Wild and cultivated mushrooms as food, pharmaceutical and industrial products

Introduction. Mushrooms have been consumed since earliest times and have been recognized for their attractive sensory and culinary attributes; besides, they contain high amounts of bioactive and health-promoting compounds. This review is devoted to wild edible mushrooms and their role in the life of modern man. Materials and methods. Literature research using scientific publications on the topics related to wild mushrooms as a food resource, their applications in medicine and pharmaceuticals, as well as the methods for mushroom cultivation was conducted. Results and discussion. Wild edible mushrooms have high nutritional value, contain high-quality proteins, fiber, essential fatty acids, vitamins, including D2, microelements, as well as valuable compounds such as polyphenols, terpenoids, sterols, while having a low energy value, which makes it possible to use them in cooking and in low-calorie diets. Wild edible mushrooms have various specific pharmaceutical properties that can be used in the treatment of various serious diseases. The gathering and use of wild edible mushrooms for food make a significant contribution to both the solution of the global food shortage crisis and economics of different countries around the world, and could be considered in some countries as new sources of income for local people. The increase of interest on mushroom consumption along human history at worldwide level has led to the development of basic and sophisticated techniques for their cultivation. Solid-state and submerged liquid fermentations are nowadays useful methods for cultivation of mushroom in a large-scale for production of volumes of biomass and of valuable specific bioactive metabolites. An interesting and unusual method to grow edible mushrooms of Ustilago maydis , which are considered a delicacy produced by the natural infection of the maize ears, is described. Conclusions. The role that the mushroom kingdom plays in human life is extremely important and varied. In the near future, their role in local economies around the world and as raw materials


Introduction
Mushrooms are considered to be among the most mysterious forms of life on our planet (Lincoff, 1981).Mushroom belonging to the phylum Basidiomycota is the fleshy fruiting body of a certain type of fungus, typically formed over the substrate used for fungi growth.Wild mushrooms have been recognized as a source of food and medicine from ancient times.Thus, it was proved that about 18,700 calendar years ago people ate mushrooms: spores of Agaricales and Boletales were found in a tooth plaque of a woman buried in the Upper Palaeolithic in northern Spain (Straus et al., 2015).
Legends and superstitions that existed among various peoples associated with mushrooms have come down (Bertelsen, 2013).The Egyptians considered mushrooms to be plants of immortality being a gift from the god Osiris and called them "the flesh of the gods" (Budge, 2017).According to the laws of ancient Egypt, only the pharaoh and his entourage could consume mushrooms, but common people were not allowed to even touch them.In Greek mythology, the growth of mushrooms came from lightning sent to earth by Zeus, as they appeared after thunderstorms.To the ancient Romans mushrooms were "the foods of the Gods" (Niksic et al., 2016), and mushrooms were included in the menu for special occasions (Rahi and Malik, 2016).
The images of mushrooms have been found in prehistoric cave paintings, the oldest of which, found in caves in the Sahara Desert (Tassili, Algeria) and in southern India, which were made by Prehistoric Early Gatherers in 9000-7000 B.P. (Before the Present) and in 1000 B.C. (Before Christ) -100 A.C. (After Christ), respectively (Samorini, 2001).Depiction of a mushroom in shamanistic scene was found on Mount Bego, France dating at 1800 B.C. (Samorini, 2001).Some mushrooms have been known for their hallucinogenic effects and early humans used them in spiritual rituals.Fly agaric mushroom (Amanita muscaria) has a hallucinogenic effect but can be poisonous to humans (Figure 1).Many legends tell that the Vikings consumed before the battle these mushrooms to induce frenzy and fearlessness and be less sensitive to pain.The native peoples in pre-Columbian Mesoamerican societies used hallucinogenic species of the Psilocybe genus in group ceremonies for religious communion (Carod-Artal, 2015).Numerous so-called 'mushroom stones' (sculptures) dating from 1000 -500 years.B.C. were found in Mexico, Guatemala and Salvador testifying to the existence of mushroom cult in Mesoamerica.
Lingzhi, also known as reishi or Ganoderma is a mushroom tightly connected with Taoism.Taoist temples in ancient China were called "the abode of mushrooms", and Lingzhi, "spirits mushroom", used for a concentrated hallucinogenic decoction, was called "the mushroom of immortality".Some mushrooms possess toxicity; among the huge variety of existing mushrooms, about 100 species are poisonous to humans (Graeme, 2014;Li et al., 2021).
Mushrooms have an extremely varied size, shape and appearance; some of them are brightly colored, those belonging to Phallus indusiatus are wrapped in a transparent veil, and smell of the cap of Wood witch attracts flies and other insects (Figure 1).
For a long time, mushrooms were not grown, and they could only be collected from their natural habitats.And even today, only a small number of mushroom species are cultivated compared to the total number of edible species.In the modern world, there is an ever-increasing interest in mushrooms as a food product having certain health benefit properties.There are three main areas on the use of mushrooms, namely, wild edible, medicinal and commercially cultivated (Anusiya et al., 2021).

Wild mushrooms as food products
Wild edible mushrooms could serve as a source of ingredients for production of functional food.Mushrooms consist of the fruiting body (stalk, cap, and gills) and mycelium, a root-like structure.Gathering of wild mushrooms for using them for food has been done since ancient times.Fruit bodies of growing mushrooms make up a certain part of the diet of the poor in many rural areas around the world, and at the same time are a favorite delicacy of many gourmets.It was reported based on the current data over 100 countries that more than about 2,100 species of mushroom having different degrees of edibility exist in nature; however the number of them accepted as food does not exceed 25 (Barros et al., 2007;Pérez-Moreno et al., 2021;Zhang et al., 2013).The global market of wild edible fungi exceeded 1, 230,000 tons in 2017 estimated to be worth more than 5 billion USD (Pérez-Moreno et al., 2021).The harvesting of some wild mushrooms takes place on an especially large scale and has become now a really big business (Peintner et al., 2013).This is especially true for chanterelles (Cantharellus cibarius), morels (Morchella esculenta, M. deliciosa and M. elata), truffles (Tuber melanosporum and Tuber magnatum) and matsutake (Tricholoma matsutake) (Moore et al., 2020).Truffles, underground mushrooms, are especially appreciated by gourmets.In Europe, truffles are mainly collected in France and Italy.Previously, they were searched for with specially trained pigs, but now dogs are used for this purpose.Matsutake ("pine mushroom" in Japanese) has a unique taste and aroma and occupies a place in Japanese cuisine similar to the truffle in European cuisine.The price for these mushrooms is extremely high.The cost of truffles depends on season, weather factors (drought or rainfall) and of mushroom size; for example, the price of white truffles in 2022 was around 4,500 euros/kg (Trivelli Tartufi, 2023).A piece of matsutake, one of the most expensive mushrooms, which can only be harvested in the forest, their natural habitats, could be sold for more than 200 USD in the Tokyo market and its overall value is estimated as 4.6 to 7.7 billion USD annually (Moore et al., 2020).The annual world export market of collected chanterelles has been estimated at over 1.5 billion USD (Thorn et al., 2021;Watling, 1997).
