Effect of the Lingzi or Reishi Medicinal Mushroom Ganoderma lucidum (Agaricomycetes) on Hyperglycemia and Dyslipidemia with Experimental Metabolic Syndrome.

The effect of Ganoderma lucidum hot water extract of submerged cultivated mycelium suspensia on carbohydrate metabolism and lipid profile during fructose-induced metabolic syndrome in rats was studied. The outbred white male Wistar rats, in which metabolic syndrome was induced by consuming a 10% fructose solution instead of drinking water for 42 days, were used. After the induction of metabolic syndrome, the mycelium of G. lucidum in the form of water suspension (a dose of 1 g/kg of the animal's body weight) was administered to animals per os for 7 and 14 days. Glucose concentration was determined using the glucose oxidase method. The content of glycosylated hemoglobin in erythrocytes was determined by the colorimetric method. The concentration of triglycerides, cholesterol, high-density lipoproteins, and low-density lipoproteins in blood plasma was determined by enzymatic methods. A significant decrease in the content of glycosylated hemoglobin was established in animals with metabolic syndrome against the background of administration of the studied suspension. Under the conditions of experimental metabolic syndrome, the administration of mycelium for 7 and 14 days led to a decrease in the concentration of triglycerides by 17.8 and 44.8%, cholesterol by 10.7 and 21.3%, low-density lipoproteins by 14.8 and 28.4%, and to an increase in high-density lipoproteins concentration by 11.9 and 21.5%, compared with metabolic syndrome. The obtained results demonstrate the corrective effect of the suspension of the G. lucidum powdered mycelium on carbohydrate and lipid metabolism, which was directly proportional to the duration of administration.

Antioxidant Activities of Hot Water Extracts from Mycelial Biomass of Different Combinations of Medicinal Agaricomycetes Mushrooms.

This study aimed to determine the free radical scavenging and antioxidant potential of hot water extracts prepared from different combinations and ratios of submerged cultivated mycelial biomass of medicinal mushrooms. Total phenolic compounds, flavonoid content, and antioxidant activity were evaluated for combined crude hot water extracts from medicinal higher Basidiomycetes mushrooms belonging to ten genera. The results demonstrate that almost all tested combinations were good sources of phenolic compounds and flavonoids, ranging between 16.42 and 18.83 gallic acid equivalents/g and 1.5 and 4.34 mg rutin equivalents/g, respectively. Moreover, free radical scavenging properties were evaluated with the DPPH and ABTS assays and metal chelating effects were investigated. All tested samples and/or extracts demonstrated significant free radical scavenging properties and antioxidant potential.

Chemical Composition and Antioxidant Properties of Different Combinations of Submerged Cultured Mycelia of Medicinal Mushrooms.

This research describes the investigation of submerged cultivated mycelial biomass and hot water extracts prepared from different combinations and ratios of medicinal mushroom (MM) dry powders, comprising various biologically active compounds/secondary metabolites. In particular, it was evaluated the proximate composition (moisture, ash, crude protein, fat, total carbohydrates, and total energy), γ-aminobutyric acid (GABA) and ergothioneine (ERG), amino acid content of mycelia of 16 higher Basidiomycetes MM species. The results obtained demonstrate that almost all tested combinations were found to be good sources of polysaccharides, with content varying in the ranges of 4.73 ± 1.33% and 58.46 ± 4.15%. Total protein contents varied in 1.97 ± 0.40% - 5.37 ± 0.40% range. ERG was detected in all tested samples, while GABA existed only in eight samples out of 15 and varied from 0.03 ± < 0.01 to 0.61 ± 0.03 mg/g, and from 0.16 ± 0.03 to 5.69 ± 0.41 mg/g respectively. Analyses of total phenolic and flavonoid contents demonstrate considerable content in all samples (15.53 ± 0.23 - 18.88 ± 0.34 mg gallic acid equivalents/g and 1.23 ± 0.04 - 4.34 ± 0.73 mg rutin equivalents/g respectively). In present research the complexity of samples/extracts were evaluated by multiple antioxidant assays to verify their antioxidant capacity. Determination of in vitro antioxidant activity was successfully carried out by several different methods such as 2,2-diphenyl-1-picrylhydrazyl scavenging activity, reducing power, chelating ability, hydroxyl radical scavenging activity, and 2,2'-azino-bis(3-ethylbenzothi-azoline-6-sulfonic acid scavenging activity. Therefore, all tested samples confirm the capable antioxidant activities of bioactive compounds extracted from MMs.

Medicinal Mushrooms against Influenza Viruses.

