Medicinal Mushrooms: Bioactive Compounds, Use, and Clinical Trials.

Medicinal mushrooms have important health benefits and exhibit a broad spectrum of pharmacological activities, including antiallergic, antibacterial, antifungal, anti-inflammatory, antioxidative, antiviral, cytotoxic, immunomodulating, antidepressive, antihyperlipidemic, antidiabetic, digestive, hepatoprotective, neuroprotective, nephroprotective, osteoprotective, and hypotensive activities. The growing interest in mycotherapy requires a strong commitment from the scientific community to expand clinical trials and to propose supplements of safe origin and genetic purity. Bioactive compounds of selected medicinal mushrooms and their effects and mechanisms in in vitro and in vivo clinical studies are reported in this review. Besides, we analyzed the therapeutic use and pharmacological activities of mushrooms.

Molecular evidence supports simultaneous association of the achlorophyllous orchid Chamaegastrodia inverta with ectomycorrhizal Ceratobasidiaceae and Russulaceae.

BACKGROUND: Achlorophyllous orchids are mycoheterotrophic plants, which lack photosynthetic ability and associate with fungi to acquire carbon from different environmental sources. In tropical latitudes, achlorophyllous forest orchids show a preference to establish mycorrhizal relationships with saprotrophic fungi. However, a few of them have been recently found to associate with ectomycorrhizal fungi and there is still much to be learned about the identity of fungi associated with tropical orchids. The present study focused on mycorrhizal diversity in the achlorophyllous orchid C. inverta, an endangered species, which is endemic to southern China. The aim of this work was to identify the main mycorrhizal partners of C. inverta in different plant life stages, by means of morphological and molecular methods. RESULTS: Microscopy showed that the roots of analysed C. inverta samples were extensively colonized by fungal hyphae forming pelotons in root cortical cells. Fungal ITS regions were amplified by polymerase chain reaction, from DNA extracted from fungal mycelia isolated from orchid root samples, as well as from total root DNA. Molecular sequencing and phylogenetic analyses showed that the investigated orchid primarily associated with ectomycorrhizal fungi belonging to a narrow clade within the family Ceratobasidiaceae, which was previously detected in a few fully mycoheterotrophic orchids and was also found to show ectomycorrhizal capability on trees and shrubs. Russulaceae fungal symbionts, showing high similarity with members of the ectomycorrhizal genus Russula, were also identified from the roots of C. inverta, at young seedling stage. Ascomycetous fungi including Chaetomium, Diaporthe, Leptodontidium, and Phomopsis genera, and zygomycetes in the genus Mortierella were obtained from orchid root isolated strains with unclear functional role. CONCLUSIONS: This study represents the first assessment of root fungal diversity in the rare, cryptic and narrowly distributed Chinese orchid C. inverta. Our results provide new insights on the spectrum of orchid-fungus symbiosis suggesting an unprecedented mixed association between the studied achlorophyllous forest orchid and ectomycorrhizal fungi belonging to Ceratobasidiaceae and Russulaceae. Ceratobasidioid fungi as dominant associates in the roots of C. inverta represent a new record of the rare association between the identified fungal group and fully mycoheterotrophic orchids in nature.

Tamarix arborea var. arborea and Tamarix parviflora: Two species valued for their adaptability to stress conditions.

The choice of stress resistant and highly adaptable species is a fundamental step for landscaping and ornamental purposes in arid and coastal environments such as those in the Mediterranean basin. The genus Tamarix L. includes about 90 species with a high endurance of adversity. We investigated the water relations and photosynthetic response of Tamarix arborea (Sieb. ex Ehrenb.) Bge. var. arborea and T. parviflora DC. growing in an urban environment. Both species showed no evidence of drought or salt stress in summer, and appeared to follow two strategies with T. arborea var. arborea investing in high carbon gain at the beginning of the summer, and then reducing photosynthetic activity at the end of the season, and T. parviflora showing lower but constant levels of photosynthetic activity throughout the vegetative season. For landscaping and ornamental purposes, we suggest T. arborea var. arborea when a fast-growing, high-cover species is necessary, and T. parviflora when less-invasive species are required.

