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SCIENCE & INGREDIENTS:
Agaricus bisporus
Nature has been a source of Medicinal agents for thousands of years and an impressive number of modern drugs have been isolated from natural sources, based on their use in traditional medicine. Since ancient time’s plants as well as fungus sources of Medicinal compounds have continued to play a dominant role in maintenance of human health. Over 50% of all modern clinical drugs are of natural product origin and play an important role in drug development programs in the pharmaceutical industry. Mushrooms are an important natural source of food and medicine. Traditional aboriginals knew the importance of edible and wild Mushrooms, and these are now being screened for their bioactivity in various ailments.
THE nutritional AND medical benefits OF AGARICUS BISPORUS : A REVIEW
Mushrooms are considered as potential source of many essential nutrients and therapeutic bioactive compounds. Agaricus bisporus belongs to Basidiomycetes family and the most important commercially cultivated Mushroom in the world. The rich nutrients like carbohydrates, proteins, lipids, fibers, minerals, and vitamins present this Mushroom as famous healthy food. Moreover, because of the presence of some active ingredients, such as polysaccharides, lipopolysaccharides, essential amino acids, peptides, glycoproteins, nucleosides, triterpenoids, lectins, fatty acids and their derivatives, these Mushrooms have been reported to have antimicrobial, anticancer, antidiabetic, antihypercholesterolemic, antihypertensive, hepatoprotective and antioxidant activities.
antioxidant and anti-aging effects of acidic-extractable polysaccharides by Agaricus bisporus
This study was designed to investigate the antioxidant and anti-aging effects of D-galatose-induced (D-gal-induced) aging mice as well as monosaccharide compositions of acidic-extractable polysaccharides (AcAPS) and its major purified fractions (AcAPS-1, AcAPS-2 and AcAPS-3) from the fruiting body of Agaricus bisporus. The Results suggested that both AcAPS and its purified fractions might be suitable for functional foods and natural drugs in preventing the acute aging–associated diseases.
In present study, the soluble polysaccharides by enzyme-assisted extraction from Agaricus bisporus (EnAPS) and its purified fractions of EnAPS-1, -2 and -3 were successfully obtained, and the antioxidant activities and anti-aging effects were investigated. The in vitro antioxidant assay demonstrated that EnAPS-2 had superior scavenging activities on DPPH and hydroxyl radicals, chelating activities of Fe2+ and reducing power. The in vivo animal experiments showed that both EnAPS and its purifies fractions had potential anti-aging effects against the d-galctose-induced aging diseases on liver, kidney, brain and skin, possibly by increasing the antioxidant enzymes, reducing the lipid peroxidation, improving the organ functions and remitting the lipid metabolism. The Conclusions demonstrated that the polysaccharides by A. bisporus might be suitable for applying functional foods and natural drugs in preventing and delaying the aging and its complications.
Composition and biological properties of agaricus bisporus fruiting bodies– a review
White Agaricus bisporus is both the most popular and the most commonly eaten edible Mushroom species in the world. It is popular not only because of its taste, but also due to its high level of nutrients: dietary fiber (chitin), essential, semi-essential amino acids, unsaturated fatty acids including linoleic and linolenic acids, easily digestible proteins, sterols, phenolic and indole compounds, and vitamins − especially provitamin D2 andB1 , B2 , B6 , B7 , and C. fruiting bodies of A. bisporus have antioxidant, antibacterial, anti-inflammatory, antitumor, and immunomodulatory activity.
anti-Aromatase activity of phytochemicals in White Button mushrooms (Agaricus bisporus)
The studies showed that Mushroom extract decreased both tumor cell proliferation and tumor weight with no effect on rate of apoptosis. Therefore, our studies illustrate the anticancer activity in vitro and in vivo of Mushroom extract and its major fatty acid constituents.
Results demonstrated that the polysaccharides, especially AlAPS-2, showed potential antiaging and hepatoprotective effects by enhancing the antioxidant status, decreasing serum hepatic enzyme activities, and improving the lipid metabolism. This study suggested that the polysaccharides extracted and purified from A. bisporus could be exploited as a potent dietary supplement to attenuate aging and prevent age-related diseases.
Fungi are vital to numerous industrial and household processes, especially producing cheeses, beer, wine, and bread, and they are accountable for breaking down organic matter. The remarkable Medicinal and nutritional values of the Mushrooms have increased their consumption. Agaricus bisporus belongs to the Agaricaceae family, and it is a top-ranked cultivated Mushroom that is well known for its edibility. A. bisporus is rich in nutrients such as carbohydrates, amino acids, fats, and minerals and has potential anticancer, antioxidant, anti-obesity, and anti-inflammation properties. The bioactive compounds extracted from this Mushroom can be used for the treatment of several common human diseases including cancer, bacterial and fungal infections, diabetes, heart disorder, and skin problems.
phytochemical and pharmacological potentials of Agaricus bisporus
Agaricus bisporus showed significant anti-inflammatory, analgesic, antipyretic, antioxidant activities and antimicrobial activity.
anti-tumor activity of Agaricus bisporus Extracts and its Relation with IL-2 in tumor-Bearing Mice
Mushroom is widely used as a traditional Medicinal fungus, and it has been known to exhibit immune–stimulatory and anti-cancer activity. The Results showed that both extracts significantly inhibit the growth of tumor up to 72.2% at the end of experiment, while only the ethanolic extract significantly increased the level of IL-2 production from 11.2 and 16.9 pg/ml up to 26.4 and 42.5 pg/ml after 2 and 4 weeks of treatment respectively.
Study on preliminary phytochemical screening
and anti ulcer activity of Agaricus bisporus
Peptic ulcer is the most prevalent gastrointestinal disease. Even though a wide range of drugs are available for the treatment of peptic ulcer, but many of these do not fulfill all the requirements and have side effects. The Results of the present study reveal that the A. bisporus having efficiency in the gastro protective activity. It is recommended that the above Mushroom can be further studied for their anti ulcer efficacy in human subjects.
Agaricus bisporus (white button Mushroom; WBM) contains high levels of dietary fibers and antioxidants including vitamin C, D, and B12; folates; and polyphenols that may provide beneficial effects on cardiovascular and diabetic diseases. It was Concluded that A bisporus Mushroom had both hypoglycemic and hypolipidemic activity in rats.
