Medicinal Mushrooms IN THE 21ST CENTURY

Medicinal Mushrooms

IN THE 21ST CENTURY

Rhea Mehta, PhD

Contents Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 What Are Mushrooms? . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 Medicinal Mushrooms . . . . . . . . . . . . . . . . . . . . . . . . . . . 4 Reishi . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5 Lion’s Mane . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6 Shitake . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6 Turkey Tail . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7 Chaga . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7 Cordyceps . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8 Maitake . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8 Nutritional Value . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9 Major Bioactive Compounds . . . . . . . . . . . . . . . . . . . . . . 10 Polysaccharides . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11 Terpenoids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12 Phenolics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13 Therapeutic Properties . . . . . . . . . . . . . . . . . . . . . . . . . . 13 Anticancer and Immune Function . . . . . . . . . . . . . . . . . 13 Antiviral and Antibacterial . . . . . . . . . . . . . . . . . . . . . . 14 Anti-diabetic and Anti-obesity . . . . . . . . . . . . . . . . . . . 15 Antioxidant, Anti-inflammatory, and Anti-aging . . . . . . . . 15 Cardioprotective . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16 Hepatoprotective . . . . . . . . . . . . . . . . . . . . . . . . . . . 16 Neuroprotective . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17 Cultivation and Production . . . . . . . . . . . . . . . . . . . . . . . 17 Global Uses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18 Environmental Sustainability and Regeneration . . . . . . . . . . . . . . . . . . . . . . . . . . . 18 Current State of Research . . . . . . . . . . . . . . . . . . . . . . . . 20 Dietary Supplements and Pharmaceutical Drugs . . . . . . . 20 Considerations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21 Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22 Author Bio . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24

Qi Traditions seeks to honour the wisdom of the ancient healers and restore faith in the medicinal value of fungi.

INTRODUCTION THE USE OF MUSHROOMS in traditional ancient therapies dates back to at least the Neolithic Age (in China, 10,000 B.C. – 2,000 B.C). For millennia, mushrooms have been regarded and revered by humans as edible and medicinal agents. Ancient Asian traditions have stressed the importance of several mushroom species, most notably the lingzhi or reishi, lion’s mane, cordyceps, and shitake mushroom. The history of mushroom consumption is rich in Tibetan shamanism and Buddhism, as well as in spiritual cultures of Mesoamerica, Mexico, and Guatemala with the use of hallucinogenic mushroom species. Use of medicinal mushrooms has a long history in Russia, Europe, and some parts of Africa, including Nigeria, Algeria, and Egypt.

Medicinal Mushrooms in the 21st Century 1

Given the use of mushrooms in traditional therapies spanning the globe, modern researchers are attempting to validate and document some of the ancient knowledge. In the past three decades, the interdisciplinary field of science that studies mushrooms, known as mycology, has demonstrated the nutritional (culinary) and therapeutic (medicinal) value of many compounds extracted from a range of mushrooms species .

Traditionally, mushrooms were used to maintain good health, as well as to prevent and treat diseases, mainly by regulating the immune system. In the last decade scientists have identified and explored other ways in which various mushroom species promote good health, revealing mushrooms to beunique, multi-modal medicinal "Today, more than agents worthy of further investigation.

100

therapeutic applications

Today, more than 100 therapeutic applications have been demonstrated have been demonstrated by mushrooms, including by mushrooms..." antioxidant, anti-inflammatory, anticancer, antitumor, anti-diabetic, immunomodulating, antiviral, antibacterial, anticholesterolemic, antiparasitic, and antifungal. Mushrooms also protect against brain, heart, and liver damage. While modern researchers are just beginning to explore the clinical potential of medicinal mushrooms in the West, countries in the East such as Japan, Korea, China, and Russia have already adopted mushroom-derived preparations for use in clinical practice.

For example, mushrooms have been used in traditional Chinese medicine for years to treat pulmonary diseases, and in Japan, the mushroom T. versicolor has been used as an approved product for adjunctive cancer treatment since the 1970s.

