus olearis, a Favolaschia and a Pterula species on natural substrates . Zeitschrift für Naturforschung C . 53 . 5–6 . 318–24 . 1998 . 9705612 . 10.1515/znc-1998-5-604 . 7189999 . free .
  3. Zheng W, Miao K, Liu Y, Zhao Y, Zhang M, Pan S, Dai Y . Chemical diversity of biologically active metabolites in the sclerotia of Inonotus obliquus and submerged culture strategies for up-regulating their production . Applied Microbiology and Biotechnology . 87 . 4 . 1237–54 . July 2010 . 20532760 . 10.1007/s00253-010-2682-4 . 22145043 . free .
  4. Web site: Medicinal mushrooms in cancer treatment . Cancer Research UK . 4 November 2022 .
  5. News: Trafton . Anne . Research update: Chemists find help from nature in fighting cancer . MIT News . 27 February 2013 .
  6. Overy . David P. . Larsen . Thomas O. . Dalsgaard . Petur W. . Frydenvang . Karla . Phipps . Richard . Munro . Murray H.G. . Christophersen . Carsten . Andrastin A and barceloneic acid metabolites, protein farnesyl transferase inhibitors from Penicillium albocoremium: chemotaxonomic significance and pathological implications . Mycological Research . November 2005 . 109 . 11 . 1243–1249 . 10.1017/s0953756205003734 . 16279417 .
  7. Shrivastava A, Khan AA, Shrivastav A, Jain SK, Singhal PK . Kinetic studies of L-asparaginase from Penicillium digitatum . Preparative Biochemistry & Biotechnology . 42 . 6 . 574–81 . 2012 . 23030468 . 10.1080/10826068.2012.672943 . 30396788 .
  8. Ina K, Kataoka T, Ando T . The use of lentinan for treating gastric cancer . Anti-Cancer Agents in Medicinal Chemistry . 13 . 5 . 681–8 . June 2013 . 23092289 . 3664515 . 10.2174/1871520611313050002 .
  9. Broadbent . Douglas . Antibiotics Produced by Fungi . The Botanical Review . July 1966 . 32 . 3 . 219–242 . 10.1007/BF02858660 . 4353729 . 1966BotRv..32..219B . 23442996 .
  10. Tobert JA . Lovastatin and beyond: the history of the HMG-CoA reductase inhibitors . Nature Reviews. Drug Discovery . 2 . 7 . 517–26 . July 2003 . 12815379 . 10.1038/nrd1112 . 3344720 .
  11. Jahromi MF, Liang JB, Ho YW, Mohamad R, Goh YM, Shokryazdan P . Lovastatin production by Aspergillus terreus using agro-biomass as substrate in solid state fermentation . Journal of Biomedicine & Biotechnology . 2012 . 196264 . 2012 . 23118499 . 3478940 . 10.1155/2012/196264 . free .
  12. Book: Block, Seymour Stanton . [{{Google books|3f-kPJ17_TYC|page=631|plainurl=yes}} Disinfection, Sterilization, and Preservation ]. 2001 . Lippincott Williams & Wilkins . 978-0-683-30740-5 . 631 .
  13. Book: Richardson. Malcolm D. . Warnock . David W. . Malcolm Richardson . Fungal Infection Diagnosis and Management . 978-1-4051-1578-0 . 2003. Wiley .
  14. Book: 10.1007/978-981-13-6382-5_10 . Antiviral Potency of Mushroom Constituents . Medicinal Mushrooms . 2019 . Pradeep . Prabin . Manju . Vidya . Ahsan . Mohammad Feraz . 275–297 . 978-981-13-6381-8 . 181538245 .
  15. Friedman M . Mushroom Polysaccharides: Chemistry and Antiobesity, Antidiabetes, Anticancer, and Antibiotic Properties in Cells, Rodents, and Humans . Foods . 5 . 4 . 80 . November 2016 . 28231175 . 5302426 . 10.3390/foods5040080 . free .
  16. Zhang T, Ye J, Xue C, Wang Y, Liao W, Mao L, Yuan M, Lian S . 6 . Structural characteristics and bioactive properties of a novel polysaccharide from Flammulina velutipes . Carbohydrate Polymers . 197 . 147–156 . October 2018 . 30007599 . 10.1016/j.carbpol.2018.05.069 . 51629395 .
  17. Girometta C . Fomitopsis officinalis in the light of its bioactive metabolites: a review . Mycology . 10 . 1 . 32–39 . March 2019 . 30834150 . 6394315 . 10.1080/21501203.2018.1536680 .
  18. Kim H, Baker JB, Park Y, Park HB, DeArmond PD, Kim SH, Fitzgerald MC, Lee DS, Hong J . 6 . Total synthesis, assignment of the absolute stereochemistry, and structure-activity relationship studies of subglutinols A and B . Chemistry: An Asian Journal . 5 . 8 . 1902–10 . August 2010 . 20564278 . 10.1002/asia.201000147 .
  19. Nagaraj G, Uma MV, Shivayogi MS, Balaram H . Antimalarial activities of peptide antibiotics isolated from fungi . Antimicrobial Agents and Chemotherapy . 45 . 1 . 145–9 . January 2001 . 11120957 . 90252 . 10.1128/aac.45.1.145-149.2001 .
  20. Lo HC, Wasser SP . Medicinal mushrooms for glycemic control in diabetes mellitus: history, current status, future perspectives, and unsolved problems (review) . International Journal of Medicinal Mushrooms . 13 . 5 . 401–26 . 2011 . 22324407 . 10.1615/intjmedmushr.v13.i5.10 .
  21. Web site: Hallucinogenic mushrooms drug profile . The European Monitoring Centre for Drugs and Drug Addiction .
  22. Web site: Shiel . William C. . Medical Definition of Ergotism . MedicineNet . 18 October 2020.
  23. Schiff . Paul L. . Ergot and Its Alkaloids . American Journal of Pharmaceutical Education . September 2006 . 70 . 5 . 98 . 10.5688/aj700598 . 17149427 . 1637017 .
  24. Schade R, Andersohn F, Suissa S, Haverkamp W, Garbe E . Dopamine agonists and the risk of cardiac-valve regurgitation . The New England Journal of Medicine . 356 . 1 . 29–38 . January 2007 . 17202453 . 10.1056/NEJMoa062222 . free .
  25. Keegan RJ, Lu Z, Bogusz JM, Williams JE, Holick MF . Photobiology of vitamin D in mushrooms and its bioavailability in humans . Dermato-Endocrinology . 5 . 1 . 165–76 . January 2013 . 24494050 . 3897585 . 10.4161/derm.23321 .
  26. Kamweru PK, Tindibale EL . Vitamin D and Vitamin D from Ultraviolet-Irradiated Mushrooms (Review) . International Journal of Medicinal Mushrooms . 18 . 3 . 205–14 . 2016 . 27481154 . 10.1615/IntJMedMushrooms.v18.i3.30 .
  27. Cardwell . Glenn . Bornman . Janet . James . Anthony . Black . Lucinda . A Review of Mushrooms as a Potential Source of Dietary Vitamin D . Nutrients . 13 October 2018 . 10 . 10 . 1498 . 10.3390/nu10101498 . 30322118 . 6213178 . free .
  28. News: Peplow . Mark . Sanofi launches malaria drug production . Chemistry World . 16 April 2013 .

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