White button Mushroom (WBM) (Agaricus bisporus) is a potential prostate cancer (PCa) chemo–preventative and therapeutic agent.
anti-cancer effects of phenolic–rich Extracts of Button Mushrooms (Agaricus bisporus)
In Summary, phenol-rich button Mushroom extracts inhibited prostate cancer cell growth in vitro, and caused apoptosis and cell cycle arrest. There was significant modulation of anti-proliferative genes by BBEA. These effects appear to be mediated in part by BBEA-induced oxidative stress. My present research provided the data to support the anti-cancer effects of button Mushrooms and provides preliminary data for future mechanistic studies.
AB showed potent antioxidant effect in an in-vitro assay. It was powerful as radical scavenger, reducing agent, metal chelator and inhibitor for lipid peroxidation. AB has been tested on Alzheimer‘s disease (AD) in particular on its antioxidant potential and on AD brain in AlCl3 modal.
Agaricus blazei Murrill
Agaricus blazei Murrill (ABM) popularly known as ‘Cogumelo do Sol’ in Brazil, or ‘Himematsutake’ in Japan, is a Mushroom native to Brazil, and widely cultivated in Japan for its Medicinal uses, so it is now considered as one of the most important edible and culinary–Medicinal biotechnological species. It was traditionally used to treat many common diseases like atherosclerosis, hepatitis, hyperlipidemia, diabetes, dermatitis and cancer. In vitro and in vivo ABM has shown immunomodulatory and antimutagenic properties, although the biological pathways and chemical substances involved in its pharmacological activities are still not clear. The polysaccharides phytocomplex is thought to be responsible for its immunostimulant and antitumor properties, probably through an opsonizing biochemical pathway. Clinical studies are positive confirmations, but we are still at the beginning, and there are perplexing concerns especially relative to the content of agaritine. Argantine is a well-known carcinogenic and toxic substance in animals, that must be completely and fully evaluated.
Agaricus blazei Murrill (“Kawariharatake” in Japan, “Cogmelo de Deus” in Brazil) was first discovered in Florida, USA, in 1944. Its main natural habitat is the mountainous district of Piedade in Sao Paulo, Brazil. It was found that the rate of occurrence of adult diseases in the Piedade region is extremely low since people took A. blazei as a part of their regular diet. The miracle Mushroom was brought to Japan in 1965, an artificial cultivation process was established in 1978, and it has been well evaluated in terms of biochemical and Medicinal properties since the 1980s. Many animal studies and clinical experience have demonstrated that A. blazei shows antitumor activity, immunological enhancement, and also the fungus is effective for treatment of AIDS, diabetes, hypotension, and hepatitis.
effects of the Medicinal Mushroom Agaricus blazei Murill on Immunity, Infection and cancer
Agaricus blazei Murill (AbM) is an edible, Medicinal Mushroom of Brazilian origin. It is used traditionally against a range of diseases, including cancer and chronic hepatitis, and has been cultivated commercially for the health food market. AbM has recently been shown to have strong immunomodulating properties, which has led to increasing scientific interest. In this article, we review current knowledge as to the immunological properties of AbM, and its possible clinical use in connection with infections and cancer. We also present some novel findings, which point to highly different biological potency between AbM extracts of different source and manufacturing.
Laccase from the Medicinal Mushroom Agaricus blazei: production, purification and characterization
The Medicinal Mushroom Agaricus blazei produced high amounts of laccase (up to 5,000 units l−1) in a complex, agitated liquid medium based on tomato juice, while only traces of the enzyme (<100 units l−1) were detected in synthetic glucose-based medium. Purification of the enzyme required three chromatographic steps, including anion and cation exchanging. A. blazei laccase was expressed as a single protein with a molecular mass of 66 kDa and an isoelectric point of 4.0. Spectroscopic analysis of the purified enzyme confirmed that it belongs to the “blue copper oxidases”. The enzyme’s pH optimum for 2,6-dimethoxyphenol (DMP) and syringaldazine was pH 5.5; but for 2,2′-azino-bis(3-ethylthiazoline-6-sulfonate) (ABTS) no distinct pH optimum was observed (highest activity at the lowest pH tested). Purified laccase was stable at 20°C, pH 7.0 and pH 3.0, but rapidly lost its activity at 40°C or pH 10. Sodium chloride strongly inhibited the enzyme activity, although the inhibition was completely reversible. The following kinetic constants were determined (Km, kcat): 63 μM, 21 s−1 for ABTS, 4 μM, 5 s−1 for syringaldazine, 1,026 μM, 15 s−1 for DMP and 4307 μM, 159 s−1 for guaiacol. The Results show that—in addition to the wood-colonizing white-rot Fungi—the typical litter-decomposing basidiomycetes can also produce high titers of laccase in suitable liquid media.
An extract of the Medicinal Mushroom Agaricus blazei Murill can protect against allergy
Conclusion
This particular AbM extract may both prevent allergy development and be used as a therapeutical substance against established allergy.