The mineral contents of some Boletaceae species from Sicily (Southern Italy).

Data on the accumulation of metals in wild edible and inedible macrofungi of the Boletaceae family are discussed here and compared with data reported in literature from northern Italy and other European countries, as well as from China, Brazil, and Africa. The results show a significant difference in the values detected in Sicilian fungi compared to those reported in the literature.

Checklist of Ornamental Trees, Shrubs, and Succulents of Apulia (Southern Italy).

In this study we focused on the need to fill a knowledge gap among Italian botanical studies namely that of ornamental species census. In particular, we addressed one of the regions in southern Italy with less knowledge in the field of such studies and with an obvious presence of non-native species. A widespread census of the Apulian territory was carried out between 2021 and 2024 in both urban and suburban areas including street trees, parks, and private and historic gardens. The inventory of ornamental trees, shrubs, and succulents of Apulia (southern Italy) was carried out in six provinces, i.e., Bari, Barletta-Andria-Trani, Brindisi, Foggia, Lecce, and Taranto. The checklist comprises 287 taxa (including 265 species, 6 varieties, 5 subspecies, and 11 forms) included in 179 genera belonging to 78 families. We evaluated the number of taxa per families and genera, the presence of each taxa in the provinces of Apulia, the number of taxa per occurrence status, growth forms, geographical origin, and the number of native and alien taxa and also the artificial hybrids. Remarks of the most significant taxa and evaluation of geographical distribution in Italy were also taken into consideration. A large number of surveyed taxa (51.74%) are comprised in the list reported in the recent study on allochthonous vascular flora in Italy with a marked prevalence of Neophyte Casual Alien and Neophyte Naturalized Alien species.

Mushroom-Based Supplements in Italy: Let's Open Pandora's Box.

Mushrooms and derivates are well known to the scientific community for having different health benefits and exhibit a wide range of pharmacological activities, including lipid-lowering, antihypertensive, antidiabetic, antimicrobic, antiallergic, anti-inflammatory, anticancer, immunomodulating, neuroprotective and osteoprotective actions. In Europe, medical mushrooms are mainly marketed in the form of food supplements as single components or combined with other nutraceuticals. In this context, the first peculiarity that distinguishes it is the safety established through the "history of consumption" that characterizes that mushroom. However, the cultivation of medicinal mushrooms on a large scale is performed mainly in China, where most of the production facilities do not have internationally recognized good manufacturing practices, despite that many European companies that sell myotherapies are supplied by Chinese manufacturers. This is particularly evident in Italy, where an arsenal of mushroom products is marketed in the form of powders and extracts not always of ascertained origin and sometimes of doubtful taxonomic identification, and thus not meeting the quality criteria required. The growing interest in mycotherapy involves a strong commitment from the scientific community to propose supplements of safe origin and genetic purity as well as to promote clinical trials to evaluate its real effects on humans. The purpose of this research is to analyze different mushroom-based dietary supplements used in medicine as monotherapy on the Italian market and to evaluate their composition and quality. The molecular identification of the sequences with those deposited in GenBank allowed for identifying 6 out of 19 samples, matching with those deposited belonging to the species indicated in the label, i.e., Lentinula edodes (samples 1, 4, 12 and 18) and Ganoderma lucidum (samples 5 and 10). Samples containing Ganoderma, labeled in the commercial product as G. lucidum, showed sequences that showed homology of 100% and 99% with G. resinaceum and G. sichuanense. An additional investigation was carried out in order to determine the active fungal ingredients, such as ergosterol, aflatoxins, heavy metals, nicotine and total glucan. The results obtained and shown in the manuscript highlight how the data were not only in line with what is expected with respect to what is indicated in the labels.

Antifungal Activity of Medicinal Mushrooms and Optimization of Submerged Culture Conditions for Schizophyllum commune (Agaricomycetes).

