Medicinal Mushrooms – emerging medicines

Mushrooms are the ‘fruiting bodies’ produced by about 14,000 different species of fungi. They are the part of the fungi we see, but in fact most of the fungi lies below the soil or tissue of the host as a massive network of thread-like cells known as the mycelium. The mushroom is simply a reproductive organ which like the flower of a plant bursts forth to spread its spores, then dies away again.

Mushrooms have been used as foods and medicines for many thousands of years by all if not virtually all traditional cultures around the world. Local knowledge and customs around the gathering and usage of wild mushrooms, based on edible or non-edible (poisonous) species and the customary usage of certain species as medicines, is ingrained into rural communities in every continent. Much of this knowledge is however now being lost, due to migration of rural populations to cities, and the demise of traditional living practices and natural ecosystems(1).

Fungi come in many different shapes, colours and forms, and given their incredible diversity, its hardly surprising that medicinal fungi exhibit a wide spectrum of pharmacological properties. Predominant ones include anti-inflammatory, antioxidant, immunomodulatory, antiviral, antibacterial, osteoprotective, nephroprotective, hepatoprotective, anti-diabetic, cognitive enhancing and anticancer actions(2).  This is an impressive repertoire, and underlines their traditional uses to help protect against and treat many different illnesses and health-related conditions.

Medicinal mushrooms have attracted much more research interest in recent years, and this has spurred a lot of product development. Some that have been particularly well researched and achieved high acclaim, are various species used widely for thousands of years in traditional Chinese and Asian medicine.

Active constituents:

These vary depending on the species, but until fairly recently most attention has been on a type of polysaccharide known as the β-glucans. We are now, however, also recognising  the importance of other compounds such as the di- and tri-terpenoids, and the fungal steroidal compound ergosterol. Mushrooms are also rich in various nutrients and other bioactive compounds including alkaloids, lectins, phenolic acids, polyunsaturated fatty acids, vitamins, and minerals. Some also contain reasonable levels of protein, with contents of 5-20% (dried weight), being fairly typical(3).

Sourcing:

Medicinal mushrooms were historically taken from the wild from the dead wood of trees or other locations, and this remains the means of gathering in traditional practices. Commercial supplies now though, derive from both wildcrafted and cultivated sources. The latter are cultivated on growth medium such as rice and other grains, and this as well as how they are dried or processed following harvest, can influence their phytochemical makeup and thus medicinal properties. Debate is ongoing for instance, about whether undigested grain can sometimes dilute down the active phytochemicals in a mycelial mass. Other quality control considerations such as the actual part(s) of the fungi used, the need to ensure product authenticity and purity, and the importance of preventing pesticide and heavy metal contamination, also apply(4).

Reishi (Ganoderma lucidum):

Known as Reishi in Japan and Ling Zhi in China, Reishi is considered a symbol of happiness and a good future, good health and longevity. There are over 2000 papers published on it in the peer-reviewed literature, and more than 400 different bioactive compounds have been characterised. Its inventory of reported pharmacological activities is vast, and includes immunomodulation, anti-atherosclerotic, anti-inflammatory, analgesic, chemo-preventive, antitumour, chemo and radio protective, sleep promoting, antibacterial, antiviral (including anti-HIV), hypolipidemic, anti-fibrotic, hepatoprotective, anti-diabetic, anti-androgenic, anti-angiogenic, antioxidative and radical-scavenging, anti-aging, hypoglycemic, oestrogenic activity and anti-ulcer properties.  Evidence from clinical trials to date suggests it can be a safe and useful adjunct to conventional cancer treatment, although further and larger trials are needed(5).

Lions Mane (Hericium erinaceous)

Lions mane has been used for centuries throughout China and Japan for general debility and a mood tonic, and for various digestive disorders(6). Nerve protective (neuroprotective) actions mediated through its antioxidant action as well as perhaps via stimulating Nerve Growth Factor (NGF) have been reported.