effect of an Extract Based on the Medicinal
Mushroom Agaricus blazei Murill on expression of
cytokines and Calprotectin in Patients with
ulcerative colitis and Crohn’s disease
An immunomodulatory extract (AndoSanÔ) based on the Medicinal mushroom Agaricus blazei Murill (AbM) has shown to reduce blood cytokine levels in healthy volunteers after 12 days’ ingestion, pointing to an anti-inflamma-tory effect. The aim was to study whether AndoSanÔ had similar effects on cytokines in patients with ulcerative colitis (UC) and Crohn’s disease (CD). Calprotectin, a marker for inflammatory bowel disease (IBD), was also mea- sured. Patients with CD (n = 11) and with UC (n = 10) consumed 60 ml ⁄ day of AndoSanÔ. Patient blood plasma was harvested before and after 6 h LPS (1 ng ⁄ ml) stimulation ex vivo. plasma and faecal calprotectin levels were analy-sed using ELISA and 17 cytokines [IL-2, IFN-c, IL-12 (Th1), IL-4, IL-5, IL-13 (Th2), IL-7, IL-17, IL-1b, IL-6, TNF-a, IL-8, MIP-1b, MCP-1, G-CSF, GM-CSF and IL-10] by multiplex assay. After 12 days’ ingestion of Ando- SanÔ, baseline plasma cytokine levels in UC was reduced for MCP-1 (40%) and in LPS-stimulated blood for MIP-1b (78%), IL-6 (44%), IL-1b (41%), IL-8 (30%), G-CSF (29%), MCP-1 (18%) and GM-CSF (17%). There were corresponding reductions in CD: IL-2 (100%), IL-17 (55%) and IL-8 (29%) and for IL-1b (35%), MIP-1b (30%), MCP-1 (22%), IL-8 (18%), IL-17 (17%) and G-CSF (14%), respectively. Baseline concentrations for the 17 cytokines in the UC and CD patient groups were largely similar. Faecal calprotectin was reduced in the UC group. Ingestion of an AbM-based Medicinal Mushroom by patients with IBD resulted in interesting anti-inflammatory effects as demon- strated by declined levels of pathogenic cytokines in blood and calprotectin in faeces
An immunostimulatory extract based on the Medicinal Mushroom Agaricus blazei Murill (AbM) has been shown to stimulate mononuclear phagocytes in vitro to produce pro-inflammatory cytokines, and to protect against lethal peritonitis in mice. The present aim was to study the effect of AbM on release of several cytokines in human whole blood both after stimulation ex vivo and in vivo after oral intake over several days in healthy volunteers. The 17 signal substances examined were; T helper 1 (Th1) cytokines [interleukin (IL)-2, interferon (IFN)-γ and IL-12], T helper 2 cytokines (IL-4, IL-5 and IL-13), pleiotropic (IL-7, IL-17), pro-inflammatory [IL-1β, IL-6, tumour necrosis factor (TNF)-α (mainly produced by Th1 cells)] – and anti-inflammatory (IL-10) cytokines, chemokines [IL-8, macrophage inhibitory protein (MIP)-1β and monocyte chemoattractant protein (MCP)-1] and leukocyte growth factors [granulocyte colony-stimulating factor (G-CSF), granulocyte/macrophage colony stimulating factor]. After stimulation of whole blood ex vivo with 0.5–5.0% of a Mushroom extract, AndoSan™ mainly containing AbM, there was a dose-dependent increase in all the cytokines studied, ranging from two to 399-fold (TNF-α). However, in vivo in the eight volunteers who completed the daily intake (60 ml) of this AbM extract for 12 days, a significant reduction was observed in levels of IL-1β (97%), TNF-α (84%), IL-17 (50%) and IL-2 (46%). Although not significant, there was a trend towards reduced levels for IL-8, IFN-γ and G-CSF, whilst those of the remaining nine cytokines tested, were unaltered. The discrepant Results on cytokine release ex vivo and in vivo may partly be explained by the antioxidant activity of AbM in vivo and limited absorption of its large, complex and bioactive β-glucans across the intestinal mucosa to the reticuloendothelial system and blood.
The Mushroom Agaricus blazei is studied for its nutraceutical potential and as a Medicinal supplement. The aim of the present study was to investigate the chemoprotective effect of β-glucan extracted from the Mushroom A. blazei against DNA damage induced by benzo[a]pyrene (B[a]P), using the comet assay (genotoxicity) and micronucleus assay with cytokinesis block (mutagenicity) in a human hepatoma cell line (HepG2). To elucidate the possible β-glucan mechanism of action, desmutagenesis or bioantimutagenesis types, three treatment protocols were tested: simultaneous, pre-treatment, and presimultaneous. The Results showed that β-glucan does not exert genotoxic or mutagenic effect, but that it does protect against DNA damage caused by B[a]P in every protocol tested. The data suggest that β-glucan acts through binding to B[a]P or the capture of free radicals produced during its activation. On the other hand, the pre-treatment Results also suggest the possibility that β-glucan modulates cell metabolism.
The edible Mushroom Agaricus blazei Murill (AbM), which has been used in traditional medicine against a range of diseases and possess immunomodulating properties, probably due to its high content of β-glucans. Others and we have demonstrated stimulatory effects of extracts of this Mushroom on different immune cells. Dendritic cells are major directors of immune function. We wanted to examine the effect of AbM stimulation on signal substance release from monocyte-derived dendritic cells (MDDC). After 6 d incubation with IL-4 and GM-CSF, the cells were true MDDC. Then the cells were further incubated with up to 10% of the AbM-based extract, AndoSan™, LPS (0.5 μg/ml) or PBS control. We found that the AbM extract promoted dose-dependent increased levels of IL-8, G-CSF, TNFα, IL-1β, IL-6 and MIP-1β, in that order. The synthesis of IL-2, IL-8 and IFNγ were similar for the AbM extract and LPS. However, AndoSan™ induced a 10- to 2-fold higher production than did LPS of G-CSF, TNFα and IL-1β, respectively. AbM did not induce increased synthesis of Th2 or anti-inflammatory cytokines or the Th1 cytokine IL-12. We Conclude that stimulation of MDDC with an AbM-based extract resulted in increased production of proinflammatory, chemotactic and some Th1-type cytokines in vitro.
Agaricus brasiliensis
The Royal Sun Medicinal Mushroom, Agaricus brasiliensis, is used as a natural health product. In Japan, however, the quality control of some of these Mushroom products has been viewed as a safety problem. Focusing on the quality control of A. brasiliensis KA21, we have performed several safety studies. To date, we have established evidence that this Mushroom can be used safely as an immunostimulant and to mediate biochemical parameters associated with obesity or diabetes. Furthermore, to improve the manufacturing process of this Mushroom, we have studied the relationship between its pharmaceutical actions and the conditions of its cultivation and thermal management. The purpose of this review is to report the findings of basic and clinical studies of the fruit body of A. brasiliensis KA21.
A process for simultaneous efficient production of bioactive polysaccharide and ergosterol by fed-batch fermentation of Medicinal Mushroom Agaricus brasiliensis was developed. effects of carbon source and initial sugar concentration on the production of extracellular polysaccharide (EPS) and ergosterol were studied at first. Sucrose was suitable for EPS production although the cells could not grow well. glucose was beneficial for the cell growth and production of ergosterol. When the initial glucose concentration exceeded 40 g/l, the ergosterol accumulation was decreased slightly. A repeated fed-batch fermentation strategy with glucose as carbon source, which feeding of glucose was commenced to 15 g/l from 72 to 120 h at 24 h intervals when the total glucose concentration of the broth was below 15 g/l in 7 l stirred bioreactor, was developed successfully to increase simultaneously EPS and ergosterol production. The maximum EPS and ergosterol production were 1.67 ± 0.08 g/l and 2.50 ± 0.04 mg/100 mg DW on 144 h, respectively, which were 26.9% and 17.2% higher than those by batch fermentation in the same cultivation conditions. It was the first reported to product simultaneously EPS and ergosterol in agitated fermentation of A. brasiliensis.