This review provides results obtained by scientists from different countries on the antiviral activity of medicinal mushrooms against influenza viruses that can cause pandemics. Currently, the search for antiviral compounds is relevant in connection with the coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Medicinal mushrooms contain biologically active compounds (polysaccharides, proteins, terpenes, melanins, etc.) that exhibit an antiviral effect. The authors present the work carried out at the State Research Center of Virology and Biotechnology Vector in Russia, whose mission is to protect the population from biological threats. The research center possesses a collection of numerous pathogenic viruses, which allowed screening of water extracts, polysaccharides, and melanins from fruit bodies and fungal cultures. The results of investigations on different subtypes of influenza virus are presented, and special attention is paid to Inonotus obliquus (chaga mushroom). Compounds produced from this mushroom are characterized by the widest range of antiviral activity. Comparative data are presented on the antiviral activity of melanin from natural I. obliquus and submerged biomass of an effective strain isolated in culture against the pandemic strain of influenza virus A/California/07/09 (H1N1 pdm09).

Botanical drugs and supplements affecting the immune response in the time of COVID-19: Implications for research and clinical practice.

In times of health crisis, including the current COVID-19 pandemic, the potential benefit of botanical drugs and supplements emerges as a focus of attention, although controversial efficacy claims are rightly a concern. Phytotherapy has an established role in everyday self-care and health care, but, since botanical preparations contain many chemical constituents rather than single compounds, challenges arise in demonstrating efficacy and safety. However, there is ample traditional, empirical, and clinical evidence that botanicals can offer some protection and alleviation of disease symptoms as well as promoting general well-being. Newly emerging viral infections, specifically COVID-19, represent a unique challenge in their novelty and absence of established antiviral treatment or immunization. We discuss here the roles and limitations of phytotherapy in helping to prevent and address viral infections, especially regarding their effects on immune response. Botanicals with a documented immunomodulatory, immunostimulatory, and antiinflammatory effects include adaptogens, Boswellia spp., Curcuma longa, Echinacea spp., Glycyrrhiza spp., medicinal fungi, Pelargonium sidoides, salicylate-yielding herbs, and Sambucus spp. We further provide a clinical perspective on applications and safety of these herbs in prevention, onset, progression, and convalescence from respiratory viral infections.

Caterpillar Medicinal Mushroom, Cordyceps militaris (Ascomycetes), Mycelia Attenuates Doxorubicin-Induced Oxidative Stress and Upregulates Krebs Cycle Dehydrogenases Activity and ATP Level in Rat Brain.

Post-chemotherapy-induced cognitive dysfunction remains one of the challenges in cancer survivors. Cytokine-induced neurotoxicity manifests in subjects at any time after doxorubicin (DOX) chemotherapy. We examined the effect of bioactive Cordyceps militaris mycelia extract (CM) on the energy status, oxidative stress, and acetylcholinesterase activity in the brain of DOX treated rats. The CM (150 and 300 mg/kg b.w.) and DL-α lipoic acid (LA, 100 mg/kg b.w) were administered orally once daily for 5 days to male Wistar rats prior to the DOX administration (18 mg/kg as 3 doses of 6 mg/kg, i.p. b.w.) and continued for 6 more days. Cellular antioxidant status, Krebs cycle dehydrogenases, electron transport chain complexes (ETC) (I, III, and IV), adenosine triphosphate (ATP) level, advanced oxidation of protein products (AOPP), and acetylcholinesterase (AchE) activities were determined in the brain homogenate. The DOX alone treated group of animals showed significant decrease (p < 0.05) of brain antioxidant levels, Krebs cycle dehydrogenases activities, ETC complex activities, and decreased ATP level, while lipid peroxidation and AOPP levels were elevated. CM at 300 mg/kg b.w. or LA at 100 mg/kg b.w. elevated antioxidant status, Krebs cycle dehydrogenases, and complex activities and thus alleviated the toxicity. CM also inhibited the AchE activity in brain. The experimental results thus reveal that CM possessed excellent capacity to attenuate oxidative stress, upregulate respiratory chain complex activity and ATP levels, as well as inhibition of AchE activity.

Antioxidant Activities of Selected Medicinal Mushroom Submerged Cultivated Mycelia.