It has been reported that the market of wild mushrooms is constantly increasing due to the decline of the traditional forest-based industries; gathering of this product in some countries are now considered as new sources of income (De Frutos Madrazo et al., 2012;Dejene et al., 2017;Román and Boa, 2006;Sileshi et al., 2023;Tibuhwa, 2013).The increased interest for forest mushrooms led to development of "mycosilviculture" aimed at improving productivity and profitability of forest stands, and consequently a better mushroom availability (Corona et al., 2016;Savoie and Largeteau, 2011;Tomao et al., 2017).
Composition of wild mushrooms.Species of wild mushrooms are diverse in taxonomic, ecological, and physiological features; they grow everywhere on a variety of flat and forest soils, and it is influenced, as expected, by local climatic conditions.Among the global mushroom industry, wild species account, according to their applications, for only 8%, while this number for cultivated and medicinal samples consists of 54 and 38%, respectively (Royse et al., 2017).Interestingly, edible wild mushrooms have a high nutritional value containing protein, fibers, essential fatty acids, vitamins, and trace minerals while having low energetic value and are cholesterol-free.
The composition of fruiting bodies of five species of the most popular wild edible mushrooms (Figure 2) are shown in Table 1.Body of the mushroom contains high levels of water, 86 -94 g/100 g, so the content of dry matter (DM) is very low.The range of the different compounds present in wild edible species growing in Central and Eastern Europe is extremely varied, in g/100 g DM: protein from 7.9 for Suillus granulatus (weeping bolete) to 56.3 for Agaricus arvensis (horse mushroom, snowball mushroom) and 80.9 for A. bisporus (button mushroom); fat from 0.3 for S. granulatus to 11.5 for Boletus edulis; ash from 3.5 for A. bisporus to 11.5 for Cantharellus cibarius (chanterelle), and carbohydrates from 8.3 for C. cibarius to 81.4 for S. granulatus.Boletus edulis (king mushroom, penny bun, porcino or porcini), one of the most famous edible mushrooms in many countries, contain protein, 27.2;fat, 2.8, and ash, 6.3 (Ouzouni and Riganakos, 2007).It was found that wild species are even richer by protein and have lower fat content in comparison with cultivated ones (Barros et al., 2008).Low energy value, allowed to use mushrooms in low-calorie diets (Barros et al., 2007;2008a, b;Beluhan and Ranogajec, 2011;Jaworska et al., 2015;Kalač, 2009;Ouzouni and Riganakos, 2007;Xu et al., 2019).
So, oleic, mono-unsaturated omega-9 fatty acid, and linoleic, polyunsaturated omega-6 fatty acid, were present in the highest amount in all mentioned above, wild mushrooms.This is consistent with the finding of Sande and co-authors (2019) who, based on reviewing the literature of Agaricus bisporus, Pleurotus ostreatus, and Boletus edulis mushroom species from different continents noted the predominant presence of the same fatty acids, but their quantitative composition varied significantly: linoleic acid ranges from 0.0-81.1%,oleic acid between 1.0 and 60.3%, and linolenic acid from 0.0-28.8%.
Vitamin D in wild mushrooms.It was shown that mushrooms are a good dietary source of vitamin D, which actively participates in regulation of calcium metabolism and needed to reduce the risk of osteomalacia in adults and rickets in children (Charoenngam et al., 2019).Recommended daily intake of this vitamin is 15 μg/day in Europe, USA, and Canada (Cardwell et al., 2018).
In wild mushrooms exposed to UV radiation, ergosterol present in the cell membrane is converted to D2, one of the forms of vitamin D. Bioavailability of vitamin D2 from mushrooms for humans was demonstrated by the results of clinical studies (Keegan et al., 2013;Mehrotra et al., 2014;Outila et al., 1999).The content of vitamin D2 in some wild mushrooms is shown in Table 4. Mushrooms from genera Cantharellus have a high amount of vitamin D2 (ranging from 10.7 to 21.1 µg /100 g FM) that is preserved after culinary treatment.Thus, the content of vitamin D2 in canned Cantharellus cibarius was 12.1 µg/100 g FM (Teichmann et al., 2007).King mushroom Boletus edulis could be a source of vitamin D2, meanwhile the content of D2 in mushrooms from the genera Agaricus is low (Teichmann et al., 2007).
Biological active substances in wild mushrooms.Wild mushrooms possess antioxidant activity due to the presence of such bioactive substances as flavonoids, phenolic compounds, tocopherols, ascorbic acid and carotenoids (β-carotene and lycopene) (Table 5).
Carbohydrates in wild mushrooms.Carbohydrates of mushrooms include mainly chitin, and also hemicellulose and glycogen.The presence of indigestible chitin apparently limits availability of the nutrients contained in mushrooms (Borthakur and Joshi, 2019) and causes the fact that people with diseases of the gastrointestinal tract are not recommended to consume mushrooms in significant quantities.However, chitin well absorbs toxins and heavy metals, removing them from the body during digestion.The active polysaccharides (βglucans) contained in mushrooms strengthen the immune system and are considered as a health-promoting factor.Due to the presence in mushrooms carbohydrates such as hemicellulose, chitin, α-and β-glucans, xylans, mannans and galactans also serve as a prebiotic (Jayachandran et al., 2017).It is considered that 100 g of mushrooms supply from 9 to 40% of the daily recommended allowance of dietary fiber (Manzi et al., 2001).Barros et al., 2008a   Boletus edulis (Poland) 1618 n. a n. a n. a n. a n. a Mineral elements in wild mushrooms.Usual content of major mineral elements in wild growing mushrooms is as follows, mg/100 g of dry matter: sodium, 10-40;potassium 2000-4000;calcium, 10-50;magnesium, 80-180;phosphorus, 500-1000;sulfur, 100-300 (Kalač, 2009).The accumulation of a wide variety of minor and trace elements in mushrooms is species-and site-dependent (Alaimo et al., 2019).Taking into account the ability of mushrooms to absorb heavy metals, especially mercury, lead, arsenic and cadmium, it should be noted that they can be collected only in noncontaminated places far from industrial areas (Nowakowski et al., 2021).