Agaricus campestris
Many species of edible Mushrooms are known to contain a wide array of compounds with high nutritional and Medicinal values. However, these values vary widely among Mushroom species because of the wide diversity of compounds with different solubilities to solvents used in extraction. We report here the comparison of antioxidant activity and cytotoxicity against cancer cells in extracts of Pleurotus ostreatus, P. sajor-caju, Agaricus campestris, and A. bisporus from 7 different solvents, including water, ethanol, ethyl acetate, acetone, chloroform, hexane, and petroleum ether. The extracts were analyzed for their antioxidant activities using the % DPPH (2,2-diphenyl-1-picrylhydrazylhydrate) scavenging activity method. Our Results revealed that the water extracts exhibited the highest % DPPH scavenging activity in comparison to all other solvent extracts. The highest value was obtained from the water extract of P. sajor-caju (78.1%), and the lowest one was from the hexane extract of A. bisporus (0.8%). In general, extracts from nonpolar solvents exhibited much lower antioxidant activities than those from polar solvents. The cytotoxic effects of these extracts were evaluated using 2 cancer cell lines of larynx carcinoma (HEp-2) and breast carcinoma (MCF-7). When added into Hep-2 cells, the hexane extracts from P. ostreatus, P. sajor-caju, A. bisporus, and A. campestris yielded the highest IC50 values of 1.7 ± 1.56, 2.1 ± 2.82, 4.4 ± 1.71, and 2.2 ± 1.34 μg/mL, respectively, in comparison to all other solvent extracts. Similar IC50 values were obtained when the MCF-2 cancer cells were tested, suggesting that hexane is the preferred solvent to extract the anticancer compounds from these Mushrooms. Our Results also indicated that extracts from solvents with nonpolar or intermediate polarity were more potent than those with high polarity in their cytotoxicity against cancer cells, and extracts from different Mushrooms by the same solvent possessed varied degrees of cytotoxicity.
Insulin-releasing and insulin-like activity of
Agaricus campestris (Mushroom)
Agaricus campestris (Mushroom) has been documented as a traditional treatment for diabetes. Here the administration of Mushroom in the diet (62·5 g/kg) and drinking water (2·5 g/l) countered the hyperglycaemia of streptozotocin- diabetic mice. An aqueous extract of Mushroom (1 mg/ ml) stimulated 2-deoxyglucose transport (2·0-fold), glucose oxidation (1·5-fold) and incorporation of glucose into glycogen (1·8-fold) in mouse abdominal muscle. In acute 20 min tests, 0·25–1 mg/ml aqueous extract of Mushroom evoked a stepwise 3·5- to 4·6-fold stimulation of insulin secretion from the BRIN-BD11 pancreatic B-cell line. This effect was abolished by 0·5 mM diazoxide and prior exposure to extract did not affect subsequent stimulation of insulin secretion by 10 mM -alanine, thereby negating a detrimental effect on cell viability. The effect of extract was potentiated by 16·7 mM glucose, -alanine (10 mM) and IBMX (1 mM), and a depolarising concentration of KCl (25 mM) did not augment the insulin-releasing activity of Mushroom. activity of the extract was found to be heat stable, acetone soluble and unaltered by exposure to alkali, but decreased with exposure to acid. Dialysis to remove components with molecular mass <2000 Da caused a 40% reduction in activity. Sequential extraction with solvents revealed insulin-releasing activity to be greatest in polar fractions. Lack of haemagglutinin activity with extract activity indicated that activity was unlikely to be due to a lectin-mediated event. These Results demonstrate the presence of antihyperglycaemic, insulin-releasing and insulin-like activity in A. campestris.
COMPARATIVE ANALYSIS OF polyphenolic PROFILES
AND antioxidant activity OF
Agaricus bisporus AND Agaricus campestris
In the context of a worldwide growing population there is a need for renewable biological resources for food and animal feed, safe and healthy, as well as materials, energy and other products. Thus, an important and sustainable use of renewable resources has become one of the major goals of bio-economic strategy at the national and European levels. Quality, food safety and human health are some of the major concerns of Romania. Due to considerable genetic resources and remarkable biological quality, Mushrooms are currently considered functional foods with important nutritional and therapeutic qualities. Nationally, 90% of the Mushroom production is covered by Agaricus bisporus species (champignon), being consumed mainly in urban areas. At the same time in rural areas is harvested from spontaneous mycoflora and consumed, mainly Agaricus campestris species. These two species are related, belonging to the same Agaricaeae family. nutritional and therapeutic important properties of these species are given by their bioactive metabolites including polysaccharides, proteins, dietary fibres, polyphenolic compounds and other bio- molecules. In this paper is presented comparative qualitative (HPTLC) and quantitative (spectrophotometric) chemical composition in polyphenolic compounds and the scavenger potential of free radical DPPH of the two species. The comparative analysis is made for alcoholic and hydroalcoholic extracts of the two species. The Results shows the differences and similarities in terms of composition in polyphenolic compounds, dependence between chemical composition and antioxidant potential and also the importance of the solvent used to obtain the extracts. Thus, this study contributes to understanding the importance of the valorisation of indigenous natural resources potential, respectively of the species Agaricus campestris.
Agaricus subrufescens
Agaricus subrufescens, a cultivated edible and Medicinal Mushroom, and its synonyms
Agaricus subrufescens Peck was cultivated first in the late 1800s in eastern North America. The type consists partly of cultivated material and partly of field-collected specimens. Once a popular market Mushroom, the species faded from commerce in the early 20th century. More recently, a Mushroom species growing wild in Brazil has been introduced into cultivation in Brazil, Japan and elsewhere. This Brazilian Mushroom has been referred to by various names, most commonly as A. blazei Murrill (sensu Heinemann) and most recently as A. brasiliensis Wasser et al. The author first cultivated A. subrufescens in 1981 and has grown and studied Brazilian isolates since 1992. The species has an amphithallic pattern of reproduction. Based on DNA sequence analysis of the rDNA ITS region and on mating studies and genetic analysis of hybrid progeny, there is a strong case for conspecificity of the Brazilian Mushrooms with A. subrufescens. Based on a study of the type and other data, the recent lectotypification of A. subrufescens is accepted. Data are presented on Mushrooms of diverse geographical origins, including A. rufotegulis Nauta from western Europe, another apparent con-specific. A possible role for interpopulational hybridization in current populations of A. subrufescens is proposed. The agronomic history of the species is reviewed.
Agaricus subrufescens: A review
Medicinal Mushrooms have currently become a hot issue due to their various therapeutic properties. Of these, Agaricus subrufescens, also known as the “almond Mushroom”, has long been valued by many societies (i.e., Brazil, China, France, and USA). Since its discovery in 1893, this Mushroom has been cultivated throughout the world, especially in Brazil where several strains of A. subrufescens have been developed and used as health food and alternative medicine. This article presents up-to-date information on this Mushroom including its taxonomy and health promoting benefits. Medicinal properties of A. subrufescens are emphasized in several studies which are reviewed here. In addition, safety issues concerning the use of this fungus will be discussed.