The number of mushroom species on Earth is currently estimated at 150,000, yet perhaps only 10 percent are known to science. This presents researchers with an exciting opportunity to dive into this vast and largely untapped field of mushroom science with hopes of uncovering new and potentially breaththrough nutritional and therapeutic agents.

Medicinal Mushrooms in the 21st Century 2

WHAT ARE MUSHROOMS? Mushrooms comprise an extremely abundant and diverse world of fungi.

They are something special in the living world, being neither plant nor animal. Belonging to a kingdom of their own, called Myceteae, all mushrooms are heterotrophic, meaning they cannot make their own food. Instead, they absorb nutrients from other sources of organic carbon such as complex organic polymers like cellulose, which get degraded by extracellular enzymes secreted by mushrooms. Taxonomically, mushrooms can be classified into two different categories: Basidiomycetes, which comprise many of the well-known genera, and Ascomycetes.

The structures that we refer to as mushrooms are in fact only the fruiting bodies of fungi. The vegetative parts of fungi, called mycelia, are a system of cordlike strands that branch out of soil, compost, wooden logs, and other lignocellulosic materials that are host to fungi. After some time, the matured mycelia growing on such materials produce the fruiting bodies we know as mushrooms.

As mentioned, mushrooms have been used by humans for thousands of years as food and medicine. More than 14,000 mushroom species are recognized by science, and among them, about 2,000 are classified as edible. These edible mushrooms can be categorized into 30 genera, with 270 species that bear potential therapeutic value in human health.

Medicinal Mushrooms in the 21st Century 3

MEDICINAL MUSHROOMS Medicinal mushrooms possess nutraceutical and pharmaceutical characteristics in addition to taste and aroma. They are a rich source of nutrients such as carbohydrates, fibers, proteins, unsaturated fats, vitamins, and minerals. They also produce secondary metabolites, which are largely responsible for their therapeutic effects. These metabolites are bioactive, low-molecular-weight compounds that are produced in response to stress as a defense and signaling mechanism for survival. Interestingly, they are not required by the fungi for normal growth and reproduction. o NH2

N

N

A Nitrogen analog

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o H N

NH

N HO

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NH2

Theanine

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Psilocybin

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Clitocine

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B Phenol derivative

HO

H

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Grifolin

Hispolon

H

Ergosterol

HO

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O OH

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C Derivative of α β Unsaturated carbonyl

C

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Antroquinolol

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Lentinan

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Ganoderic acid

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β-glucan

Medicinal Mushroom: Boon for Therapeutic Applications, Biotech (2018) 8:334

Structure of bioactive compounds from medicinal mushroom

More than 100 species of medicinal mushrooms are used in Asia. Some of the more commonly used species are introduced below. It is worth noting that while these mushrooms have been used historically as traditional medicines, with many being used clinically today in Asia, modern research is insufficient to draw conclusions, as it has mostly been conducted in cellular and animal Medicinal Mushrooms in the 21st Century 4

studies. While many of these medicinal mushrooms have been recognized scientifically for their health-promoting activities, pharmaceutical application in healthcare is still far away in the majority of countries across the world, and especially in the West.

Today, medicinal mushrooms can be found as dietary and nutritional supplements. They are often recommended by nutritionists and holistic healthcare professionals and sold by health food and wellness retailers.

Given the lack of consensus and limited information on safety, it is a good idea to consult with your healthcare professional about appropriate dosages and risk factors with certain medications. Finally, when choosing medicinal mushrooms as dietary supplements, it is important to ensure they have been tested by a third-party facility for quality and purity and that there is sufficient information available about the product.

Reishi Ganoderma lucidum (G. lucidum), also known as reishi in Japanese Medicine or lingzhi in Chinese Medicine, is a large, dark mushroom from Asian Traditional Medicine that has been praised for its powerful health benefits for over 2,000 years. It was in the 16th-century Ming Dynasty when G. lucidum was discovered to have therapeutic value. Benefits included enhanced vital energy, improved memory, and improved cardiac function, and tonifying and anti-aging effects.