It should be noted that although mushrooms of the same species grow under similar conditions, for example chanterelles grow in coniferous forests in mossy areas or in birch forests, but their chemical composition may differ depending on the place of growth, soil and climatic features of the area, and time of harvesting.
Popular species of wild edible mushrooms growing in European forests are shown in Figure 3. Low sodium content, 10 -40 mg/100 g, in mushrooms independent of their habitat and taxonomic position (Na in whole milk 40-60 mg/100 g, and in meat products 1000-2200 mg/100 g) (Vetter, 2003) makes them advisable supplement to meat to decrease sodium intake (Guinard et al., 2016).Moreover, due to mushroom savory flavor their addition to any dish allows to diminish sodium content in the diet.The substitution of 80% of the meat with ground champignons (Agaricus bisporus) in the beef taco blend did enhance its overall flavor and allowed to reduce salt content by 25% (Myrdal Miller et al., 2014).
Use of wild mushrooms in food products.It is considered that mushrooms possess a unique taste called umami (Japanese word means "essence of deliciousness"), the fifth taste combining sweet, sour, salty and bitter, which is created by monosodium glutamate-like amino acids and 5'-nucleotides (Bernas, 2017;Zhang et al., 2013).Thus, it was estimated that mushrooms Agaricus bisporus contain about 370 mg of monosodium glutamate per 100 g of DM (Bernas, 2017).Therefore, by adding mushrooms to food products, three goals are achieved: increasing the nutritional value, giving the product an exquisite taste, and a certain medical positive effect.However, the cases of food allergy caused by consumption of different mushrooms have been reported (Ito et al., 2020;Kobayashi et al., 2019) and it is considered that around 1-3% of human population have allergy to mushrooms (Anusiya et al., 2021).
The use of edible wild mushrooms for food preparation in catering establishments, food for individual consumption is well known.But there is experience in the use of wild mushrooms in industrial food production.For example, Cantharellus cibarius grows from June to October in pine, birch, oak and hornbeam forests and has been used for food preparation in several European countries, Asia, America, and Africa.Only in Europe chanterelle mushrooms are collected for about 188,000 tons per year (Bulam et al., 2021).These mushrooms are used to supplement different dishes like omelets, soups, risotto, pizza, meat and fish dishes.It is a commercially important mushroom, which is present in the world market in fresh, dried, frozen and pickled state.
There are many special dishes from different countries using wild mushrooms.Examples of such dishes popular in European countries can be risotto made with wild mushrooms, a famous Italian dish; Slovak soup "kapustnica", prepared from sauerkraut, smoked meat, sausage, prunes, and mushrooms; Polish bigos (type of stew) made from sauerkraut, different meats, sausage, prune and dried or pickled wild mushrooms (Procházka et al., 2023;Weichselbaum et al., 2009).Fried mushrooms with onions, soup added with mushrooms, mushroom sauces are very popular dishes among Ukrainian population living in wooded areas (Luczaj et al., 2015), and application of wild mushrooms in different food products are appreciated in Lithuania and Germany.
Application of wild mushrooms in preparation of food products not only increases their biological value, but also serves to enhance their sensory properties like aroma and taste, and expands the shelf life of the final products.Cantharellus cibarius and Boletus edulis decoctions possess antioxidative and antimicrobial activity, and authors proposed to use them instead of the commercial antioxidants in preparation of frankfurters (Novakovic et al., 2019;2020).Frankfurter sausages prepared with addition of the decoction of the dry powdered mushrooms improve odor, taste, and overall quality of finished products and increase the shelf life under chilled storage due to reducing lipid oxidation several times compared with control.
Due to the popularity of mushrooms worldwide, it may be of interest to note that for a long time hallucinogenic mushrooms were sold in the streets of Amsterdam; but a ban on their sale was introduced on December 1, 2008 (Figure 4).

Wild mushrooms as pharmaceutical products
Wild edible mushrooms as well as cultivated ones possess different pharmaceutical properties including antidiabetic, antiallergic, antioxidative, antiviral, antibacterial, antifungal, immunomodulating, antidepressive, osteoprotective, nephroprotective, hypotensive and hepatoprotective activities and are used in the production of different pharmaceuticals (Anusiya et al., 2021;Thakur and Singh, 2013;Venturella et al., 2021).According to Gargano et al. (2017) mushrooms have more than 130 medicinal functions including also radical scavenging, cardiovascular, cholesterol-lowering, and detoxicative; drugs from mushrooms can be used as s painkillers and analgesics, as well as for prevention of immune disorders and improve quality of life in patients with various types of cancers or who are going under chemotherapy, patients with hepatitis B, C, and D and others.It is also suggested that bioactive compounds in mushrooms have shown neuroprotective effects on Alzheimer disease (Li et al., 2023).However, the pharmacological properties of medicinal mushrooms are studied mainly in vitro assays or in vivo using animal models, and there are only few clinical trials in humans showing positive effect of orally administered mushroom consumption on health state.So, we have focused only on proven cases of mushroom health benefits for humans.Crude extracts of the whole mushroom fruiting bodies or mycelia and isolated partially purified bioactive substances, for instance lentinan or polysaccharides, are more often used in medical studies (Table 5).It was reported that such species of mushrooms with anticancer properties as Lentinula edodes (22.2% from total studies), Coriolus versicolor, and Ganoderma lucidum (both 13.9%), followed by Agaricus bisporus (A.blazei and A. sylvaticus) and Grifola frondosa (both 11.1%) are more often used in the clinic studies (Panda et al., 2022).Among mushrooms with pharmacological activity there are such species as Agaricus blazei (royal sun Agaricus), Inonotus obliquus (chaga), and Ganoderma lucidum (reishi) (Frost, 2016).These mushrooms are proposed to be used as antitumor agents and immunomodulators (El Enshasy and Hatti-Kaul 2013;Gariboldi et al., 2023).