A trial involving 30 patients with mild dementia, reported improvements in cognitive function following 16 weeks treatment with 3g Lions Mane per day(7), and another reported  increased cognitive function in participants aged 50 and over following 12 weeks treatment(8). A small trial found evidence of anxiolytic and antidepressant effects, after 4 weeks administration to women in Japan(9).

More trials are underway, to further explore the effects of this beautiful white waterfall-like fungus, on the human psyche.

Other well-known Asian species include Cordyceps militaris (Orange caterpillar fungus), which grows inside caterpillars, consuming the tissue of its host before bursting forth to release its spores.  It is used for respiratory, kidney, liver and cardiovascular diseases, low libido, impotence, hyperlipidaemia, hyperglycaemia and as a tonic for fatigue, convalescence, and to promote energy(10, 11, 12). Several Chinese clinical trials involving people with varying levels of chronic kidney failure, have also reported an ability to improve kidney function, reduce anaemia, and act as a useful adjunct to the drug cyclosporine, which has a predisposition to cause kidney damage (13, 14, 15)

Shiitake (Lentinula edodes) is rich in antioxidants and has been shown to support healthy immune T-cell function. Maitake (Grifola frondosa) is another popular species with potential applications in neurodegenerative diseases, and whose fruiting body and fungal mycelium have antitumour and immunomodulatory activities(16).

The above has hardly touched the edges of the amount of information now available on these increasingly popular mushroom species, which are being utilised as foods, medicines and natural health products around the world. Given the clever evolutionary nature of fungi and their ability to grow on a range of decaying organic matter and symbiotically with other plant species while producing a diverse array of highly bioactive compounds, it is perhaps a reflection of the circularity of everything in nature that so many of them seem to have a powerful ability to help humans and other animals deal with chronic health conditions often seen with aging, and to live healthier lives.

Future opportunies for Aotearoa

Aotearea New Zealand has a fascinating mix of native, endemic and introduced fungi. Several of our native medicinal fungi are endangered, including Cordyceps robertsii (āwheto) and Hericium novae-zelandiae (pekepekekiore), a cousin of Lion’s Mane. Little research into their medicinal actions has taken place, although University of Auckland researchers have found extracts of Hericium novae-zelandiae to have anti-proliferative effects on three prostate cancer cell lines(17, 18).

The rich environmental and species diversity of Aotearoa New Zealand and our growing realisation of the medicinal properties of so many fungi, lends itself to the identification, mapping, analysis, bioactivity testing, agronomy work, cultivation, and commercialization of both native and introduced mushroom species. Their potential as foods and medicines, and as facilitators of a more natural biodegradation of waste, warrants much more research into medicinal fungi in Aotearoa’s future.

References:

  1. Ramírez-Terrazo A, Adriana Montoya E, Garibay-Orijel R, Caballero-Nieto J, Kong-Luz A, Méndez-Espinoza C. Breaking the paradigms of residual categories and neglectable importance of non-used resources: the “vital” traditional knowledge of non-edible mushrooms and their substantive cultural significance. J Ethnobiol Ethnomed. 2021;17(1):28. Published 2021 Apr 21.
  2. Anusiya G, Gowthama Prabu U, Yamini NV, et al. A review of the therapeutic and biological effects of edible and wild mushrooms. Bioengineered. 2021;12(2):11239-11268.
  3. Chang S, Buswell J. Medicinal Mushrooms: Past, Present and Future. Adv Biochem Eng Biotechnol. 2022 Feb 27. doi: 10.1007/10_2021_197. Epub ahead of print. PMID: 35220455.
  4. Hobbs C. Medicinal Fungi: Chemistry, Activity, and Product Assurance. HerbalGram, Journal of the Americal Botanical Council, 113, Feb-Apr 2017.
  5. Jin X, Ruiz Beguerie J, Sze DM, Chan GC. Ganoderma lucidum (Reishi mushroom) for cancer treatment. Cochrane Database Syst Rev. 2016 Apr 5;4(4):CD007731.
  6. Wang M, Gao Y, Xu D, Konishi T, Gao Q. Hericium erinaceus (Yamabushitake): a unique resource for developing functional foods and medicines. Food Funct. 2014 Dec;5(12):3055-64.
  7. Mori K, Inatomi S, Ouchi K, Azumi Y, Tuchida T. Improving effects of the mushroom Yamabushitake (Hericium erinaceus) on mild cognitive impairment: a double-blind placebo-controlled clinical trial. Phytother Res. 2009 Mar;23(3):367-72.
  8. Saitsu Y, Nishide A, Kikushima K, Shimizu K, Ohnuki K. Improvement of cognitive functions by oral intake of Hericium erinaceus. Biomed Res. 2019;40(4):125-131.
  9. Nagano M, Shimizu K, Kondo R, Hayashi C, Sato D, Kitagawa K, Ohnuki K. Reduction of depression and anxiety by 4 weeks Hericium erinaceus intake. Biomed Res. 2010 Aug;31(4):231-7.
  10. Ashraf SA, Elkhalifa AEO, Siddiqui AJ, Patel M, Awadelkareem AM, Snoussi M, Ashraf MS, Adnan M, Hadi S. Cordycepin for Health and Wellbeing: A Potent Bioactive Metabolite of an Entomopathogenic Cordyceps Medicinal Fungus and Its Nutraceutical and Therapeutic Potential. Molecules. 2020 Jun 12;25(12):2735.
  11. Cao C, Yang S, Zhou Z. The potential application of Cordyceps in metabolic-related disorders. Phytother Res. 2020 Feb;34(2):295-305. doi: 10.1002/ptr.6536. Epub 2019 Oct 31. PMID: 31667949.
  12. Phull AR, Ahmed M, Park HJ. Cordyceps militaris as a Bio Functional Food Source: Pharmacological Potential, Anti-Inflammatory Actions and Related Molecular Mechanisms. Microorganisms. 2022 Feb 10;10(2):405.
  13. Li Y, Xue WJ, Tian PX, Ding XM, Yan H, Pan XM, Feng XS. Clinical application of Cordyceps sinensis on immunosuppressive therapy in renal transplantation. Transplant Proc. 2009 Jun;41(5):1565-9.
  14. Luo Y, Yang SK, Zhou X, Wang M, Tang D, Liu FY, Sun L, Xiao L. Use of Ophiocordyceps sinensis (syn. Cordyceps sinensis) combined with angiotensin-converting enzyme inhibitors (ACEI)/angiotensin receptor blockers (ARB) versus ACEI/ARB alone in the treatment of diabetic kidney disease: a meta-analysis. Ren Fail. 2015 May;37(4):614-34.
  15. Sun T, Dong W, Jiang G, Yang J, Liu J, Zhao L, Ma P. Cordyceps militaris Improves Chronic Kidney Disease by Affecting TLR4/NF-κB Redox Signaling Pathway. Oxid Med Cell Longev. 2019 Mar 31;2019:7850863.
  16. Wu JY, Siu KC, Geng P. Bioactive Ingredients and Medicinal Values of Grifola frondosa (Maitake). Foods. 2021 Jan 5;10(1):95
  17. Chen ZG , Bishop KS , Tanambell H , Buchanan P , Smith C , Quek SY . Characterization of the bioactivities of an ethanol extract and some of its constituents from the New Zealand native mushroom Hericium novae-zealandiae. Food Funct. 2019 Oct 16;10(10):6633-6643.
  18. Chen ZG, Bishop KS, Tanambell H, Buchanan P, Quek SY. Assessment of In Vitro Bioactivities of Polysaccharides Isolated from HericiumNovae-Zealandiae. Antioxidants (Basel). 2019 Jul 8;8(7):211.

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