Wild and cultivated mushrooms as food, pharmaceutical and industrial products

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).

Table 5

Results of clinical trials of mushroom application for medical purposes

*Ganopoly®, mushroom polysaccharides

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 chemotherapy- associated 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, placebo- controlled 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 ^aga “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-year- old 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 (Andrejc 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; Martinez-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 Ganopoly2 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, placebo- controlled 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 p-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 function...