Agaricus mushroom preparations were studied in clinical trials and it was shown that they could be useful for treatment of patients with cancer to diminish adverse chemotherapyassociated side effects (Ahn et al., 2004;Valadares et al., 2013), and improve health status of patients with colorectal cancer (Fortes et al., 2008;2009).Agaricus blazei, native to Brazil, with a popular name as Cogumelo do Sol (sSun mushroom), or Himematsutake in Japan, is one of the more studied medicinal mushrooms.It was shown in randomized, blind, placebocontrolled clinical trials that preparation from A. blazei reduced chemotherapy-associated side effects by increasing appetite and emotional stability and diminishing alopecia and general weakness in gynecological cancer patients (Ahn et al., 2004).Dried extract of A. sylvaticus increased the immunity of patients with colorectal cancer (Fortes et al., 2008) and improved health status of postsurgical patients with colorectal cancer (Fortes et al., 2009); dietary supplementation with this mushroom (scaly wood mushroom) in form of dried extract reduced adverse side-effects of anticancer drugs improving gastrointestinal functions in patients with breast cancer treated with chemotherapy or radiotherapy (Valadares et al., 2013).Encapsulated extract from dried mushrooms Agaricus blazei increased insulin resistance in patients with type 2 diabetes (Hsu et al., 2007).
Inonotus obliquus (chaga, tinder fungus), is a black-brown mushroom that grows on damaged areas of deciduous trees more often on birches and less often on alder, ash, maple, rowan, beech, and elm, but only mushroom grown on birch has useful properties.This mushroom has been used in folk medicine from ancient times.Hippocrates described in the Hippocratic Corpus how to use infusions of this mushroom to wash wounds.And it was published in literature that Vladimir Monomakh, Grand prince of Kyiv, used this mushroom to treat himself for a lip tumor back in the 12th century (Szychowski et al., 2021).There are evidences that the fruiting bodies of I. obliquus have been employed in folk medicine in Eastern Europe in the 16 century (Lindequist et al., 2005) and has been used in the treatment of cardiovascular disease, gastrointestinal cancer, and diabetes mellitus until now (Duru et al., 2019).
Extracts from I. obliquus contain different biological active substances such as polysaccharides, polyphenols, triterpenoids, melanin, which have anticancer, antiinflammatory, antiviral, antiparasitic, antioxidant, immunomodulatory, hypoglycemic, hypolipidemic, hepatoprotective, antiviral, hypolipidemic and immunomodulatory activities, and have at the same time the therapeutic potential to counteract the progression of cancer and diabetes (Lu et al., 2021;Szychowski et al., 2020).However, until present there are only few clinical studies confirming the effectiveness of the use of this fungus for medical purposes.There are reports of two clinical trials made in Russia in 1973-1981(Frost, 2016)).It was shown that application of commercially produced extract from сhaga "Befungin" helps to normalize the health state of patients with psoriasis or peptic ulcers (Table 5).However, in case of peptic ulcers pain, which was relieved by taking the extract, returned to its previous level after stopping the intake.
Meanwhile, chaga mushrooms are widely used in pharmaceuticals.Despite the lack of controlled studies evaluating the safety of I. obliquus preparations from it, like many mushroom supplements, are produced mainly based on the experience of their long-term traditional use (Frost, 2016).The global market for chaga mushroom-based products is estimated at $ 25.8 billion USD in the year 2022, and it will probably reach $ 62.8 billion by 2030 (Report, 2013).
It should be noted that chaga is widely consumed not only as pharmaceutical, but also as herbal tea, syrup, bath agents, or concentrate (Duru et al., 2019).There are many reports of chaga beneficial health effects, but on the contrary there are some cases warning about the need to be careful when using chaga preparations as a pharmaceutical (Lee et al., 2020).
Ganoderma lucidum, wood-degrading basidiomycetes that can be found all over the world, is an edible medicinal mushroom known as Ling Zhi (the mushroom of immortality) in China and Korea, and reishi (the mushroom of spirituality) or Mannentake (10,000-yearold mushroom) in Japan.It has been known from ancient times in folk medicine of China, Japan and other Asian countries to treat stomach diseases, arthritis, and asthma.Studies conducted in vitro and in vivo showed its anti-inflammatory, antidiabetic, antiviral, and antibacterial activity and various other health benefits (Andrejč et al., 2022).At present, Ganoderma lucidum is one of the best studied species of medicinal mushroom.Description of reishi is included in the American Herbal Pharmacopoeia (AHP), and this mushroom is regulated as a dietary supplement in the United States (AHP, 2006).G. lucidum is included in the Pharmacopoeia of the People's Republic of China (2000) and approved for the treatment of dizziness, insomnia, palpitations, shortness of breath, cough and asthma (AHP, 2006).
G. lucidum contain about 400 different bioactive compounds (Ahmad, 2018), meanwhile triterpenes, polysaccharides, and peptidoglycans are three major groups of pharmacologically active constituents, which are present in different amounts in the fruiting bodies, mycelium and spores of reishi (Boh et al., 2007;Chan et al., 2021;Ferreira et al., 2015;Martínez-Montemayor et al., 2019).Preclinical studies showed that polysaccharides of this mushroom possess anti-tumor activity due to immunostimulating effects.Clinical study on humans indicated enhanced immune responses in advanced-stage cancer patients treated with 1,880 mg Ganopoly ® , the polysaccharide fraction extracted from G. lucidum, three times daily for 12 weeks (Guo et al., 2003a).The immunomodulating effects of Ganopoly ® taken 600 mg three times daily for 12 weeks by patients with advanced lung cancer was confirmed in a randomized double-blind, placebo-controlled clinical trial (Gao et al., 2003b).The authors concluded that Ganopoly ® may have an adjunct role in the treatment of patients with advanced lung cancer.The clinic study showed that patients with breast cancer undergoing endocrine therapy who took spore powder of G. lucidum 1000 mg three times a day for 4 weeks became less anxious and depressed than those from the control group who received placebo (Zhao et al., 2012).A randomized, double-blind and placebo-controlled study of the efficiency and safety of Ganopolyª in Chinese patients with neurasthenia showed the improvement of neurasthenia symptoms after 8 weeks treatment with 1800 mg three times a day orally (Tang et al., 2005).It was shown in the clinic study that patients with confirmed type 2 diabetes mellitus after receiving exactly the same treatment had lower blood glucose concentrations than those in the placebo group (Gao et al., 2004a).The double-blind, randomized clinical trials showed a decrease in blood pressure and serum cholesterol levels in patients with confirmed coronary heart disease receiving extracted G. lucidum polysaccharides (Ganopoly) for 12 weeks (Gao et al., 2004b).
