Medicinal Mushrooms – The Fantastic Fungi World

Mushrooms are a very potent source of important antioxidants that reduce oxidative stress and improve health and quality of life. Researchers say that the association between mushroom consumption and decreased cancer risk may stem from their antioxidant properties due to the specific mushroom components ergothioneine and glutathione¹. Particularly ergothioneine, a sulfur-containing amino acid found in very high concentrations in mushrooms (and obtained exclusively from the diet), exhibits exceptionally high antioxidant activity. This helps to prevent or slow down cellular damage, which plays a crucial role in aging processes, chronic diseases, and mortality¹. As mentioned, other bioactive compounds in mushrooms, such as the polysaccharides β-glucans, also show antitumor and immunomodulatory properties.

The medicinal effects of mushrooms vary according to the type of mushroom and concentration of bioactive compounds. In the case of the antioxidant ergothioneine, it is present in higher concentrations in certain mushrooms, like oyster, king oyster, and shiitake. Let’s take a look at some different types of medicinal mushrooms.

Medicinal Mushrooms

Mushrooms have been reported to have many medicinal properties, anticancer capabilities, and protective effects against tumor development. These therapeutic and anticarcinogenic effects vary with different types of mushrooms.

Coriolus versicolor – Turkey Tail or Tunzhi in China⁵

• Considered a “magic herb” in many Asian countries and particularly in China ( versicolor medicinal properties were reported thousands of years ago in China in the “Compendium of Materia Medica” and “Shen Non-Compendium Medica.”). Ancient turkey tail formulations were and are widely used to promote good health, strength, and longevity.
• In China, at least 12 C. versicolor-based drugs are currently approved for clinical use. Both in China and Japan, extracts of this mushroom were approved and have been used in the clinical setting, especially in the field of integrated cancer therapy in conjunction with chemotherapy or radiotherapy.
• Immunomodulatory properties of Turkey Tail are due to two protein-bound polysaccharides: the polysaccharide peptide (PSP) and the glycoprotein PSK (krestin). They are mainly composed of β-glucans and are among the most studied mushroom bio-compounds.
• PSP possesses immunomodulating, antitumor, anti-inflammatory, and antiviral effects; has also shown other physiological effects, such as liver-protecting, system-balancing, antiulcer, antiaging and learning, and memory-enhancing properties, as well as reducing adverse events related to chemotherapy and radiotherapy treatments.
• PSK, like PSP, is composed mainly of β-glucans, and its activities and mechanisms are similar to PSP. Krestin showed both direct and indirect cytotoxic effects on cancer cells in vitro.
• PSK can strengthen the body’s natural immune response. It may also help improve insulin resistance and hyperlipidemia by regulating the expression of inflammatory cytokines.

Ganoderma lucidum – Ling Zhi or Reishi⁵

• Known as the “mushroom of immortality,” it is one of the world’s most widely used medicinal mushrooms today. Extensively used as an adjuvant in the treatment of various types of cancer.
• Used since ancient times in traditional Chinese medicine (included in Shen Nong’s Materia Medica (206 BC-8 AD)) to promote well-being and longevity. Now listed in the American Herbal Pharmacopoeia, Chinese Pharmacopoeia, and Therapeutic Compendium.
• Reishi is recognized for its numerous pharmacological properties, such as anticancer, hypoglycemic, immunomodulatory, antihypertensive, cytotoxic, anti-diabetic, antioxidant, antihyperlipidemic, antimutagenic, anti aging, antimicrobial, and hepatoprotective properties, and many others.
• These properties are mainly due to two major groups of compounds: triterpenes/triterpenoids and polysaccharides. These two categories of molecules are primarily responsible for the anticancer properties of reishi, both by suppressing cell proliferation, metastasis, and invasion and by promoting apoptosis, combined with its immunomodulating, immunostimulating, antioxidant, and anti-inflammatory activities.
• Triterpene compounds possess marked antitumor, antimetastatic, cytotoxic, and enzyme inhibitory properties. Polysaccharides are characterized by strong antiangiogenic and immune system-strengthening properties.
• Show potential cardioprotective activity and antiaging action and may inhibit melanogenesis.
• Reishi possesses a plethora of other bioactive metabolites with numerous effects. Some of those bioactive compounds include peptides, peptidoglycans, polyphenols, ergostan sterols and ergosterol, alkaloids, fatty acids with tumor proliferation-inhibiting action, nucleotides and nucleosides with platelet aggregation effects, and laccases with antiviral properties.