According to the State Pharmacopoeia of the People’s Republic of China, G. lucidum acts to replenish Qi, calm the mind, and reduce coughing and asthma. It is also recommended for insomnia, dizziness, shortness of breath, and heart palpitations. Since the early 1970s, cultivation of G. lucidum has become a major source of the mushroom, with popularity extending outside of Asian Traditional Medicine and into the West.

Medicinal Mushrooms in the 21st Century 5

Lion’s Mane Hericium erinaceus (H. erinaceus) is an edible mushroom with distinguished medicinal value, a long history of use in Traditional Chinese Medicine, and an established process of cultivation in Asia since the late 1980s.

H. erinaceus is referenced by several names, including yamabushitake in Japanese Medicine, houtou in Chinese Medicine, or more broadly as lion’s mane mushroom.

Lion’s mane is considered a saprotroph, or weak parasite, and grows on dead wood and occasionally on the cracks of living hardwood across Asia, Europe, and North America. More recently, it has earned scientific attention as a potential source for a variety of therapies for cancer, depression, diabetes, and diseases of the heart and nervous system.

Shitake The shiitake mushroom (Lentinula edodes) is the second most commonly consumed mushroom worldwide and has grown to become an extensively used culinary ingredient. Historically, therapeutic use of the L. edodes became widespread in the Ming Dynasty after methods of cultivating the fungus on logs were developed.

Shiitake was traditionally used as a tonic to improve circulation and vigor.

Health-promoting properties included improved heart health and efficacy against lung disease and intestinal worms. It was also associated with the treatment of chronic rheumatism and cancer. Today lentinan, one of the active ingredients purified from shiitake mushrooms, has been used experimentally and clinically as an immunopotentiation agent in the treatment of advanced gastric cancer in Japan.

Medicinal Mushrooms in the 21st Century 6

Turkey Tail Trametes versicolor (T. versicolor) or Coriolus versicolor (C. versicolor), also known as yun zhi in Traditional Chinese Medicine and kawaratake in Japanese Medicine, is a woody bracket polypore mushroom that grows on dead logs throughout the world in many diverse climates, including North America.

The name turkey tail refers to its concentric rings of brown and tan, which resemble turkey tail feathers.

Turkey tail mushroom has a long history of treasured use in Asia as food and in Asian Traditional Medicine as a therapeutic agent.

In 1965, the immunomodulatory activity of turkey tail was identified in Japan by a chemical engineer who observed a case of cancer remission after ingesting it. Subsequent research and findings led to its clinical use as a supplementary therapeutic agent in cancer treatments in Japan and China.

Chaga Chaga mushroom (Inonotus obliquus), grows as a rock-hard protrusion from birch trees in cooler climates, such as Northern Europe, Siberia, Russia, Korea, Northern Canada, and Alaska. Chaga is also referenced by other names, such as cinder conk, birch canker polymore, clinker polypore, and black mass.

Unlike the other commonly known medicinal mushrooms, this dense structure is known as a sclerotium rather than a fruiting body.

For centuries, chaga powder was used as traditional medicine in tea form in Russia and other Northern European countries to boost the immune system and improve overall health. It has also been used in the treatment of some cancers, diabetes, and heart disease.

Medicinal Mushrooms in the 21st Century 7

Cordyceps Cordyceps is a genus of parasitic fungi that grows on the larvae of insects. These mushrooms remain dormant in the soil until they attack their host, replacing its tissue and sprouting long stems that grow outside the infected host’s body. With over 750 identified species, cordyceps have been used for centuries in Traditional Chinese Medicine as a tonic, food, and medicine. However, it was in the early 1990s that cordyceps gained worldwide attention, when Chinese longdistance runners who took tonic from the species C. sinensis broke world records during their training periods.

In recent times, several cordyceps species have been shown to have medicinal value, with the most studied being C. militaris and C. sinensis.

They have the potential to help treat respiratory, liver, kidney, and heart and lung diseases, as well as type 2 diabetes and some cancers.