Medicinal mushrooms fruiting bodies have been used as food or medicine for years but cultured mycelium is faster to grow and costs less. This research studied the antioxidant activities of three species (five strains) of medicinal mushroom mycelia (Cordyceps militaris, Ganoderma tsugae I and II, Trametes versicolor I and II). Two-stage extractions were performed: first the sample was extracted with 70% ethanol, and then the residue was extracted with 95°C hot water. Both ethanolic and hot water extracts showed effective concentration (EC50) values of 0.29-4.22 mg/mL, indicating that these extracts were remarkably effective in antioxidant activities. The ethanolic extracts displayed more effective reducing power, scavenging, and chelating ability (EC50 0.33-2.37 mg/mL) than hot water extracts (EC50 0.58-4.22 mg/g). Besides, ethanolic extracts contained higher total phenol content (75.49-144.99 GAE mg/g) than the hot water extracts (22.77-58.68 GAE mg/g). Furthermore, the ethanolic extracts contained flavonoids but not the hot water extract. Overall, these mycelia were highly effective in the antioxidant activities and might be potent antioxidants.

Professor Shu-Ting Chang on His 90th Birthday.

This issue is dedicated to the 90th birthday of Professor Shu-Ting Chang, a prominent scientist in the field of mushroom biology, including cultivation and nutritional values of mushrooms, medicinal mushroom science, and environmental impact of mushrooms. Professor Shu-Ting Chang is also one of the initiators and has been an editor of our journal from its inception (in 1999) until now.

Professor Shu-Ting Chang, Cancer Mycotherapy and Le Chatelier Principle.

In the jubilee paper devoted to Professor Shu-Ting Chang, we aimed to outline the applicability of the Le Chatelier principle to various fields, especially to cancer biology and immunotherapy of malignant neoplasms. Cancer progression has been shown to be associated with a response to cell stress and survival agents. It was proclaimed that cancer immunotherapy, using fungal metabolites, should be carried out as a mode of compensation for imbalances that arise during the basic treatment. The challenges of immunotherapy in recent years have also received mention.

Profiles of Little-Known Medicinal Polypores: Haploporus odorus (Agaricomycetes).

The purpose of this study was to compile a comprehensive characterization of little-known polypores, which have recently been found to possess anticancer activity and thus can also be used in cancer target therapy. Haploporus odorus is a polypore of Holarctic distribution and has been found by harvesters working in taiga floodlands and broadleaf forests of the Northern Hemisphere. A substance known as haploporic acid A was determined in methylene chloride extract from the dried basidiomata of H. odorus. This substance can be used in cancer therapy; more details of its health benefits could be used in mycotherapy.

Cancer without Pharmacological Illusions and a Niche for Mycotherapy (Review).

In this review we outline a framework in which mycotherapy is effective in the field of oncology. We suppose that irreversible epigenomic changes in cancer cells and achieving their replicative immortality when cancer-specific targets are absent should take away any illusions about a fundamental possibility of pharmacological blockage of the cancer process once ontogenesis begins. At the same time, however, we believe that effects of both traditional and alternative medicines on cancer clonogenic units within a particular range can lead to prolonged remission; with this in mind, we carefully consider the various possibilities of mycotherapy in controlling cancer activity. The aforementioned range is limited to nondisseminated cancer processes and depends on the absence of large secondary tumor nodes and the inexhaustibility of immune depots after chemotherapeutic treatment. The main therapeutic effect of fungal bioactive complexes is dectin-1-mediated immunity, including the reprogramming of dendritic cells, which significantly increases the period during which tumors generate immune tolerance. An inhibitory effect of fungal bioactive complexes on some molecular mediators of proliferative signaling and components of proinflammatory (synergistic with cancer) immunity can be considered less significant. The effect of fungal bioactive complexes on vital (including overexpressed) targets of cancer cells is even more limited. The results of this study stress that mycotherapy is only one of the tools that can be used to balance remission. Palliative mycotherapy is associated with polyphenols composites, which contribute to detoxification and to the suppression of inflammation and pain sensation.

The Brown Roll-Rim Mushroom, Paxillus involutus (Agaricomycetes), as a Promising Biomedical Research Resource.

The brown roll-rim mushroom (Paxillus involutus) quickly produces biomass in nature, although, being a mycorrhizal fungus, it is rather poorly maintained in culture. Information about its toxic properties is controversial. Until the mid-20th century, the species was considered as an edible fungus; however, data later accumulated regarding its poisonous properties, leading to the term "Paxillus syndromeP. involutus. Since mushrooms can have quite a few unidentified antigens complementary to B-lymphocyte receptors, this is a hidden danger of using unfractionated mushroom raw materials for preventive and oncotherapy purposes, and we hope that this article stimulates immunological groups worldwide to identify the "X" antigen related to the Paxillus syndrome. Oncotherapy effects of the known bioactive complexes of P. involutus are associated with a specific inhibition of some growth receptors of the cancer cell, whereas experimentation with purified substances of P. involutus and various families of growth receptors of cancer cell has good prospects. A clear speciation is fixing within the P. involutus complex. The key for identification of species of P. involutus complex is given and cultural characteristics of P. involutus strains kept at Komarov Botanical Institute Basidiomycetes Culture Collection are presented.