Lentinula edodes – Shiitake⁵

• Contains the β-glucan lentinan, a bioactive compound approved and used in Japan for treating cancer, especially gastric cancer, due to its immunomodulatory action.
• Lentinan activates dendritic cell function by increasing levels of tumor-infiltrating cells, stimulates T and NK cell production, restores the killer/survival cell ratio, increases FcR receptor expression, and thus promotes NK cell-mediated tumor cell killing, and increases IL-2 levels, among other effects.
• Lentinan is also able to act on the activation of inflammasomes, components of the innate immune system responsible for triggering inflammatory responses.
• Lentinan has also been used as an adjuvant in oncological therapies, such as chemotherapy.
• Polyphenols present in shiitake exhibit high free radical scavenging and catalase-like and cytotoxic activities, as well as the inhibition of cell proliferation and the induction of apoptosis.

Pleurotus spp. – Species of Pleurotus may be called oyster, abalone, or tree mushrooms⁵

• Although not one of the best-known medicinal mushrooms, they have been proven to have beneficial biological effects.
• Potential antioxidative, antimicrobial, antidiabetic, anticancer, anti-inflammatory, immunomodulatory, antihypercholesterolemic, antihypertensive, antimicrobial, hepatoprotective, and anti-aging properties. Many of the metabolites and mechanisms involved in these effects have not been totally elucidated.
• Studies have evaluated the immunomodulatory and antitumor activities of different species of Pleurotus For example, treatment with the Pleurotus ostreatus (oyster mushroom) extract in mouse models resulted in a quantitative reduction of tumor cells and cell cycle arrest, increased cytotoxicity of NK cells, and macrophage stimulation to produce nitric oxide.
• Another polypeptide (PEMP) extracted from Pleurotus eryngii demonstrated significant free radical scavenging and antitumor activity in breast, cervical, and stomach cancer cells. It inhibited tumor cell proliferation, promoted macrophage proliferation, and activated macrophage-mediated immune response.

Grifola frondosa – Maitake⁵

• One of the major medicinal mushrooms with numerous medicinal properties.
• Main bioactive metabolite is the D-fraction or GFP, a β-glucan proteoglycan compound.
• Antitumor effect: activate macrophages, T cells, and NK cells, and trigger the expression of genes involved in apoptotic stimulation, the inhibition of cell growth and proliferation and cell cycle arrest, the suppression of tumor cell migration and metastasis, and the downregulation of signaling pathways, among other beneficial effects.
• May have a hypoglycemic effect, helping to balance insulin and blood sugar.
• Many other bioactive compounds, like glycoproteins, have been extracted from maitake mushrooms and studied in terms of their beneficial effects, especially in what relates to cancer tumorigenesis.

Hericium erinaceus – Lion’s Mane⁵

• Contains important and well-studied bioactive compounds – erinacines and hericenones.
• Both these compounds can easily pass through the blood-brain barrier and have demonstrated neurotropic and neuroprotective effects. Shown to induce nerve growth factor (NGF) synthesis.
• Also exhibit antioxidative, anti-inflammatory, anticancer, immunostimulant, antidiabetic, antimicrobial, hypolipidemic, and antihyperglycemic properties.
• Most used for the treatment of neurodegenerative diseases and cognitive impairment.
• One of the main erinacine compounds, erinacin A, was shown to have a protective effect against Parkinson’s disease and ischemic stroke and significant antitumor activity.
• Erinacin C, another erinacine compound, exhibits anti neuroinflammatory and neuroprotective effects.

Antrodia cinnamomea – AC Mushroom^5,8

• Antrodia cinnamomea or Antrodia camphorate, also known as AC mushroom, is a distinctive mushroom of Taiwan, little known in the West. Possesses many therapeutic properties, one of the major ones being hepatoprotective.
• More than 78 compounds have been identified in cinnamomea, especially a high amount of terpenoids.
• The bioactive compound Anctin-A showed antitumor effects on human breast cancer cells.
• Extracts and bioactive compounds of this mushroom were reported to have various biological activities, including hepatoprotective, antihypertensive, antihyperlipidemic, anti-inflammatory,

Agaricus bisporus – common names include “Button Mushroom,” “White Mushroom,” “Cremini,” and “Portobello”^5,9

• Agaricus bisporus is the most common edible mushroom in the United States (US), accounting for about 90% of the country’s mushroom cultivation. The US is the second largest producer of this mushroom after China.
• Contain beta-glucans, ergosterol, ergothioneine, vitamin D, and flavonoids.
• Also possesses essential amino acids, peptides, glycoproteins, nucleosides, triterpenoids, lectins, fatty acids, and their derivatives.
• Potential effects as an antimicrobial, anticancer, antidiabetic, antihypercholesterolemic, antihypertensive, hepatoprotective, and antioxidant agent.
• It is recommended to include bisporus in the diet to prevent prostate cancer due to the action of conjugated linoleic acid (CLA) – which inhibits proliferation in prostate cancer cell lines.