Agaricus subrufescens, a cultivated edible and Medicinal Mushroom, and its synonyms
Agaricus subrufescens Peck was cultivated first in the late 1800s in eastern North America. The type consists partly of cultivated material and partly of field-collected specimens. Once a popular market Mushroom, the species faded from commerce in the early 20th century. More recently, a Mushroom species growing wild in Brazil has been introduced into cultivation in Brazil, Japan and elsewhere. This Brazilian Mushroom has been referred to by various names, most commonly as A. blazei Murrill (sensu Heinemann) and most recently as A. brasiliensis Wasser et al. The author first cultivated A. subrufescens in 1981 and has grown and studied Brazilian isolates since 1992. The species has an amphithallic pattern of reproduction. Based on DNA sequence analysis of the rDNA ITS region and on mating studies and genetic analysis of hybrid progeny, there is a strong case for conspecificity of the Brazilian Mushrooms with A. subrufescens. Based on a study of the type and other data, the recent lectotypification of A. subrufescens is accepted. Data are presented on Mushrooms of diverse geographical origins, including A. rufotegulis Nauta from western Europe, another apparent con-specific. A possible role for interpopulational hybridization in current populations of A. subrufescens is proposed. The agronomic history of the species is reviewed.
In the past decades many papers were published on the nutritional effect and bioactive components of edible Mushrooms. The Fungi are able to accumulate secondary metabolites, for example, phenolic compounds, polyketides, terpenes and steroids. In case of Mushrooms the button Mushrooms are preferred in the Eastern-European region. Therefore white and cream type button Mushroom (Agaricus bisporus) and different A. subrufescens (syn. A. blazei) cultivars were cropped, total phenolic content and antioxidant capacity (FRAP) were measured in two years of experiments. To develop the description method of Mushroom products, software-supported profile analysis was applied to characterize them. The aim of the research was to compare the sensory profiles of the samples, and to find those characteristics, they actually differ in.
In vitro cytotoxicity and antioxidant activity of Agaricus
subrufescens extracts
Agaricus blazei Murill, most recently referred as Agaricus subrufescens is a fungus that belongs to the Brazilian diversity and, considered as an important producer of bioactive compounds beneficial to human health. Studies have demonstrated that these compounds present immunomodulatory, antioxidant and antitumor properties. However, there is little information about the appropriate methodology for obtaining extracts with biological activities and their possible citotoxicity. The Mushroom extracts were evaluated by cytotoxicity assays using primary cultures of granulocytes and macrophages colony forming cells (CFU-GM) and established V79 cell line. Lipoperoxidation analysis using fibroblast V79 cells were also conducted. The extract fraction that produced a crystalline product was obtained from the alcoholic extraction at 60°C. This fraction exhibited an antioxidant activity on mitochondrial membranes and did not present cytotoxic activity on concentrations lower than 2.5 mg/mL in both cells systems evaluated CFU-GM and V79. Moreover, no significant alterations on the fibroblast V79 adhesion or proliferation capacity was observed. We suggest that the alcoholic fraction obtained from A. subrufescens at 60°C has a great potential for biotechnological application since it is easily obtained and presented low cytotoxicity potential.
photoprotective and antimutagenic activity of Agaricus subrufescens Basidiocarp Extracts
The photoprotective and antimutagenic activity of opened and closed basidiocarps of Agaricus subrufescens (=A. blazei; =A. brasiliensis) obtained by different extraction methods were evaluated on Aspergillus nidulans conidia submitted to ultraviolet (UV) light. The aqueous extracts were obtained by three extraction methods: maceration, infusion, and decoction, at two different extraction times. The extracts of A. subrufescens did not present toxicity for A. nidulans conidia. A suspension of A. nidulans conidia was submitted to extracts before and after the exposure to UV light. All basidiocarp extracts, regardless of the extraction method or development stage, protected A. nidulans conidia against the damaging effects of the mutagenic agent. The antimutagenic and photoprotective activity was strengthened with extracts obtained by 168-h maceration, followed by 24-h maceration and 60-min infusion and, at last, by 30-min infusion. Although the extracts presented protector effect as well as recoverer effect to the action of UV light, the preventive effect was more evident. Differences in the biological activity in function of the different development stages were detected with greater antimutagenic and photoprotective activity for the opened basidiocarps. However, the extraction method is the most important factor to be considered when compared to the basidiocarp development stage to obtain better antimutagenic and photoprotective activity of A. subrufescens basidiocarps.
In this work, the inhibitory activity of a wide range of polysaccharide extracts from two Iranian and French strains of Agaricus subrufescens were evaluated toward acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Among them, two extracts S9 and S′7 obtained from Iranian and French strains under different extraction conditions showed selective AChE inhibitory activity with IC<sub>50</sub> values of 154.63 and 145.43 μg/mL, respectively. It should be noted that all extracts from both strains demonstrated no BChE inhibitory activity. S9 and S′7 were also tested for their effect on amyloid beta (Aβ) aggregation, antioxidant activity, and neuroprotectivity. Their activity against Aβ aggregation was comparable to that of donepezil as the reference drug but they induced moderate antioxidant activity by DPPH radical scavenging activity and negligible neuroprotectivity against Aβ-induced damage.
Agaricus villaticus
It has the effects of anti-oxidation, anti-tumor activity, anti-bacterial, blood nourishing, spirit benefiting, liver tonifying and five zang organs tonifying
Mushrooms of the genus Agaricus as functional foods
Mushrooms of the genus Agaricus are noted for their pharmacological and culinary properties. In this study, it was performed a critical literature review, focusing primarily on aspects of the chemical composition of these mushrooms whose pharmacological properties and nutri- tional composition characterize them as functional foods. It was also discussed articles conducted in vitro and in vivo proving the high antioxidant potential of the A^ari- caceae family, in addition to articles which emphasize the toxicity characteristics and safety for its use in therapy or in human nutrition. These mushrooms exhibit numerous bioactive substances as well as safety regarding toxicity, which characterize them as functional foods. Despite the countless beneficial effects on human health, mushrooms of the genus Agaricus are little known by the population, making it necessary partnership and combined efforts among producers, industries and researchers in order to
disseminate, research and consumption of these foods
Agrocybe aegerita
antidiabetic and antioxidant activities of Eight Medicinal Mushroom species from China
The objective of the current study was to verify antidiabetic effects of different types of Mushrooms as folk medicines in treating diabetes. The antidiabetic effects were evaluated by in vitro α-glycosidase and aldose reductase (AR) inhibitory assays and antioxidant activity assay. Ganoderma lucidum extract exhibited the best dose-dependent inhibitory activity against α-glycosidase with IC50 at 4.88 mg/mL, and also exhibited aldose reductase inhibitory potential with IC50 value of 9.87 mg/mL. Tremella fuciformis demonstrated the highest AR inhibitory activity (IC50=8.39 mg/mL). antioxidant activities of selected Mushrooms were evaluated based on the total phenolic content (TPC), total flavonoids content (TFC), and DPPH free radical scavenging activity. The result showed that G. lucidum contained the highest TPC (39.3 mg GAE/g sample extract), TFC (15.1 mg CE/g sample extract), and the strongest DPPH free radical scavenging activity (IC50=3.66 mg/mL) among the Mushroom samples.