Currently, a great diversity of commercial G. lucidum products are available in forms of powders, dietary supplements, and tea (Chan et al., 2021;Wachtel-Galor et al., 2011).The world trade market value of G. lucidum and its derivative products is estimated approximately 4 billion USD and includes over 100 brands (El Sheikha, 2022).Dietary supplements containing reishi or substances from this mushroom could be used to support conventional medicine, as it was demonstrated in various clinical trials, to treat different diseases including cancer.However, further studies for confirmation efficiency and safety of reishi use in medicine should be conducted.
Poria cocos (wolf or fuling), an edible mushroom, which is found all over the world, growing on the dead bark and roots of diverse species of Pinus trees (Li et al., 2019).It has been used as traditional Chinese medicine for more than two thousand years to treat a wide range of human diseases.The most active substance in Poria cocos is its polysaccharide fraction, which consists of up to 84% of dried sclerotium weight.Pharmacological effects of P. cocus polysaccharides were intensively studied in recent years and as a result a medicine preparation "Polysaccharidum of Poria cocos oral solution" was developed and received approval as a drug by Chinese Food and Drug Administration in 2015 (Li et al., 2019).This drug could be used as immune-therapeutics to treat patients with different types of cancers, hepatitis and other diseases, alone or combined with chemo-or radiation therapy for cancer treatment.It was also shown in 73 randomized clinical trials that including of Poria cocos to hypoglycemic agent-treatments patients with type 2 diabetes mellitus could benefit reducing their fasting blood glucose (Di et al., 2022).Authors suggested that additional, deeper and careful studies are pending.

Other mushrooms with pharmaceutical properties undergoing clinical trials include
Hericium erinaceus and Antrodia cinnamomea.H. erinaceus (Lion's mane mushrooms, yamabushitake) can be used for treatment of people with cognitive impairment.Terpenes and polysaccharides from this species stimulate the growth and differentiation of nerve cells and perform a protective function against exposure to oxidative stress.A double-blind, placebocontrolled clinical trial performed on 50-to 80-year-old Japanese men and women with mild cognitive impairment showed that intake of 250 mg tablets with 96% mushroom powder, three times a day, for 16 weeks improved patient's cognitive abilities (Mori et al., 2009).A. cinnamomea or A. camphorata is a very rare forest mushroom native to Taiwan that has been used as a traditional medicine for treatment of various human diseases including several types of tumor.However, human clinical trials to study the efficiency of A. cinnamomea as medicine are extremely limited.Advanced cancer patients receiving chemotherapy were administered with placebo or 20 mL of a mushroom aqueous extract daily for 30 days in a double-blind, randomized clinical study (Tsai et al., 2016).There was no improvement in the outcome of patients, except that the patients taken mushroom extract showed significantly better quality of sleep.
In another clinical study it was found the incidence decrease of adverse effects from chemotherapy among patients with advanced cancer who received orally dried Lentinula edodes mycelia extract, 1800 mg/day for 12 weeks (Okuno and Uno, 2011).
Among other medical mushrooms Grifola frondosa (hen-of-the-woods or maitake) is cited which an edible species is growing at the base of oaks or maples in Asia, Europe, and North America.Polysaccharides of its fruiting body and mycelium includes β-glucans and heteroglycans, and extracts of this mushroom demonstrated antitumor and immunomodulatory effects in preclinical studies.An increase in immune activity was observed in patients with breast cancer who took maitake liquid extract 5-7 mg/kg orally twice a day for 3 weeks (Deng et al., 2009).
Mushrooms contain many biologically active compounds, and a lot of modern studies are devoted to the isolation, study of properties and the possibility of using such substances in medicine, and they accounts for not less than 130 medical functions (Gargano et al., 2017).Polysaccharides, among these compounds, play outstanding functions with antitumor and immunomodulating activities which have been proven in clinical studies.It was demonstrated, for instance, for purified β-glucan lentinan, isolated from Lentinula edodes (shiitake mushroom), its successful application in the combined treatment of cancer diseases in Japan.It was shown, in randomized controlled clinical trials, that advanced gastric cancer patients treated with chemotherapy and lentinan had a much longer survival time compared to patients treated only with chemotherapy (Oba et al., 2009).
A serious drawback in the use of mushrooms for medical purposes is the lack of regulations, standards and protocols for their certified elaboration production and strict testing of mushroom products.This may be the main reason why commercial mushroom products change in composition and consequently in effectivity; even the active components of many commercial mushroom products have not yet been identified (Wasser, 2010(Wasser, , 2011)).The latter item is one of the challenges for a more efficient and safety use of mushrooms in medicine.
On the other hand, more and more attention has been recently paid for studying the potential use of mushrooms to prevent Alzheimer's disease (AD) or slow down its symptoms in patients who have been already suffering from AD (Li et al., 2023;Silva et al., 2023).A lot of clinical trials have shown that dietary factors are extremely important in treating and preventing Alzheimer's disease (Bello-Corral et al., 2021;Stefaniak et al., 2022;Yusufov et al., 2017).Results of 10, out of 12, clinical studies demonstrated a protective effect of the Mediterranean plant-based diet on the risk of developing AD.It is believed that to reduce the risk factor for developing this disease, the diet should contain substances with neuroprotective properties, such as antioxidants, B vitamins and polyunsaturated fatty acids, which are present in mushrooms.In addition, these species contain a large number of biologically active compounds involved in mechanisms associated with AD including the potent antioxidants ergothioneine and glutathione as well as vitamin D, which may have neuroprotective properties.In people with mild cognitive impairment being potentially vulnerable to dementia reduced levels of ergothioneine, an unusual thio-histidine betaine amino acid, have been observed (Cheah et al., 2016).Ergothioneine is contained in mushroom fruiting bodies, where it is typically the main antioxidant; it has been found and quantified in various wild and cultivated mushrooms.The highest amounts of ergothioneine is reported in Pleurotus ostreatus (oyster), 2.59 mg/g DM, but it was found, mg/g DM, in Lentinula edodes (shiitake), 1.98; Grifola frondosa (maitake), 1.13; Agaricus bisporus (white button), 0.21 (Dubost et al., 2007); Ganoderma lucidum (reishi), 0.56; Hericium erinaceus (lion's mane mushroom), 1.12; Boletus edulis (porcini), 7.27; Cantharellus cibarius (chanterelle), 0.20; and Morchella esculenta (morel), 0.47 (Kalaras et al., 2017).In brief, it is considered that increased ergothioneine intake including mushrooms in the diet might possibly promote cognitive health (Feng et al., 2019).