Maitake Grifola frondosa (G. frondosa), is an edible medicinal mushroom with a large fruiting body characterized by overlapping caps that grows at the base of stumps tree trunks of dead, dying, or aging hardwoods such as oaks, elms, and chestnuts. It is also known as hen of the woods in North America or maitake in Japan.

Maitake is mainly found in northern temperate regions of Japan, as well as in some European countries and the Northeastern United States.

G. frondosa is treasured in both Traditional Japanese and Chinese Medicine as a medicinal mushroom to boost energy and improve spleen and stomach ailments, as well as to calm the mind. Cultivation began in Japan in the early 1980s, with China and the United States beginning large-scale production a decade later.

Medicinal Mushrooms in the 21st Century 8

NUTRITIONAL VALUE The nutritional value of mushrooms typically comes from high protein, low fat, high fiber, and diverse vitamin and mineral content. Notably, mushrooms are abundant in essential amino acids leucine, valine, glutamine, and glutamic and aspartic acids. Fatty acids found in mushrooms are predominantly linoleic, oleic, and palmitic fatty acids. Carbohydrates include chitin, glycogen, trehalose, and mannitol, as well as fiber enriched sources, β-glucans, hemicelluloses, and pectic substances.

Minerals found in high quantities in mushrooms include potassium, phosphorus, magnesium, calcium, copper, iron, selenium, and zinc.

Abundant vitamins include riboflavin (vitamin B2), niacin, folates, and traces of vitamins C, B1, B12, D, and E. Mushrooms are the only non-animal food source of vitamin D and therefore the only food-based vitamin D source for vegetarians.

Medicinal Mushrooms in the 21st Century 9

MAJOR BIOACTIVE COMPOUNDS Medicinal mushrooms are a rich source of bioactive compounds, which are found in mushroom fruiting bodies, spores, cultured mycelia, and cultured broth. These compounds, also referred to as secondary metabolites, are largely responsible for the therapeutic properties of the mushrooms. They include polysaccharides, glycosides, alkaloids, volatile oils, terpenoids, tocopherols, phenolics, flavonoids, carotenoids, and lactones.

The most important secondary metabolites are polysaccharides, which belong to the 1,3-β-glucans family. Polysaccharide β-glucans or polysaccharideprotein complexes in mushroom extracts have immense therapeutic potential in human health, as they demonstrate many health-promoting benefits, including anti-diabetic, anticancer, anti-obesity, immunomodulatory, anticholesterolemic, hepatoprotective, neuroprotective, antibiotic, detoxifying, and anti-aging properties.

The immunomodulating and antitumor activity of polysaccharides or polysaccharideprotein complexes is worth highlighting because research in this area is quite extensive. Clinical trials of several mushroom polysaccharide compounds as treatment for various cancers and other diseases have been conducted in Asia. To date, over 120 medicinal functions have been identified, with the majority of research still in exploratory phase in cellular models.

"...medicinal mushrooms may be useful to both human health through drug development and environmental health through biotechnological processes."

New proteins with biological activities have also been found in medicinal mushrooms which may be useful to both human health through drug development and environmental health through biotechnological processes.

These include lignocellulose- degrading enzymes, lectins, proteases and protease inhibitors, ribosome-inactivating proteins, and hydrophobins.

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Polysaccharides Polysaccharides are the most well-researched secondary metabolites of medicinal mushrooms, with data having been collected from hundreds of different species of the higher basidiomycetes genus. As mentioned, they are best known for their antitumor and immunomodulating capacity.

Specifically, in a tumor-bearing mouse model, mushroom polysaccharides were shown to activate the immune response of the host organism, resulting in a 50% reduction in tumor size and an increase in survival. The underlying mechanism of action of polysaccharides therefore points to immunomodulation, versus a direct "This health-promoting killing of tumor cells.

activity can be

Given β-glucans are not synthesized by humans, beneficial for patients they are not recognized by the human immune with compromised system. Therefore, upon consumption, they induce both innate and adaptive immune responses as a immune systems..." protective strategy. In doing so, they protect the body from pathogenic microbes, viruses and harmful environmental toxins and carcinogens that have entered the body. This health-promoting activity can be beneficial for patients with compromised immune systems, such as those recovering from chemotherapy.