Agaricus blazei – God’s Mushroom, Mushroom of the Sun⁵

• Contains several bioactive components that activate the immune system for a multitude of defensive functions.
• Has antitumor and immunological enhancement activity.
• Also effective for the treatment of diabetes, HIV/AIDS, hypotension, and hepatitis.
• β-glucans are the main constituents that stimulate the immune system and also act as antitumoral against myeloma and hepatic cancer.
• β-glucans influence on the immune system may result in antiallergic effects.
• Some studies have shown activity against Gram-positive and Gram-negative bacteria and may promote an antimicrobial effect.

Cordyceps spp – Caterpillar fungus, Cordyceps mushroom^10,11

• Cordyceps is usually found at high altitudes on the Himalayan plateau and is a well-known medicinal mushroom in traditional Chinese and Tibetan medicine.
• Considered an important source of energy.
• Beneficial properties include anti-cancer, anti-proliferative, anti-angiogenic, anti-metastasis, apoptosis induction, anti-inflammatory, antioxidant, anti-fibrotic, anti-arteriosclerosis, anti-hypertensive, anti-thrombotic, antimalarial, antifungal, hypolipidemic, antidiabetic, hypoglycemic, anti-asthmatic, steroidogenesis, spermatogenic, anti-aging, and immunomodulatory effects.
• Bioactive ingredients include cordycepin, polysaccharides, sterols, fatty acids, and phenolic compounds.
• These bioactive compounds have the ability to strengthen the response of the immune system and also to control its exacerbated response. The therapeutic activities involved in modulating several cell signaling pathways due to the modulation of inflammation and oxidative/nitrosative stress processes.
• Cordyceps increases the production of certain interleukins and tumor necrosis factor (TNF)-α, induces phagocytosis of macrophages, mononuclear cells, nitric oxide (NO) release, and stimulates the inflammatory response via the mitogen-activated protein kinase (MAPK) route and presents synergism with interferon (INF)-γ in the production of cytokines.

Inonotus obliquus – Chaga^12,13,14,15

• Chaga mushrooms are commonly used in traditional treatments in Eastern Europe and Asia.
• Medicinal properties described include antiviral, hypoglycemic, hypolipidemic, antioxidant, antiparasitic, immunomodulatory, anti-inflammatory, neuroprotective, anticancer properties, and anti-fatigue activity. It also has low-toxic properties and no apparent side effects.
• Several compounds, such as polysaccharides, triterpenes, polyphenols, and melanin, might be responsible for most therapeutic effects. Compounds such as betulin and betulinic acid are known for their anticancer activity, and others, such as inotodiol, have also been studied for their cytotoxic effects.
• A recent study reported that Chaga mushroom extract induced autophagy by activating AMPK and inhibiting the mTOR signaling pathway in breast cancer cells¹⁴, and other studies showed antiproliferative and cytotoxic activities on different cellular models.
• Used as complementary medicine in conventional oncology treatments, even during chemotherapy or radiotherapy.

Medicinal mushrooms are commonly produced worldwide to use as food, health supplements, and medicine. Therefore, nowadays, it is easy to find ways to consume a diversity of mushrooms daily, whether by eating whole mushrooms or consuming them in powder, tincture, or pill form.

What are you waiting for? Go get your mushrooms!

 