The main goal of the present study was the exploration of the antifungal properties of Agaricomycetes mushrooms. Among twenty-three tested mushrooms against A. niger, B. cinerea, F. oxysporum, and G. bidwellii, Schizophyllum commune demonstrated highest inhibition rates and showed 35.7%, 6.5%, 50.4%, and 66.0% of growth inhibition, respectively. To reveal culture conditions enhancing the antifungal potential of Sch. commune, several carbon (lignocellulosic substrates among them) and nitrogen sources and their optimal concentrations were investigated. Presence of 6% mandarin juice production waste (MJPW) and 6% of peptone in nutrient medium promoted antifungal activity of selected mushroom. It was determined that, extracts obtained in the presence of MJPW effectively inhibited the grow of pathogenic fungi. Moreover, the content of phenolic compounds in the extracts obtained from Sch. commune grown on MJPW was several times higher (0.87 ± 0.05 GAE/g to 2.38 ± 0.08 GAE/g) than the extracts obtained from the mushroom grown on the synthetic (glycerol contained) nutrient medium (0.21 ± 0.03 GAE/g to 0.88 ± 0.05 GAE/g). Flavonoid contents in the extracts from Sch. commune varied from 0.58 ± 0.03 to 27.2 ± 0.8 mg QE/g. Identification of phenolic compounds composition in water and ethanol extracts were provided by mass spectrometry analysis. Extracts demonstrate considerable free radical scavenging activities and the IC50 values were generally low for the extracts, ranging from 1.9 mg/ml to 6.7 mg/ml. All the samples displayed a positive correlation between their concentration (0.05-15.0 mg/ml) and DPPH radical scavenging activity. This investigation revealed that Sch. commune mushroom has great potential to be used as a source of antifungal and antioxidant substances.

Two rare northern Entoloma species observed in Sicily under exceptionally cold weather conditions.

The biology and ecology of many Entoloma species is still poorly known as well as their geographical distribution. In Italy, there are no studies on the influence of weather on fungal abundance and richness and our knowledge on the ecology and distribution of Entoloma species needs to be improved. The discovery of two Entoloma species in Sicily (southern Italy), reported in the literature as belonging to the habitat of north European countries, was the basis leading to the assumption that anomalous climatic conditions could stimulate the growth of northern entolomas in the southernmost Mediterranean regions. The results of this study show that the presence of northern Entoloma species in Sicily is not influenced by the Mediterranean type of vegetation, by edaphic or altitudinal factors but by anomalous climatic trends of precipitations and temperatures which stimulate the fructification of basidiomata in correspondence with a thermal shock during autumn.

The nutritional composition of selected wild edible mushrooms from Sicily (southern Italy).

The wide consumption of wild fungi by the local population is the basis for an evaluation of the as yet unknown nutritional composition of some selected species. Wild edible mushrooms (Fistulina hepatica, Infundibulicybe geotropa, Laetiporus sulphureus, Macrolepiota procera var. procera and Suillus granulatus) were collected in a number of Sicilian (southern Italian) forest ecosystems and analysed according to standard methodologies of fungal analysis, for their basic composition (ash, water, protein, fat, carbohydrate and vitamin). The results showed that the investigated mushrooms could be suggested as a source of nutritional elements for the human diet.

The Checklist of Sicilian Macrofungi: Second Edition.

Approximately 30 years after the publication of the first Sicilian checklist of macrofungi, a new updated version is presented here. The census of macromycetes was carried out through periodic observations in different agricultural and forest ecosystems, in urban areas, in public and private gardens, and in botanical gardens. The 1919 infraspecific taxa included in 508 genera belonging to 152 families were collected in the Sicilian territory. Ectomycorrhizal fungi are the most represented ecological category, followed by saprotrophs on wood, saprotrophs on litter, and terricolous saprotrophs. The interest in this rich group of organisms is evidenced by the nutritional and therapeutic value of a high percentage of species. The actions linked to the National Recovery and Resilience Plan and The Network for the Study of Mycological Diversity will further increase the number of macrofungi for Sicily in the future.

Untargeted Metabolomics Used to Describe the Chemical Composition, Antioxidant and Antimicrobial Effects of Extracts from Pleurotus spp. Mycelium Grown in Different Culture Media.