Most studies regarding certain substances found in mushrooms were carried out in vitro and on animals, but there are also results from clinical studies on humans.For example, Termitomyces species, the termite mushrooms, contain cerebrosides, which are known to have an important role in the treatment of neurodegenerative disorders including AD (Paloi et al., 2023).Erinacine A, cyathin diterpenoid, a compound present in Hericium erinaceus (lion's mane mushroom) was evaluated in clinical trials to relieve AD symptoms and showed neurotrophic and neuroprotective activities (Li et al., 2020).
There are some clinical trials that prove beneficial role of mushroom consumption in improving cognitive performance.The cohort study involving 13,230 elderly Japanese people aged over 65 years showed that frequent consumption of mushrooms (3 times per week or more) reduced by 19% the risk of incident dementia (Zhang et al., 2017).The same finding that mushroom consumption may serve as a preventive measure to slow down neurodegeneration with aging was made by Singaporean researchers, who studied for more than 6 years the association between mushroom consumption and mild cognitive impairment based on data from 663 participants aged 60 years and older (Feng et al., 2019).An analysis of data from U.S. people over 60 years of age found that mushroom consumption is associated with cognitive performance, and if it is consumed in large amounts may reduce the risk of cognitive decline (Ba et al., 2022).Thus, regular intake of mushrooms is a way to potentially reduce the risk of neurodegenerative disorders.

Wild mushrooms as industrial products
Industrial cultivated edible mushrooms are very popular as food products (Rangel-Vargas et al., 2021) widely used for preparation of medicinal drugs (Valverde et al., 2015), and constantly increasing all over the world.Thus, world production of mushrooms has increased more than 30-fold since 1978 (Royse et al., 2017).Total production of mushrooms and truffles worldwide from 2012 to 2021 augmented from 31.78 to 44.21 million metric tons (Statista, 2023); China is a leading country producing about 75% of the word's mushrooms and is the world's largest producer of Flammulina velutipes (Royse et al., 2017).The most cultivated edible mushroom genera are Lentinula which covers about 22% of the world's production followed by Pleurotus, 19% of the world's output; Auricularia, 18%; Agaricus, 15%; Flammulina, 11%; Volvariella, 5%; and others, 10% (Royse et al., 2017) (Figure 5).Pleurotus ostreatus (oyster mushroom), Agaricus campestris, and Agaricus bisporus (button mushroom) are cultivated all over the world, while Lentinula edodes (former Lentinus edodes) (shiitake), Auricularia auricula (wood-ear or tree ear), Volvariella volvacea (edible straw mushroom), Flammulina velutipes (winter mushroom) and Ganoderma lucidum (red reishi) are cultivated mainly in (Stabnikova et al., 2008).Nowadays the mushroom production on a large scale is going in a form of so called solid state fermentation.However, there are two traditional methods, which are still used to harvest mushrooms: (a) cultivation on wood logs and (b) on compost.
Traditional methods used for mushroom cultivation.According to Japanese and Chinese traditions, Lentinula edodes (shiitake) was grown on shii (Castanopsis cuspidata) logs until the mid-1980s.Growth of shiitake on trees requires from one to two years before the first crop of fruiting bodies could be harvested.It is possible to expedite the growth of shiitake by growing the mushrooms aseptically in plastic bags or in trays on sterilized substrate containing saw dust, bagasse, straw, paper chips and supplemented with nutrients such as starch, yeast, sugars and protein (Figure 6a).Application of this method allows their harvesting in three-four months after inoculation; the residual compost could be used as a soil fertilizer (Stabnikova et al., 2008).
The composition of medium for shiitake cultivation could be different, but the basis of the substrate should be hardwood chips and sawdust and/or cereal straw.To increase the nutritional value, medium is supplemented with bran or grain, straw of cereals, waste from the food industry and agriculture.2-3 mm is an optimal particle size of sawdust and shavings of hardwood trees, and cereal straw is crushed to a size of 1-2 cm.Chalk or gypsum is added to improve the physical properties of the substrate.Cultivation is carried out in special chambers with the maintenance of desirable microclimate under sterile conditions or in conditions of a high degree of purity.Under the cited conditions, a yield of fruiting bodies from 15 to 30-50% from the weight of used substrate may be obtained.
Pleurotus (oyster mushroom) are much easily cultivated and the corresponding costs are lower compared to others mushroom species because these mushrooms have a shortest time to produce fruit bodies; additionally they can be grown using various lignocellulosic agricultural wastes due to their ability to produce enzyme laccase, which plays a key role in lignin degradation (Li et al., 2022).Using different waste products as substrate for cultivation of oyster mushroom species (Pleurotus ostreatus, P. cystidiosus, P. pulmonarius) allows to reduce their price to a reasonable level.It was reported that oyster mushrooms can be grown on sawdust, wood chips, cereal straw, banana leaves, peanut hull, corn leaves, wheat and rice straw, mango fruits and seeds, sugarcane leaves, hazelnut branches and husk, rice husk, spent coffee grounds, coffee pulp, grass, weed plants, olive cake, tomato tuff, pine needles, and cotton wastes (Akcay et al., 2023;Das et al., 2007;Hernández et al., 2003;Jatwa et al., 2016;Li et al., 2022;Raman et al., 2020).For instance, lignocellulosic biomass mixture from grounded leaves of date palms (Phoenix dactylifera), wheat straw, saw dust, and boobialla (Myoporum serratum) supplemented with wheat bran and corn meal at 5% of the substrate dry weight and gypsum, 5% (Alananbeh et al., 2014).Oyster cultivation is conducted in plastic bags (Figure 6b) or trays.