Amanita Caesarea
Mushrooms are macro Fungi that exist everywhere around us. They have significant roles in human health–life as source of nutrition and bioactive compounds. Many edible Mushrooms have been reported as promising biotechnological tools for production of secondary metabolites of various biological activities. The genus macrolepiota; Russula; Amanita; Vovariella and Grifola are a group of edible Mushrooms that are distributed all over the world. The studies on different species of these edible Mushrooms have revealed their nutritional Medicinal potentials. This review aims to present the importance of the genera macrolepiota; Russula; Amanita; Vovariella and Grifola as both food and medicine, and they offer new insights to researchers to develop new drugs and nutraceuticals.
Amauroderma rude
Medicinal Mushrooms in recent years have been the subject of many experiments searching for anticancer properties. We previously screened thirteen Mushrooms for their potential in inhibiting tumor growth, and found that the water extract of Amauroderma rude exerted the highest activity. Previous studies have shown that the polysaccharides contained in the water extract were responsible for the anticancer properties. This study was designed to explore the potential effects of the polysaccharides on immune regulation and tumor growth. Using the crude Amauroderma rude extract, in vitro experiments showed that the capacities of spleen lymphocytes, macrophages, and natural killer cells were all increased. In vivo experiments showed that the extract increased macrophage metabolism, lymphocyte proliferation, and antibody production. In addition, the partially purified product stimulated the secretion of cytokines in vitro, and in vivo. Overall, the extract decreased tumor growth rates. Lastly, the active compound was purified and identified as polysaccharide F212. Most importantly, the purified polysaccharide had the highest activity in increasing lymphocyte proliferation. In Summary, this molecule may serve as a lead compound for drug development.
We have previously screened thirteen Medicinal Mushrooms for their potential anti-cancer activities in eleven different cell lines and found that the extract of Amauroderma rude exerted the highest capacity in inducing cancer cell death. The current study aimed to purify molecules mediating the anti-cancer cell activity. The extract of Amauroderma rude was subject to fractionation, silica gel chromatography, and HPLC. We purified a compound and identified it as ergosterol by EI-MS and NMR, which was expressed at the highest level in Amauroderma rude compared with other Medicinal Mushrooms tested. We found that ergosterol induced cancer cell death, which was time and concentration dependent. In the in vivo experiment, normal mice were injected with murine cancer cell line B16 that is very aggressive and caused mouse death severely. We found that treatment with ergosterol prolonged mouse survival. We found that ergosterol–mediated suppression of breast cancer cell viability occurred through apoptosis and that ergosterol up-regulated expression of the tumor suppressor Foxo3. In addition, the Foxo3 down-stream signaling molecules Fas, FasL, BimL, and BimS were up-regulated leading to apoptosis in human breast cancer cells MDA-MB-231. Our Results suggest that ergosterol is the main anti-cancer ingredient in Amauroderma rude, which activated the apoptotic signal pathway. ergosterol may serve as a potential lead for cancer therapy.
Amauroderma rugosum
Amauroderma rugosum is one of the traditional Chinese Medicinal Mushrooms and is used to reduce inflammation, treat diuretic and upset stomach, and prevent cancer. Here, we present a genomic resource of Amauroderma rugosum (ACCC 51706) for further understanding its biology and exploration of the synthesis pathway of bioactive compounds. Genomic DNA was extracted and then subjected to Illumina HiSeq X Ten and PacBio Sequel I sequencing. The final genome is 40.66 Mb in size, with an N50 scaffold size of 36.6 Mb, and encodes 10 181 putative predicted genes. Among them, 6931 genes were functionally annotated. Phylogenomic analysis suggested that A. rugosum and Ganoderma sinense were not clustered together into a group and the latter was grouped with the Polyporaceae. Further, we also identified 377 carbohydrate-active enzymes (CAZymes) and 15 secondary metabolite biosynthetic gene clusters. This is the first genome-scale assembly and annotation for an Amauroderma species. The identification of novel secondary metabolite biosynthetic gene clusters would promote pharmacological research and development of novel bioactive compounds in the future.
Antrodia camphorata
terpenoids from the Medicinal Mushroom Antrodia camphorata: chemistry and Medicinal potential
Antrodia camphorata is a Medicinal Mushroom endemic to Taiwan for the treatment of intoxication, liver injury, cancer, and inflammation. Owing to its rare occurrence and potent pharmacological activities, efforts have been devoted to identify its bioactive constituents, especially terpenoids. Since 1995, a total of 162 terpenoids including triterpenoids, meroterpenoids, sesquiterpenoids, diterpenoids, and steroids have been characterized. The ergostane-type triterpenoids (antcins) and meroterpenoids (antroquinonols) are characteristic constituents of A. camphorata. The terpenoids show anti-cancer, hepatoprotective, anti-inflammatory, anti-diabetic, and neuroprotective activities. This review summarizes the research progress on terpenoids in A. camphorata during 1995–2020, including structural diversity, resources, biosynthesis, pharmacological activities, metabolism, and toxicity. The Medicinal potential of the terpenoids is also discussed.