Pleurotus species isolated in vitro were studied to determine the effect of different media on their production of secondary metabolites, antimicrobial, and antioxidant activity. The different metabolites among Pleurotus samples covered a total of 58 pathways. Comparisons were made between the metabolic profiles of Pleurotus spp. mycelia grown in two substrates: Potato-dextrose-agar-PDA, used as control (S1), and PDA enriched with 0.5 % of wheat straw (S2). The main finding was that the metabolic pathways are strongly influenced by the chemical composition of the growth substrate. The antibacterial effects were particularly evident against Escherichia coli, whereas Arthroderma curreyi (CCF 5207) and Trichophyton rubrum (CCF 4933) were the dermatophytes more sensitive to the mushroom extracts. The present study supports more in-depth investigations, aimed at evaluating the influence of growth substrate on Pleurotus spp. antimicrobial and antioxidant properties.

The Role of Medicinal Mushrooms in Brain Cancer Therapies: Review.

Medicinal mushrooms are considered an unlimited source of polysaccharides (mainly ß-glucans) and polysaccharide-protein complexes and possess various immunological and anticancer properties. In addition, their use in integrative medicine leads to a clear reduction of side effects in patients undergoing chemotherapy or radiotherapy. The literature reports a number of beneficial effects of using mushrooms as health supplements in patients affected by high-grade glioma. The effects of medicinal mushrooms on side effects in patients with brain cancer and a case study report are also described in this review.

Comparison of Two Schizophyllum commune Strains in Production of Acetylcholinesterase Inhibitors and Antioxidants from Submerged Cultivation.

In recent years, fungi have been recognized as producers of acetylcholinesterase (AChE) inhibitors, agents important for the prevention of Alzheimer's disease (AD). This study aimed to examine the AChE inhibitory, the antioxidative and antibacterial activity of two different Schizophyllum commune strains that originated from Serbia (SRB) and Italy (IT). Submerged cultivation of grown mycelia (M) and fermentation broth (F) of ethanol (EtOH) and polysaccharide (PSH) extracts lasted for 7, 14, 21 and 28 days. For AChE activity Ellman method was performed, while for antioxidative activity, sevendifferent assays were conducted: DPPH, ABTS, FRAP, SOA, OH, NO together with total phenolic content. Antimicrobial screen, LC-MS/MS technique and FTIR measurements were performed. Different isolates exhibited different AChE activity, with PSH being the strongest (SRB, M, 28 days IC90 79.73 ± 26.34 µg/mL), while in EtOH extracts, IT stood out (F, 14 days, IC50 0.8 ± 0.6 µg/mL). PSH extracts (7 days) exhibit significant antioxidative activity (AO), opposite to EtOH extracts where 14 and 21days periods stood out. Only tw extracts showed antibacterial activity. Following LC-MS/MS analysis p-hydroxybenzoic and gallic acids were the most abundant phenolics. PSH extracts demonstrated remarkable results, making this study debut and introducing S. commune as a valuable resource of AChE inhibitors.

JNK pathway and heat shock response mediate the survival of C26 colon carcinoma bearing mice fed with the mushroom Pleurotus eryngii var. eryngii without affecting tumor growth or cachexia.

In the last few years, there has been emerging interest in developing treatments against human diseases using natural bioactive content. Here, the powder of the edible mushroom Pleurotus eryngii var. eryngii was mixed with the normal diet of mice bearing C26 colon carcinoma. Interestingly, it was evidenced by a significant increase in the survival rate of C26 tumor-bearing mice accompanied by a significant increase in Hsp90 and Hsp27 protein levels in the tumors. These data were paralleled by a decrease in Hsp60 levels. The mushroom introduced in the diet induced the inhibition of the transcription of the pro-inflammatory cytokines IL-6 and IL-1 exerting an anti-inflammatory action. The effects of the mushroom were mediated by the activation of c-Jun NH2-terminal kinases as a result of metabolic stress induced by the micronutrients introduced in the diet. In the tumors of C26 bearing mice fed with Pleurotus eryngii there was also a decreased expression of the mitotic regulator survivin and the anti-apoptotic factor Bcl-xL as well as an increase in the expression levels of Atg7, a protein that drives autophagy. In our hypothesis the interplay of these molecules favored the survival of the mice fed with the mushroom. These data are promising for the introduction of Pleurotus eryngii as a dietary supplement or as an adjuvant in anti-cancer therapy.