Different species of Pleurotus can grow under different temperature conditions using pasteurized composed substrate or sterile non-composted one, meanwhile their fruiting bodies are relatively rarely exposed to diseases or pests.However, Pleurotus fruit bodies have short life that makes them less competitive than Agaricus bisporus and Lentinula edodes (shiitake) (Raman et al., 2020).After harvesting of oyster mushroom fruiting bodies, "spent compost" could be used as soil conditioner to enhance soil structure; biofertilizer; animal feed due to enrichment composting material with protein by mushroom mycelium, or to use in bioremediation of soil polluted with toxic organic substances (Moore et al., 2020;Sadiq et al., 2019).Because Pleurotus has the ability for easy accumulation of heavy metals, only waste free from this contaminant could be used in mushroom production.
Auricularia auricular has different common names such as black fungus due to its dark brown to black color and wood ear or ear mushroom because of its shape.In nature this mushroom grows mainly on deciduous older trees or dead and decaying branches.It is currently the third most produced mushroom in the world and is widely cultivated in Asian countries for food and medicinal applications.China is a major producer of A. auricular, which accounts for more than 90% of the total global production and amounted 7 018 million tons in 2019 (Hao et al., 2022;Zhao et al., 2019).
This fungus possesses cellulases, xylanase, laccase and polyphenol oxidase enzymatic activity, so it is able to decompose lignin and cellulose and can be grown on lignin containing agricultural wastes.So, methods of its cultivation using compost to produce fruit bodies for food is similar to Pleurotus ostreatus.Major advantage is that cultivation of A. auricular could be done using submerged fermentation on simple liquid media for further isolation of medicinal valuable substances (Sun et al., 2016).
Cultivation of wild mushrooms in Europe was started in the 1600s when growers in Paris grew species known as Agaricus bisporus in fields, but the European mushroom industry started in the limestone caves beneath Paris at the end of the nineteenth century.This underground mushroom cultivation method has been used until our days.
Cultivation of mushrooms includes two major steps: preparation of the compost or solid medium and mycelium growth until fructification.For production of compost or medium for mushrooms cultivation, different organic and lignocellulosic materials can be used, such as wood chips, sawdust, hay, maize waste, paddy straw, cassava bagasse, waste paper, cotton seed hulls, water hyacinth, apple pomace, grape pomace oil palm bunch, husk rice, banana leaves cheese whey, horse manure, chicken manure, and others (Ivanov et al., 2021;Moore et al., 2020;Stabnikova et al., 2008).
Button mushrooms A. bisporus is one of the most cultivated species in the world, and it is the dominant fungus cultivated in Europe.In the USA, about 98% of the mushroom production comes from button mushrooms.The fruit bodies of white button of this mushroom are produced in large amounts for human consumption on a medium consisting of wheat straw, straw-bedded horse manure, chicken manure and gypsum (Straatsma et al., 2000).The materials are mixed, the ingredients are wetted, and composted for 8-9 days while temperatures will rise to 80°C during the period of uncontrolled self-heating.Then compost is packed in boxes and pasteurized for 8 h at 56-60°C and continues at 45°C for up to 7 days to remove volatile NH3 and to produce pathogen free substrate.After inoculation, compost is covered with a mixture of soil, peat, and chalk.The optimal temperature for mycelium growth is 24•C, and the optimal temperature for fruiting body production is from 14 to 18•C.The yield of mushrooms consists of around 1 kg from 1 kg of compost dry matter.Composition of compost could be changed depending on local availability of casing materials (Baysal et al., 2007).
Volvariella volvacea (paddy straw mushroom) also known as Chinese mushroom is also one of the most cultivated mushrooms of the world.It is grown mainly on rice straw, although other agricultural waste could be used.Generally, it prefers substrates with high content of cellulose and low content of lignin.Among the plant materials used for V. volvacea cultivation there are water hyacinth, oil palm bunch and pericarp waste, banana leaves, saw dust, cotton waste, and sugarcane bagasse (Ahlawat & Bindvi, 2016).Paddy straw is tied into bundles and immersed in water for 24 -48 h.After removing excess water the straw is piled into heaps which are inoculated with V. volvacea pure cultures or spent compost from previous mushroom cultivation.The first crop of egg-like sporophores could be harvested in less than 1 month.The main disadvantage of V. volvacea production is very short shelf life even in cold storage because of autolysis.These mushrooms could be stored just for 3 days at 10 -15 o C. Therefore, straw mushrooms are best used in canned, pickled or dried form.
Ganoderma lucidum, a wood-destroying mushroom, having different pharmaceutical properties, is grown primarily for medicinal use, not as food.The common method for its cultivation is provided on wood logs or sawdust or wheat straw added with wheat bran, tea leaves and cotton husk in plastic bags or bottles.For cultivation on sawdust, addition of sucrose, 1%, and calcium carbonate, 1%, is recommended.For cultivation on wood, short pieces of wooden logs (15 cm or less in diameter and 15-24 cm in length) with moisture content of 35-40% are inoculated with mushroom mycelium, covered with soil, and then with chopped straw to ensure needed moisture and temperature.Short-log cultivation takes 4-5 months for mycelial incubation and fruiting bodies are harvested approximately after 25 days from primordia formation (Boh et al., 2007).Modern biotechnology gives the opportunity to produce mycelium biomass by their submerged cultivation in bioreactors.Cultivation of G. lucidum in synthetic liquid media is proposed for production of different valuable substances for medical use (Abdullah et al., 2020;Supramani et al., 2023;Zhao et al., 2011).
Flammulina velutipes, commonly known as golden needle mushroom or winter mushroom, is wood decaying mushroom growing in nature on the stumps of the Chinese hackberry tree, called enoki in Japanese, but also on some other trees such as aspens, willows, elms, mulberry and persimmon.Wild species have a brown color and short stem, while artificially grown ones are white with long thin stems.F. velutipes is the fifth largest edible mushroom in global production, which is especially popular in Asian countries, China, Japan, Republic of Korea, and Taiwan.F. velutipes could be cultivated on wood logs or on sawdust added with rice or wheat bran in polypropylene bags or plastic bottles (Harith et al., 2014;Sengar et al., 2019).
Solid-state and submerged liquid cultivation of mushrooms.Nowadays, for mushroom cultivation in industrial scale solid-state and submerged liquid fermentations could be used.Solid-state fermentation (SSF) involves the growth of mushrooms on a solid substrate, mainly an agro-industrial waste, meanwhile submerged cultivation is the growth of mushrooms in a liquid medium with dissolved nutrients under agitation and air supply.Application of solid substrate with low moisture content is advisable to produce mushroom fruit bodies for food or medicine, meanwhile cultivation of mushrooms in liquid media in bioreactors is a promising way to obtain mycelial biomass as an animal feed or for the production of metabolites (Letti et al., 2018).