References

1. Ba DM, Ssentongo P, Beelman RB, Muscat J, Gao X, Richie JP. Higher Mushroom Consumption Is Associated with Lower Risk of Cancer: A Systematic Review and Meta-Analysis of Observational Studies. Adv Nutr. 2021 Oct 1;12(5):1691-1704. doi: 10.1093/advances/nmab015. PMID: 33724299; PMCID: PMC8483951.
2. Valverde ME, Hernández-Pérez T, Paredes-López O. Edible mushrooms: improving human health and promoting quality life. Int J Microbiol. 2015;2015:376387. doi: 10.1155/2015/376387. Epub 2015 Jan 20. PMID: 25685150; PMCID: PMC4320875.
3. UCLA Health. 7 health benefits of mushrooms. Jan 24, 2022. https://connect.uclahealth.org/2022/01/24/7-health-benefits-of-mushrooms/, accessed Nov 2, 2022.
4. Motta F, Gershwin ME, Selmi C. Mushrooms and immunity. J Autoimmun. 2021 Feb;117:102576. doi: 10.1016/j.jaut.2020.102576. Epub 2020 Dec 1. PMID: 33276307.
5. Venturella G, Ferraro V, Cirlincione F, Gargano ML. Medicinal Mushrooms: Bioactive Compounds, Use, and Clinical Trials. Int J Mol Sci. 2021 Jan 10;22(2):634. doi: 10.3390/ijms22020634. PMID: 33435246; PMCID: PMC7826851.
6. Yadav SK, Ir R, Jeewon R, Doble M, Hyde KD, Kaliappan I, Jeyaraman R, Reddi RN, Krishnan J, Li M, Durairajan SSK. A Mechanistic Review on Medicinal Mushrooms-Derived Bioactive Compounds: Potential Mycotherapy Candidates for Alleviating Neurological Disorders. Planta Med. 2020 Nov;86(16):1161-1175. doi: 10.1055/a-1177-4834. Epub 2020 Jul 14. PMID: 32663897.
7. Patel S, Goyal A. Recent developments in mushrooms as anti-cancer therapeutics: a review. 3 Biotech. 2012 Mar;2(1):1-15. doi: 10.1007/s13205-011-0036-2. Epub 2011 Nov 25. PMID: 22582152; PMCID: PMC3339609.
8. Ganesan N, Baskaran R, Velmurugan BK, Thanh NC. Antrodia cinnamomea-An updated minireview of its bioactive components and biological activity. J Food Biochem. 2019 Aug;43(8):e12936. doi: 10.1111/jfbc.12936. Epub 2019 Jun 4. PMID: 31368557.
9. Robinson, B., Winans, K., Kendall, A. et al. A life cycle assessment of Agaricus bisporus mushroom production in the USA. Int J Life Cycle Assess 24, 456–467 (2019). https://doi.org/10.1007/s11367-018-1456-6
10. Das G, Shin HS, Leyva-Gómez G, Prado-Audelo MLD, Cortes H, Singh YD, Panda MK, Mishra AP, Nigam M, Saklani S, Chaturi PK, Martorell M, Cruz-Martins N, Sharma V, Garg N, Sharma R, Patra JK. Cordyceps spp.: A Review on Its Immune-Stimulatory and Other Biological Potentials. Front Pharmacol. 2021 Feb 8;11:602364. doi: 10.3389/fphar.2020.602364. PMID: 33628175; PMCID: PMC7898063.
11. 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 CordycepsMedicinal Fungus and Its Nutraceutical and Therapeutic Potential. Molecules. 2020 Jun 12;25(12):2735. doi: 10.3390/molecules25122735. PMID: 32545666; PMCID: PMC7356751.
12. Lu Y, Jia Y, Xue Z, Li N, Liu J, Chen H. Recent Developments in Inonotus obliquus (Chaga mushroom) Polysaccharides: Isolation, Structural Characteristics, Biological Activities and Application. Polymers (Basel). 2021 Apr 29;13(9):1441. doi: 10.3390/polym13091441. PMID: 33947037; PMCID: PMC8124789.
13. Szychowski KA, Skóra B, Pomianek T, Gmiński J. Inonotus obliquus – from folk medicine to clinical use. J Tradit Complement Med. 2020 Aug 22;11(4):293-302. doi: 10.1016/j.jtcme.2020.08.003. PMID: 34195023; PMCID: PMC8240111.
14. Lee MG, Kwon YS, Nam KS, Kim SY, Hwang IH, Kim S, Jang H. Chaga mushroom extract induces autophagy via the AMPK-mTOR signaling pathway in breast cancer cells. J Ethnopharmacol. 2021 Jun 28;274:114081. doi: 10.1016/j.jep.2021.114081. Epub 2021 Mar 30. PMID: 33798660.
15. Géry A, Dubreule C, André V, Rioult JP, Bouchart V, Heutte N, Eldin de Pécoulas P, Krivomaz T, Garon D. Chaga ( Inonotus obliquus), a Future Potential Medicinal Fungus in Oncology? A Chemical Study and a Comparison of the Cytotoxicity Against Human Lung Adenocarcinoma Cells (A549) and Human Bronchial Epithelial Cells (BEAS-2B). Integr Cancer Ther. 2018 Sep;17(3):832-843. doi: 10.1177/1534735418757912. Epub 2018 Feb 27. PMID: 29484963; PMCID: PMC6142110.