Potential Activity of Albino Grifola frondosa Mushroom Extract against Biofilm of Meticillin-Resistant Staphylococcus aureus.

Mushroom extracts are a rich source of natural compounds with antimicrobial properties, which are able to prevent, to some extent, the growth of foodborne pathogens. The aim of this study was to investigate the potential of extracts from albino Grifola frondosa (GF), commonly known as maitake, to inhibit the growth of some bacteria and the biofilm production by Staphylococcus aureus. We obtained not only a significant reduction of OD score between biofilm and biofilm plus albino G. frondosa extract group, but also a reduction of category of biofilm. In addition, we observed a significant presence of isolates with strong category for the biofilm group and a significant presence of isolates with absent category for the biofilm plus albino G. frondosa extract group. These results confirm that the use of albino G. frondosa extract reduces in significant way the presence of biofilm. Our results suggest and confirm that albino G. frondosa extracts could be employed as functional food and could be used as a natural additive for food process control and food safety.

Polysaccharides from Pleurotus eryngii var. elaeoselini (Agaricomycetes), a New Potential Culinary-Medicinal Oyster Mushroom from Italy.

Three water-soluble glucans (PELPS-A1, PELPS-A2, and PELPS-A3) purified from the hot water extract of the basidiomata of an edible mushroom Pleurotus eryngii var. elaeoselini by chromatography on DEAE-cellulose 32 and Sephadex G-100 column were found to consist of only D-glucose as monosaccharide constituent. Structural investigation was carried out by acid hydrolysis, periodate oxidation, and NMR experiments (1H-NMR, 13C-NMR, DQF-COSY, TOCSY, ROESY, HMQC, and HMBC). On the basis of these experiments, the structures of the repeating unit of the three isolated polysaccharides were established as follows: (1) PELPS-A1: {[→3)-α-D-Glcp-(1→]3→4)-α-D-Glcp-(1→2)-α-D-Glcp-(1→6)-α-D-Glcp-(1[→6)-ß-D-Glcp-(1→]2}n 6 ↑ 1 α-D-Glcp (2) PELPS-A2: [→6)-ß-D-Glcp-(1→6)-ß-D-Glcp-(1→6)-ß-D-Glcp-(1→]n 3 ↑ 1 ß-D-Glcp (3) PELPS-A3: [→6)-α-D-Glcp-(1→6)-α-D-Glcp-(1→6)-α-D-Glcp-(1→]n The dried basidiomata of P. eryngii var. elaoselini were tested for their antioxidant activity by DPPH and hydroxyl radical scavenging assays. The crude extract has shown a SC50 of 1.4 mg/mL for DPPH test while a SC50 of 5.7 mg/mL was observed for hydroxyl radical scavenging activity test. The antioxidant activity of PELPS-A1, PELPS-A2, and PELPS-A3, evaluated as hydroxyl radical scavenging activity, was similar and significant, suggesting their use as antioxidants.

Medicinal Mushrooms as Part of the "Third Mission" Activities of Univesities - A Science to Business Initiative Related to Mycotherapy.

In Italy, the National Agency for the Evaluation of the University System and Research (ANVUR) carries out a systematic evaluation of the "Third Mission" activities of universities and research bodies. In this perspective, universities already engaged in research on medicinal mushrooms and on their potential applications in the industrial sector set the frame for collaboration with large, well-reputed private companies. In Italy, one of the major problems of mycotherapy is related to lack of certification and the dubious origin/identity of mushroom extracts used by the industry. Hence, products deriving from medicinal mushrooms that are in trade do not often meet the required quality criteria. In this paper, a multipartner collaboration is presented, which aims at the bottom to top development of nutraceutical products from Pleurotus mushrooms in agreement to science-to-business (S2B) marketing.