Medicinal Mushrooms in the 21st Century 11

β-glucans are the main polysaccharides found in mushrooms, with about half of the mushroom cell wall mass made up of β-glucans.

This has important implications for the industrial use of these compounds, given that many are excreted into the cell growth medium, resulting in efficiencies around recovery, purification, and characterization.

Terpenoids Recent research has brought attention to the presence of another bioactive compound abundant in mushrooms: terpenoids. Terpenoids are now among the most potent of secondary metabolites found in medicinal mushrooms, best known for their anticancer, antitumor, antimicrobial, and neuroprotective benefits. Terpenoids demonstrate a spectrum of therapeutic properties with great pharmaceutical potential.

Monoterpenes (C10)

Anti-microbial

Anti-neurodegenerative Diterpenes (C20)

Triterpenes (C10)

Anti-viral

Anti-parasitic

Sesquiterpenes (C15)

Anti-oxidant

Anti-tumour Anti-inflammatory Mushrooms: an emerging resource for therapeutic terpenoids, Biotech (2019) 9:369

An outline of the therapeutic potential of mushroom-derived terpenoids

Medicinal Mushrooms in the 21st Century 12

Phenolics Phenolic compounds are another group of secondary metabolites worth highlighting, as they exhibit a wide range of therapeutic functions including anti-inflammatory, anti- allergenic, anti-atherogenic, antimicrobial, antithrombotic, cardioprotective and vasodilating benefits.

The chief mechanism of action of this group of compounds is related to their antioxidant activity.

Medicinal mushroom: boon for therapeutic applications Biotech (2018) 8:334.

THERAPEUTIC PROPERTIES Studies have shown that medicinal mushrooms have over 125 therapeutic functions. Some of the major benefits are described below.

Anticancer and Immune Function Cancer is one of the leading causes of death worldwide, with the most common treatment being chemotherapy, which has serious side effects. The search continues for effective, non-toxic treatments.

Schematic illustration of therapeutic applications of edible mushrooms

In recent years, several species of medicinal mushrooms have been studied for their anticancer properties in human cell lines, including leukemia, breast, renal, gastric, colorectal, and cervical cancers. Mushroom polysaccharides have been identified as one of the major categories of bioactive compounds to demonstrate anticancer effects in several cancer cell lines, including colorectal, renal, and oral cancer. Other bioactive compounds have also been recognized for their therapeutic potential, such as lectins (leukaemia), triterpenes (breast cancer), and clitocine (cervical cancer).

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In the medicinal mushroom Pleurotus eryngii (eringi), the anticancer effects demonstrated by polysaccharides include increased activity of natural killer cells and cytotoxic T lymphocytes in the spleen, as well as an increase in tumor necrosis factor (TNF-Îą) and interleukin-2 in a renal cancer mouse model, thereby pointing to immune system modulation as the underlying mechanism of action. In another study, G. lucidum (reishi) was reported to increase cellular autophagy and the formation "...we are only at the very of autophagosomes in a gastric cancer cell line, demonstrating a different mechanism of action beginning of uncovering involving the removal of damaged cells.

the clinical potential of

While the beneficial effects of medicinal medicinal mushrooms..." mushrooms on boosting cellular immunity and protecting against various types of cancer have been well documented, we are only at the very beginning of uncovering the clinical potential of medicinal mushrooms, with much to consider, including extraction methods of bioactive compounds, mushroom cultivation, and safety.

Antiviral and Antibacterial Human immunodeficiency virus type 1 (HIV-1) is a highly contagious virus affecting millions of people worldwide. Current treatment for HIV-1 postpones the development of acquired immunodeficiency syndrome (AIDS), which is the disease caused by HIV-1. Research in this field continues, and medicinal mushrooms are showing exciting albeit early developments in this space.