Ergostanes are major bioactive constituents of the Medicinal Mushroom Antrodia camphorata. These tetracyclic triterpenoids usually occur as 25R/S epimeric pairs, which renders their chromatographic separation difficult. In this study, we used analytical supercritical-fluid chromatography (SFC) to separate seven pairs of 25R/S-ergostanes from A. camphorata. The (R)- and (S)-forms for each of the seven pairs could be well resolved (Rs > 1.3) on a Chiralcel OJ-H column (4.6 × 250 mm, 5 μm, chiral), eluted by 10% MeOH in CO2 at 2 mL/min with a back pressure of 120 bar and a column temperature of 40 °C. Particularly, this chiral-SFC method could rapidly and efficiently separate low-polarity epimers like antcin A and antcin B, which were very difficult for RP-HPLC. A 3-min preparative-scale method was established to purify (25S)- and (25R)-antcin A for the first time. However, OJ-H column suffered from peak overlapping of different pairs of ergostanes. We found that Princeton 2-ethylpyridine column (2-EP, 4.6 × 250 mm, 3 μm, achiral) could effectively separate different pairs, although the resolutions for 25-R/S forms of each epimeric pair were not as good as OJ-H column. Meanwhile, all the (25S)-forms showed stronger retentions than the corresponding (25R)-epimers on the 2-EP column. These Results demonstrated different selectivity of chiral- and achiral-SFC in separating 25R/S-ergostane epimers. Aside from high separation efficiency, SFC also showed advantage over HPLC in short analysis time and low consumption of organic solvents. Finally, both OJ-H and 2-EP columns were used on analytical SFC to separate 25R/S-ergostanes in an extract of A. camphorata.
Antrodia camphorata is an extremely rare fungus native to the forested regions of Taiwan. It is also a traditional Chinese medicine, and Taiwanese aborigines applied it for treating liver diseases and protecting from food and drug intoxication. Scientific studies have demonstrated that A. camphorata crude extracts and pure compounds possess a variety of beneficial functions, such as anti-hypertensive, anti-hyperlipidemic, anti-inflammatory, anti-oxidant, anti-tumor, and immuno-modulatory activities. Recent studies have shown that many of these biological and pharmacological activities can be attributed to various active constituents, including polysaccharides, terpenoids, steroids, lignans, benzoquinone derivatives, benzenoids, and maleic and succinic acid derivatives. A. camphorata has been considered as a novel phytotherapeutic agent. However, detailed mechanistic studies or even clinical trials on A. camphorata are still rare. With the help of modern analytical techniques, it is not surprising that many novel constituents are being identified or fractionated from A. camphorata mycelium and fruiting bodies. This review summarizes the latest published Results from A. camphorata research, focusing on the biological and pharmacological activities of the crude extract and known constituents of A. camphorata.
Antrodia cinnamomea
edible and Medicinal Mushrooms have usually been considered as a sustainable source of unique bioactive metabolites, which are valued as promising provisions for human health. Antrodia cinnamomea is a unique edible and Medicinal fungus widespread in Taiwan, which has attracted much attention in recent years for its high value in both scientific research and commercial applications owing to its potent therapeutic effects, especially for its hepatic protection and anticancer activity. Due to the scarcity of the fruiting bodies, the cultivation of A. cinnamomea by submerged fermentation appears to be a promising substitute which possesses some unique advantages, such as short culture time period and its high feasibility for scale-up production. However, the amount of fungal bioactive metabolites derived from the cultured mycelia of A. cinnamomea grown by submerged fermentation is much less than those obtained from the wild fruiting bodies. Hence, there is an urgent need to bridge such a discrepancy on bioactive metabolites between the wild fruiting bodies and the cultured mycelia. The objective of this article is to review recent advances and the future development of the mycelial submerged fermentation of A. cinnamomea in terms of enhancement for the production of fungal bioactive components by the optimization of culture conditions and the regulation of fungal metabolism. This review provides valuable information for further biotechnological applications of A. cinnamomea as well as other Mushrooms being the source of bioactive ingredients by submerged fermentation.
Current evidence for the hepatoprotective activities of the Medicinal Mushroom Antrodia cinnamomea
Antrodia cinnamomea (AC) is an endemic Mushroom species of Taiwan, and has been demonstrated to possess diverse biological and pharmacological activities, such as anti-hypertension, anti-hyperlipidemia, anti-inflammation, anti-oxidation, anti-tumor, and immunomodulation. This review focuses on the inhibitory effects of AC on hepatitis, hepatocarcinoma, and alcohol-induced liver diseases (e.g., fatty liver, fibrosis). The relevant biochemical and molecular mechanisms are addressed. Overall, this review summarizes the hepatoprotective activities in vitro and in vivo. However, there is no doubt that human and clinical trials are still limited, and further studies are required for the development of AC-related products.
In recent years, Antrodia cinnamomea has attracted great attention around the world as an extremely precious edible and Medicinal Mushroom. Ubiquinone derivatives, which are characteristic metabolites of A. cinnamomea, have shown great bioactivities. Some of them have been regarded as promising therapeutic agents and approved into clinical trial by US FDA. Although some excellent reviews have been published covering different aspects of A. cinnamomea, this review brings, for the first time, complete information about the structure, bioactivity, chemical synthesis, biosynthesis and metabolic regulation of ubiquinone derivatives in A. cinnamomea. It not only advances our knowledge on the bioactive metabolites especially the ubiquinone derivatives in A. cinnamomea, but also provides valuable information for the investigation on other edible and Medicinal Mushrooms.
Antrodia cinnamomea is an extremely rare and endemic fungal species native to forested regions of Taiwan. In modern Taiwanese culture, A. cinnamomea is believed to be a valuable gift from the heaven. Thereby, it is claimed as the “National Treasure of Taiwan” and “Ruby” among Mushrooms.” Traditionally, A. cinnamomea was used to prepare Chinese medicine for treating various illness including liver diseases, food and drug intoxication, diarrhea, abdominal pain, hypertension, itchy skin, and tumorigenic diseases. Recent scientific studies strongly support that the pharmacological activities of A. cinnamomea go far beyond the original usage, as A. cinnamomea has exhibited various pharmacological properties including anticancer, antioxidant, hepatoprotection, antihypertensive, antihyperlipidemic, immunomodulatory, and anti-inflammatory properties. Till date, more than 400 scientific reports have been published on the therapeutic potential of A. cinnamomea, or its closely related species Antrodia salmonea, and their compounds. In the present review, the taxonomic description of A. cinnamomea, ethnomedical value, chemical constituents, and pharmacological effects particularly antioxidant and Nrf2-mediated cytoprotective effects will be discussed.
Antrodia salmonea
Antrodia salmonea (AS), a well-known medicinal mushroom in Taiwan, has been reported to exhibit anti-oxidant, anti-angiogenic, anti-atherogenic, and anti-inflammatory effects.