Profiles of Little-Known Medicinal Polypores: Funalia trogii (Agaricomycetes).

The purpose of this study was to comprehensively characterize little-known polypores that have recently been found to possess anticancer activity and thus can be used in targeted cancer therapy. Funalia trogii is a polypore with bipolar distribution and has been found by harvesters working in taiga forests, broadleaf forests, and forest-steppes of the Holarctic, and in semiarid temperate forests of the Southern Hemisphere. Substances such as gibberellic acid, abscisic acid, indole-3-acetic acid, and natural cytokinin were determined in culture media of F. trogii. Also, laccases and peroxidases of spare action have been reported in F. trogii culture media. All of the aforementioned substances can be used in targeted cancer therapy, but further investigation of F. trogii is recommended; more details of its health benefits could expand its use in mycotherapy.

Current and Future Research Trends in Agricultural and Biomedical Applications of Medicinal Mushrooms and Mushroom Products (Review).

Here, we analyze the status and future trends in the study of medicinal mushrooms (MMs) in agriculture and biomedicine. Fruiting bodies of mushrooms are heterotrophic organisms that obtain all their nutritive requirements from the substrate. Mushroom substrates are agro-industrial plant residues and forest byproducts, which are usually called lignocellulosic materials. A good substrate for mushroom growth must be suitable both chemically and physically, as well as have the proper conditions for microbial activities. Under suitable conditions, mushrooms can excrete key enzymes for unlocking indigestible lignocellulosic biomasses to help provide sources of nourishment. The production of enzymes by mushroom mycelia plays a crucial part in the colonization process and is an important determinant of mushroom yields. The sense of purpose and vision for mushroom industries is also briefly discussed. Special attention is given to the use of mushroom extracts with antiphytopathologenic and insecticidal properties in modern agriculture. In the second part of this article, we summarize biomedical applications of medicinal mushrooms, which are currently used as 1) dietary food, 2) dietary supplement products, 3) a new class of drugs called "mushroom pharmaceuticals or mushroom drugs", 4) natural biocontrol agents in plant protection demonstrating insecticidal, fungicidal, bactericidal, herbicidal, nematocidal, and antiphytoviral activities, and 5) cosmeceuticals. We also aimed to draw attention to many critically important unsolved problems in the future development of medicinal mushroom science in the 21st century, including problems of production, standardization, and safety of mushroom dietary supplement products, as well as to discuss the problems of developing new medicinal mushroom drugs based not only on beta-glucans polysaccharides but also on low-molecular-weight secondary metabolites.

Enzymatic System of Antioxidant Protection of Erythrocytes in Diabetic Rats Treated with Medicinal Mushrooms Agaricus brasiliensis and Ganoderma lucidum (Agaricomycetes).

Excessive glucose concentrations in blood and cells promote the intensification of auto-oxidation. This is one of the mechanisms through which free radicals form in hyperglycemia. As a result of hyperglycemia, oxidative stress develops and lipid peroxidation (LPO) is enhanced. Erythrocytes are particularly susceptible to reactive oxygen species and LPO, which can violate cell functions. This article describes the analysis of the influence of mycelia from the medicinal mushrooms Agaricus brasiliensis and Ganoderma lucidum on the enzymatic link of the antioxidant system in rat erythrocytes under streptozotocin-induced diabetes mellitus. Oxidative stress was strengthened in red blood cells of diabetic rats, as evidenced by decreased activity of antioxidant enzymes such as superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase, and by increased amounts of thiobarbituric acid-positive products, which are markers of LPO. Administration of A. brasiliensis and G. lucidum submerged cultivated mycelial powder to animals with streptozotocin-induced diabetes restored superoxide dismutase, catalase, and glutathione peroxidase activity and reduced the amounts of thiobarbituric acid-positive products to control values, but did not affect the activity of glutathione reductase.

What Is Ganoderma lucidum in the Molecular Era?

The scientific name Ganoderma lucidum has long been used in the global medicinal mushroom market, and many publications have proven its pharmacological properties and chemical components. Although several Ganoderma species have been described worldwide as having morphology considerably similar to that of G. lucidum s. str., this binomial is still the most frequently used in pharmacological studies. However, the use of particularly divergent nomenclature has caused major difficulties in the evaluation of the results of pharmacological studies. This article is intended to provide a nomenclatural and taxonomic overview of the medically important G. lucidum group, that is, G. lucidum aggregate and G. lingzhi. Moreover, we evaluate the possibilities of how nomenclatural changes can help to avoid misunderstandings in thousands of publications and highlight scientifically correct interpretations for future studies.