Proteins, triterpenoids, peptides, lectins, and polysaccharide-protein complexes have all been shown to possess antiviral properties against HIV-1. One reported mechanism of action by G. lucidum (reishi) includes the inhibition of the HIV-1 reverse transcriptase enzyme, which plays a critical role in the lifecycle of the virus.

The antimicrobial activity of several medicinal mushrooms has also recently been investigated. In G. lucidum, polysaccharides were shown to inhibit the growth of pathogenic bacteria and microorganisms found in food, including Bacillus cereus, Bacillus subtilis, Escherichia coli, Aspergillus niger and Rhizopus nigricans.

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Anti-diabetic and Anti-obesity Diabetes mellitus, also known as type 2 diabetes, is a chronic metabolic disease impacting millions of people worldwide. It is defined by high blood glucose levels caused by imbalances with the insulin hormone.

Polysaccharides extracted from a number of different medicinal mushroom species have been associated with "Medicinal mushrooms reducing blood glucose levels, and for some, in increasing the secretion of insulin by β-cells, which possess antioxidant lowers blood glucose levels.

and anti-inflammatory

In one study, bioactive substances in an extract of properties, which have the G. frondosa (maitake) fruiting body decreased blood glucose levels in genetically-born diabetic been associated with many mice. Some medicinal mushrooms with alleged antiof the health-promoting diabetic properties are commercially available as properties of fungi." dietary supplements, including products containing cordyceps, lion’s mane, and maitake. Maitake, along with other medicinal mushrooms, have also shown promising anti-obesity effects, likely due to the activity of β-glucans in the mushroom extracts.

Antioxidant, Anti-inflammatory, and Anti-aging Medicinal mushrooms possess antioxidant and anti-inflammatory properties, which have been associated with many of the healthpromoting properties of fungi. G. lucidum (reishi) has been reported to increase the levels of antioxidative enzymes catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) in liver and brain homogenates of mice sera.

Medicinal mushrooms have also demonstrated anti-inflammatory activity by suppressing the production of different types of inflammatory mediators, including nitric oxide, nitric oxide synthase, nuclear factor kappa beta (NF-κΒ), tumor necrosis factor (TNF)-α, and other pro-inflammatory cytokines.

Anti-aging effects have been demonstrated in G. lucidum through the activity of ergosterols, secondary metabolites obtained from the Medicinal Mushrooms in the 21st Century 15

mushroom. These compounds have been shown to extend the lifespan of the pathogen Saccharomyces cerevisiae by regulating the expression of an oxidative stress-responsive gene. Polysaccharides in G. lucidum and other medicinal mushrooms have also been shown to prevent oxidative stress and inhibit certain enzymes responsible for aging, thereby delaying it.

Cardioprotective Cardiovascular disease is marked by high levels of low-density lipoprotein (LDL) or bad cholesterol, and low levels of high-density lipoprotein (HDL), or good cholesterol. Trans fats are primarily responsible for increasing cholesterol and triglyceride levels in the body, and other risk factors include high blood pressure and high glucose levels.

Several medicinal mushrooms have been associated with reducing total cholesterol levels in the body, including G. frondosa (maitake), H. erinaceus (lion’s mane), Pleurotus eryngii (eringi), and Hypsizygus marmoreus (bunashimeji). Various mechanisms of action have been identified, such as the inhibition of platelet aggregation, the inhibition of angiotensin, the decrease in very low-density (VLDL) lipoproteins, and improvements in lipid metabolism, with peptides being the major bioactive compounds responsible for these beneficial properties.

Hepatoprotective The liver is critical in the metabolism of drugs and the detoxification of toxic compounds. Many bioactive compounds have been shown to support liver function, including phenolics, steroids, and terpenes, largely due to their role as antioxidants. In one study, G. lucidum (reishi) showed protection against vaccine-induced liver injury in mice.

The beneficial effect of the medicinal mushroom Agaricusblazei Murill was also investigated in a small study with patients suffering from hepatitis B and liver damage. After a year of being administered the mushroom extract, patients showed normalized liver function and a reduction in critical enzymes associated with liver damage.