SSF has such advantages as possibility of using a wide range of agro-industrial wastes as substrates for mushroom cultivation, relatively low energy consumption because of a lack of mechanical agitation/mixing and aeration, use of a residual substrate for bioremediation, animal feed, biofuel production, and biosynthesis of mushroom metabolites.However, when fermentation is carried out on a large scale, it is not so difficult but expensive to control the parameters of the cultivation process, such as pH, moisture content, homogeneity of substrate, concentration of oxygen, heat and mass transfer, and in addition, there is the possibility of contamination.On the other hand, SSF could be successfully used for production of certain biological active substances, for example, lignocellulolytic enzymes (Wang et al., 2019).Thus, the efficiency of SSF for the production of enzymes such as laccases, among others, is evident due to their wide industrial and technological applications; these SSF enzymatic potentialities may catalyze the oxidation of various phenolic compounds and a number of aromatic amines during the production of edible mushrooms of the genera Pleurotus (Han et al., 2020) or Ganoderma (Postemsky et al., 2017;Sharma et al., 2019).
Meanwhile, submerged cultivation is a very effective way to produce mushrooms in the form of mycelium biomass, especially for manufacturing of different valuable substances with health benefits.Liquid cultivation of mushrooms gives opportunity to control the fermentation process and final product quality and avoid contamination.The process takes place under a sterile environment in liquid medium at conditions optimal for the growth of selected mushrooms such as temperature, pH, mixing, and level of aeration (Bakratsas et al., 2021).Among the advantages of using submerged fermentation is the possibility of obtaining mushroom biomass or high-value bioactive substances in a short cultivation time for largescale industrial applications.There are research studies devoted to production of truffles biomass using submerged fermentation, which is a promising way for business of this fungus (Tang et al., 2015).Application of liquid fermentation was proposed to produce bioactive metabolites such as triterpenoids, polysaccharides, antrodin, from medicinal mushroom Antrodia cinnamomea (Zhang et al., 2019).Cultivation of Auricularia auricular by this type of was proposed for melanin production (Sun et al., 2016).To synthesize exopolysaccharides by mycelial culture of Inonotus obliquus has also been done in liquid agitated conditions (Xiang et al., 2012).
Submerged mushroom cultivation is possible to use for production of mycoproteins, which possess high nutritional value and can be used in manufacturing of functional foods, for example in meat analogues production.Thus, cultivation of edible mushroom Pleurotus ostreatus LGAM was conducted in a stirred-tank bioreactor using aspen wood chips hydrolysate.The specific growth rate of mushroom was 1.8±0.4d −1 , biomass concentration was 25.0±3.4g/l, and protein yield consisted of 54.5 g per 100 g of sugars (Bakratsas et al., 2023).
Unusual method for mushroom cultivation.An interesting and unusual method is used to grow edible mushrooms of Ustilago maydis (huitlacoche or cuitlacoche) in Mexico and in some areas of Central America, where it has been traditionally produced, and of the USA, where huitlacoche has been recently used, as human food.There are clear evidences in different regions of Mexico that this fungus was in the common diet of the pre-Hispanic population.The maize, Zea mays, smut termed huitlacoche is characterized by the formation of galls or tumors in maize ears (Figure 7).Ear galls are considered an edible delicacy produced by the natural infection of the maize ears with the fungus Ustilago maydis.These smut galls are also called as maize mushrooms, Mexican truffles, or maizteca mushrooms and serve as an important food source in this country.Nowadays huitlacoche is a culinary delight for international chefs in selected places in the USA, France, Spain, Japan and others.In addition to its unique flavor, huitlacoche has been identified as a high-quality functional food and could be included into the daily diet for its attractive characteristics, selected nutrients, valuable compounds, and nutraceutical potential.

Conclusions
The role that the mushroom kingdom plays in human life is remarkable, and at the same time very important to be assessed.Simultaneously with the development of humanity, the function of mushrooms in human life has intensified and expanded.It started in the initial historical times, before the beginning of agriculture, as an additional source of nutrition, to become in the last decades as the object of large-scale industrial production using modern biotechnological procedures.The participation of mushrooms in human consumption and treatment has evolved from their use by healers and shamans to serious and careful clinical trials.
Wild edible mushrooms have a high nutritional value containing high-quality proteins, fibers, essential fatty acids, vitamins including D2, trace minerals, and such valuable compounds as polyphenols, terpenoids, sterols, while having low energetic value that allows them to be used in low-calorie diets.
Wild edible mushrooms contain many bioactive nutraceutical compounds and possess different specific pharmaceutical properties, which can be used in treatment of various serious diseases.However, more clinical trials on humans showing positive effect of orally administered mushroom consumption on health state are needed as well as regulations for food supplements with mushrooms, standards and protocols for the production and testing of mushroom products in general.
The gathering and use of wild edible mushrooms for food make a significant contribution to both the solution of the global food shortage crisis and economics of different countries around the world, and could be considered in some countries as new sources of income for local people.
The increase of interest on fungus consumption along human history at worldwide level has led to the development of basic and sophisticated techniques for their cultivation.Solidstate and submerged liquid fermentations are nowadays useful methods for cultivation of mushroom in a large-scale for their production including volumes of biomass and of very valuable specific bioactive metabolites.In brief, nowadays wild and cultivated procedures for the small and large scale production of mushrooms, and of fungal metabolites are playing, and much more will do it in the near future, outstanding roles in the use of raw materials and in the economy of populations of local people around the world; food, and pharmaceutical products and including industrial uses are their fields of utmost influence.

Figure 4 .
Figure 4. Hallucinogenic mushrooms in the streets of Amsterdam.
Figure 6.Shiitake (A) and oysters (B) cultivation in plastic bags

Figure 7 .
Figure 7. Ustilago maydis is responsible for corn smut: A, maize plant; B, maize cob; c, maize infected by U. maydis; D, formation of galls of tumors

Table 5 Total bioactive compounds of wild mushrooms Mushroom species
Barros et al, 2008c

Table 5 Results of clinical trials of mushroom application for medical purposes
*Ganopoly ® , mushroom polysaccharides