The Potential Role of Medicinal Mushrooms in the Prevention and Treatment of Gynecological Cancers: A Review.

A review of scientific information about the potential role of medicinal mushrooms in the prevention and treatment of gynecological cancers, human immunodeficiency virus, and human papillomavirus infections is reported here. The results of in vivo and in vitro experiments on 16 different species of Basidiomycetes and three Ascomycetes, which possess chemopreventive potential and are effective in clinical application in combination with chemotherapy, are also discussed. Medicinal mushroom extracts confirm an evident efficacy on the reduction of tumor cell proliferation and side effects in patients with gynecological tumors who are undergoing chemotherapy treatments. This review, the first on the use of medicinal mushrooms in the prevention and treatment of gynecological cancers, aims to highlight the remarkable potential of mushrooms in integrated oncology.

Pleurotus opuntiae revisited - An insight to the phylogeny of dimitic Pleurotus species with emphasis on the P. djamor complex.

The name Pleurotus opuntiae is indiscriminately used for describing mushrooms with white to off-white to white-grey pilei with short or absent stipe and dimitic hyphal system, which grow on plants of the genera Opuntia, Yucca, Agave, Phytolacca etc. However, the outcome of the present study evidences that this name should be reserved for specimens deriving from the Mediterranean area only; an epitype originating from Italy on Opuntia ficus-indica is designated. Pertinent material was sequenced by using the internal transcribed spacer region (ITS) and found to be phylogenetically related to P. djamor from Kenya and Nigeria, while members of the P. djamor complex from other continents were clearly more distant. Results were further corroborated by examining the large subunit of nuclear ribosomal DNA (LSU) and the second subunit of RNA polymerase II (RPB2). The P. djamor complex shows high intraspecific polymorphism evidenced by sequence divergence and genetic distance values, presents a cosmopolitan distribution and also comprises material initially identified as P. flabellatus, P. opuntiae, P. ostreatoroseus, P. parsonsiae and P. salmoneostramineus. An ITS tree including representative specimens from all major Pleurotus species is provided for the first time and ambiguous taxa are discussed in the context of new findings.

Effects of Diets Supplemented with Medicinal Mushroom Myceliated Grains on Some Production, Health, and Oxidation Traits of Dairy Ewes.

The beneficial properties of mushrooms' bioactive compounds indicate their potential for use as performance-enhancing natural additives for livestock animals. A study was undertaken to evaluate the effects of diets supplemented with mushroom myceliated grains (MMGs) fed to dairy ewes on intestinal parasite load, milk production, milk fatty acid (FA) composition, and cheese oxidative stability. During an 8-week experimental period, 21 lactating Valle del Belice ewes were divided into 3 groups named MMG20, MMG10, and MMG0. Ewes in each group were fed hay ad libitum and 1.3 kg/day/head of 1 of 3 concentrates with MMGs at 20% (MMG20), 10% (MMG10), or 0% (MMG0). The ewes fed MMG20 had comparable dry matter (DM) and nutrients intake, fewer intestinal parasite infections, a tendency toward higher milk yield, and higher milk casein content (4.78% in MMG20 vs. 4.32% in MMG10 and 4.27% in MMG0; P < 0.05), and they produced cheese with less intense yellow color and a lower secondary lipid oxidation, than the ewes in the MMG10 and MMG0 groups. A higher antioxidant capacity was observed (17.83 mmol Trolox equivalent/kg DM in the MMG20 group vs. 9.97 and 9.18 mmol Trolox equivalent/kg DM in the MMG10 and MMG0 groups, respectively; P < 0.001), suggesting a higher oxidative stability of cheese fat and a probable enrichment of cheese with antioxidant compounds inherent in or induced by MMGs. The inclusion of MMGs in the diet did not affect the amounts of health-promoting polyunsaturated FAs in milk, with the exception of n-3 eicosapentaenoic acid, which was found only in milk from the MMG-treated ewes. These promising results merit further investigation into the potential use of medicinal mushrooms to enhance animal health and production.