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Neuroprotective Recent research has demonstrated the protective effects of medicinal mushrooms on neurodegenerative diseases, such as Alzheimer’s disease.

One study reported significantly reduced amyloid β deposition in the brain, along with increased anti- oxidative enzymes and improved memory-related learning abilities in a mouse model supplemented with G. lucidum. Several other Alzheimer’s related benefits have been demonstrated by various medicinal mushrooms, including an increase in nerve growth factor production, a reduced rate of synaptic degradation, and the reversal of neuronal apoptosis.

CULTIVATION AND PRODUCTION Mushroom cultivation has many steps, including selection of mushroom fruiting culture, preparation of spawn and substrate/compost, inoculation of substrate, crop care, and finally, harvesting, handling, and proper storage of the mushrooms. There are three different categories of decomposers within the basidiomycetes genus, which represent a continuum in the metabolic transition from lignocellulosic and other organic waste materials to soil in the context of large-scale mushroom production.

Primary decomposers (e.g., oyster and shiitake mushrooms) degrade cellulose and lignin from dead wood/logs, leaves, straw, cotton seed hulls, corn cobs or peanut shells, and do not depend on other organisms or their metabolites. Secondary decomposers (e.g., button mushrooms) colonize composted materials, and tertiary decomposers (e.g., agrocybe) are found in the soil.

Today, indoor cultivation using artificial logs is a more common method for large-scale production. One method involves the use of plastic bags filled with sawdust-based substrates infused with nutrients. When the bag is colonized with mycelia, holes are poked through to enable fruiting to occur.

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GLOBAL USES As our world continues to increase in population and our collective behavior continues to harm our planet, we face three main issues: the shortage of real food, an increase in health issues and chronic diseases, and environmental deterioration.

Fascinatingly, mushrooms can address all three concerns.

It is important to remember that mushrooms, like all other fungi, lack chlorophyll. As such, they can be referred to as non-green organisms since they cannot convert solar energy to organic matter like plants do. They can, however, convert massive amounts of lignocellulosic waste produced from agriculture and forestry activities into dietary food, medicine, animal feed, and crop fertilizer. Further, they can help clean and restore soil that is damaged from chemical agricultural methods.

ENVIRONMENTAL SUSTAINABILITY AND REGENERATION Mushroom cultivation is a powerful tool to restore, replenish, and remediate our planet’s over-burdened ecosphere. Because cultivation can take place on organic waste, this presents an exciting opportunity to biologically recycle the Medicinal Mushrooms in the 21st Century 18

high amounts of accumulated natural by-products of the agro-food industry, which contribute to environmental pollution through their burning and also take up precious land space that could otherwise be used to grow crops.

Natural byproducts of the agro-food industry include dead wood and leaves, which hold several nutrients that cannot be accessed unless broken down and digested. Fungi are the only organisms in the world that can decompose such organic waste products. The process is actually done by mycelia, the vegetative part of fungi, which resembles white threads that grow from the dead wood and leaves.

These mycelia release powerful extracellular enzymes and acids that can break down cellulose and lignin, the two key components of plant fiber. In the natural ecosystem, once the process of decomposition starts, organisms from other kingdoms as well as nutrients present in the organic waste can now participate in and speed up the degradation process. The organic waste—now bio-recycled to soil through the process of mushroom cultivation—can be transformed into nutritious fertilizer or feed, useful for growing crops, feeding livestock, and for remediating soil and water damaged through chemical agricultural practices. At the same time, the mushrooms harvested through this process can be used for both nutritional (protein-enriched) and medicinal purposes, as previously described.

Mushroom cultivation in the circular economy, Appl Microbiol Biotechnol. 2018; 102(18): 7795–7803.

Use of SMS in a circular economy

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CURRENT STATE OF RESEARCH Medicinal mushroom science has made good progress over the last three decades, resulting in new classes of pharmaceutical agents in Asia and various types of dietary and nutritional supplements across the world.

The community of mushroom researchers and thought leaders has grown extensively during this time as well, owing to the rich opportunities in this field of research, both from a human health and environmental perspective.