Medicinal Mushrooms in Human Clinical Studies. Part I. Anticancer, Oncoimmunological, and Immunomodulatory Activities: A Review.

More than 130 medicinal functions are thought to be produced by medicinal mushrooms (MMs) and fungi, including antitumor, immunomodulating, antioxidant, radical scavenging, cardiovascular, antihypercholesterolemic, antiviral, antibacterial, antiparasitic, antifungal, detoxification, hepatoprotective, antidiabetic, and other effects. Many, if not all, higher Basidiomycetes mushrooms contain biologically active compounds in fruit bodies, cultured mycelia, and cultured broth. Special attention has been paid to mushroom polysaccharides. Numerous bioactive polysaccharides or polysaccharide-protein complexes from MMs seem to enhance innate and cell-mediated immune responses, and they exhibit antitumor activities in animals and humans. While the mechanism of their antitumor actions is still not completely understood, stimulation and modulation of key host immune responses by these mushroom compounds seems to be central. Most important for modern medicine are polysaccharides and low-molecular weight secondary metabolites with antitumor and immunostimulating properties. More than 600 studies have been conducted worldwide, and numerous human clinical trials on MMs have been published. Several of the mushroom compounds have proceeded through phase I, II, and III clinical studies and are used extensively and successfully in Asia to treat various cancers and other diseases. The aim of this review is to provide an overview of and analyze the literature on clinical trials using MMs with human anticancer, oncoimmunological, and immunomodulatory activities. High-quality, long-term, randomized, double-blind, placebo-controlled clinical studies of MMs, including well-sized population studies are definitely needed in order to yield statistical power showing their efficacy and safety. Clinical trials must obtain sufficient data on the efficacy and safety of MM-derived drugs and preparations. Discussion of results based on clinical studies of the anticancer, oncoimmunological, and immunomodulating activity of MMs are highlighted. Epidemiological studies with MMs are also discussed.

Typification and Characterization of Trametes multicolor (Agaricomycetes), a Perspective Species of Medicinal Mushrooms.

Nomenclature revision and enlarged taxonomical descriptions are still needed for some well-known species whose interpretation is complicated by many nomenclature or taxonomical problems. The polyporoid fungus widely known as Trametes ochracea (= Coriolus zonatus) belongs to such a problematic group. At the same time, recent data show that this species, like its sister species T. versicolor, seems to be a perspective subject for fungal biotechnology and pharmacology. This article is devoted to stabilizing the nomenclature of the species in question via lectotypification and epitypification of Boletus multicolor. It will clarify the name T. multicolor as applied to this species is nomenclaturally correct and useful, free of further problems. An expanded species description and cultural characterization of epitype materials are presented.

Profiles of Little-Known Medicinal Polypores: Earliella scabrosa (Agaricomycetes).

The purpose of this study was to comprehensively characterize a little-known polypore that has recently been found to possess anticancer activity and thus can also be used in targeted cancer therapy. Earliella scabrosa is a polypore with pantropical distribution and can be found in rainforests in both the Eastern and Western Hemispheres. Some reports have described its antioxidant properties and free radical scavenging ability. Moreover, isocoumarin, which has been successfully used in targeted cancer therapy, was found in extracts of this fungus. We recommend further research of E. scabrosa so that more details of its health benefits could be used in mycotherapy.

Anti-Inflammation Properties of Fruiting Bodies and Submerged Cultured Mycelia of Culinary-Medicinal Higher Basidiomycetes Mushrooms.

This research shows the phenolic composition and anti-inflammation properties of fruiting bodies and mycelia of 15 strains of 12 species of higher Basidiomycetes medicinal mushrooms. In this research, 15 extracts were prepared and their effects on inflammation-related mediators in RAW 264.7 cells were evaluated. In the extracts, amounts of total phenols ranged from 8.47 to 70.32 gallic acid equivalents mg/g and amounts of flavonoids ranged from 0.13 to 15.21 rutin equivalents mg/g. The production of nitric oxide, tumor necrosis factor-α, and interleukin-6 was decreased at different levels by these extracts, whereas the production of interleukin-10 was increased by 6 of the extracts. Overall, Cordyceps militaris fruiting bodies, Grifola frondosa fruiting bodies, and Ophiocordyceps sinensis mycelia might be used to ameliorate inflammatory responses.