More than 600 studies on medicinal mushrooms have been published worldwide, and numerous human clinical trials have been conducted.

Many bioactive compounds have completed the clinical trial phases in Asia and are being used to treat various cancers and other diseases.

DIETARY SUPPLEMENTS AND PHARMACEUTICAL DRUGS Medicinal mushrooms have much potential as daily dietary or nutritional supplements to benefit overall health and immune function. Today, several types of mushroom supplements are available.

As pharmaceutical agents, medicinal mushrooms are most helpful for modulating immune function and maintaining good health for immunocompromised individuals and those undergoing cancer treatment.

Major bioactive compounds that have been developed as products include polysaccharides, specifically β-glucans.

The following products are available for clinical and commercial purposes: •

krestin (PSK) and polysaccharide peptide (PSP) from Trametes versicolor

•

lentinan isolated from Lentinula edodes

Medicinal Mushrooms in the 21st Century 20

•

schizopyllan (sonifilan, sizofiran, or SPG) from Schizophyllum commune

•

befungin from Inonotus obliquus

•

D-fraction from Grifola frondosa

■

GLPS polysaccharide fraction from Ganoderma lucidum

Given the many therapeutic activities of the secondary metabolites of various medicinal mushrooms, they remain a relatively unclaimed source for drug discovery.

CONSIDERATIONS Recently, the interest in developing mushroom extracts to be marketed as dietary supplements and novel prebiotics (non-digestive β-glucans) has grown. As popularity increases, questions arise about safety, standardization, regulation, efficacy, and mechanism of action.

Given that no reputable standards or protocols are currently in place for the production, extraction, and testing of medicinal mushroom bioactive products, quality and efficacy between products vary greatly.

Other critical safety questions also remain unanswered, such as are medicinal mushroom products safe for pregnant women, or can they be consumed by young children, given immune systems in young children are not yet mature?

Concerns around dosage also exist, given the discrepancy between various forms and formulations.

Many clinical trials have determined that 500–1000mg broken down and taken over the course of the day (2-3 times) is the acceptable dosage of medicinal mushroom preparations. According to Traditional Chinese Medicine, the standard daily dose of medicinal mushrooms per day in different forms (tablets, capsules, liquid extracts, etc.) must be equivalent to approximately 100–150g of fresh mushroom material.

From a research perspective, the majority of studies with medicinal mushrooms have been performed on cellular and animal models. More clinical data from human studies is therefore required to clarify whether

Medicinal Mushrooms in the 21st Century 21

the health-promoting claims reported are valid and significant. Critical factors going forward include ensuring studies are of the highest quality, following manufacturing best practices, and developing sustainable, large-scale production of medicinal mushrooms under controlled conditions.

CONCLUSIONS Medicinal mushrooms and their bioactive compounds have the potential to act as promising source materials for both the dietary supplement and pharmaceutical industries. Medicinal mushroom cultivation can also serve to promote equitable economic growth in communities within the developing world that are subject to the accumulation of large amounts of agricultural crop residues and forest industry wastes.

What’s more, mushroom cultivation has the power to restore and regenerate soil health in a zero emissions manner, thereby positively contributing to not only human health and social change, but also to healing our planet.

The multidimensional nature of the powerful fungi is highly unique and worth celebrating, even in its current state of research and level of impact.

This is just the beginning for the abundant and diverse mushroom kingdom.

I, for one, am deeply excited about the vast opportunities within this space.

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AUTHOR BIO Rhea Mehta has a PhD in Molecular Toxicology and Nutritional Biochemistry from the University of Toronto and a Bachelor’s in Biomedical Sciences from the University of Waterloo with over 15 scientific publications. She has over 10 years of experience working as an entrepreneur and advisor at the intersection of science, health technology, and wellness. Rhea is a certified Integrative Health Coach, the founder of Global Smoothie Day, and a featured member of the Mind Body Green Collective of global health and wellness experts. In her spare time, Rhea practices and teaches meditation and kriya yoga from the Himalayan Vedantic Tradition.

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