Antrodia salmonea (AS), a well-known medicinal mushroom in Taiwan, has been reported to exhibit anti-oxidant, anti-angiogenic, anti-atherogenic, and anti-inflammatory effects. In the present study, we investigated the activation of Nrf2-mediated antioxidant genes in RAW264.7 macrophages by the fermented culture broth of AS, studied the resulting protection against lipopolysaccharide (LPS)-stimulated inflammation, and revealed the molecular mechanisms underlying these protective effects. We found that non-cytotoxic concentrations of AS (25–100 μg mL−1) protected macrophages from LPS-induced cell death and ROS generation in a dose-dependent manner. The antioxidant potential of AS was directly correlated with the increased expression of the antioxidant genes HO-1, NQO-1, and γ-GCLC, as well as the level of intracellular GSH followed by an increase in the nuclear translocation and transcriptional activation of the Nrf2–ARE pathway. Furthermore, Nrf2 knockdown diminished the protective effects of AS, as evidenced by the increased production of pro-inflammatory cytokines and chemokines, including PGE2, NO, TNF-α, and IL-1β, in LPS-stimulated macrophages. Notably, AS treatment significantly inhibited LPS-induced ICAM-1 expression in macrophages. Our data suggest that the anti-inflammatory potential of Antrodia salmonea is mediated by the activation of Nrf2-dependent antioxidant defense mechanisms. Results support the traditional usage of this beneficial mushroom for the treatment of free radical-related diseases and inflammation.
Conclusions: Taken together, these results suggest that Antrodia salmonea may be useful for the prevention of angiogenesis and atherosclerosis.
Antrodia salmonea (AS) is a fungus, which belongs to a fungal family of Taiwanofungus salmoneus with the features of anti-oxidant, anti-inflammatory, and anticancer. Recent studies have shown that AS has anti-cancer functions in ovarian and breast cancer. However, the effects of AS on prostate cancer (PCa) proliferation remain unknown. Therefore, we investigated the role of AS in PCa proliferation through apoptosis, and cell cycle regulation in PCa cell lines. Our results showed that Antrodia salmonea extract (ASE) inhibited PCa cells growth with a dose-dependent manner. In addition, ASE decreased the anchorage-independent growth formation ability in PC3 cells. Moreover, ASE-induced cell growth inhibition in PCa cells (DU145, PC3) was correlated to decreased cell cycle-related proteins such as cyclin A/B and cyclin-dependent kinase CDK1/2/4, and increased cell cycle inhibitor proteins p21. Besides, ASE decreased the total protein level of epidermal growth factor receptor and its downstream signaling pathways Akt and Erk in both PCa cells. We found that apoptotic markers such as cleaved-PARP protein levels increased significantly in DU145 cells indicating ASE might induce apoptosis. In conclusion, our results suggest that ASE may have the ability to induce PCa cell death through regulating cell cycle arrest and apoptosis pathways.
Armillaria luteo-virens
Mushrooms have been valued as food and health supplements by humans for centuries. They are rich in dietary fiber, essential amino acids, minerals, and many bioactive compounds, especially those related to human immune system functions. Mushrooms contain diverse immunoregulatory compounds such as terpenes and terpenoids, lectins, fungal immunomodulatory proteins (FIPs) and polysaccharides. The distributions of these compounds differ among Mushroom species and their potent immune modulation activities vary depending on their core structures and fraction composition chemical modifications. Here we review the current status of clinical studies on immunomodulatory activities of Mushrooms and Mushroom products. The potential mechanisms for their activities both in vitro and in vivo were summarized. We describe the approaches that have been used in the development and application of bioactive compounds extracted from Mushrooms. These developments have led to the commercialization of a large number of Mushroom products. Finally, we discuss the problems in pharmacological applications of Mushrooms and Mushroom products and highlight a few areas that should be improved before immunomodulatory compounds from Mushrooms can be widely used as therapeutic agents.
wild edible macro Fungi Floccularia luteovirens proved to be a valuable source for the identification of novel lead molecules with therapeutic potential. Nevertheless, the chemical constituents of Floccularia luteovirens are rarely reported due to absence of efficient purification methods. In this study, a hydrophilic interaction chromatography directed by on-line HPLC-DPPH assay has been developed and successfully applied for the isolation of free radical inhibitor from the methanolic extract of Floccularia luteovirens. Using a hydrophilic interaction chromatographic column coupled with the HPLC-DPPH assay for screening the potential radical scavengers, the mid-pressure hydrophilic interaction chromatography (HILIC) proved to be more efficient in the pretreatment stage, yielding the fraction rich in free radical scavengers in good yield (5.9% recovery from 130.0 g of fresh F. luteovirens). From highly potent fraction, the target compound was isolated using the Click XION preparative chromatography with 17.2% recovery. The isolated compound was L-(+)-ergothioneine, where the purity (>95%) and antioxidant activity of were confirmed by chromatography and HPLC-DPPH assay, while the structure of this compound was elucidated from HR ESI-MS and NMR data. This method proved to be very efficient for the recognition and isolation of highly polar free radical inhibitors from Fungi extracts, and is also applicable for the purification of highly polar compounds from other sources.
Submerged Cultivation of Medicinal Mushrooms: Bioprocesses and Products
Medicinal Mushrooms belonging to higher Basidiomycetes are an immensely rich yet largely untapped resource of useful, easily accessible, natural compounds with various biological activities that may promote human well-being. The Medicinal properties are found in various cellular components and secondary metabolites (polysaccharides, proteins and their complexes, phenolic compounds, polyketides, triterpenoids, steroids, alkaloids, nucleotides, etc.), which have been isolated and identified from the fruiting bodies, culture mycelium, and culture broth of Mushrooms. Some of these compounds have cholesterol-lowering, anti-diabetic, antioxidant, antitumor, immunomodulating, antimicrobial, and antiviral activities ready for industrial trials and further commercialization, while others are in various stages of development. Recently, the submerged cultivation of Medicinal Mushrooms has received a great deal of attention as a promising and reproducible alternative for the efficient production of Mushroom mycelium and metabolites. Submerged cultivation of Mushrooms has significant industrial potential, but its success on a commercial scale depends on increasing product yields and development of novel production systems that address the problems associated with this technique of Mushroom cultivation. In spite of many researchers’ efforts for the production of bioactive metabolites by Mushrooms, the physiological and engineering aspects of submerged cultures are still far from being thoroughly studied. The vast majority of studies have focused on polysaccharide and ganoderic acid production in submerged cultivation of Medicinal Mushrooms, and very little has been written so far on the antioxidant and hemagglutinating activity of submerged Mushroom cultures. The purpose of this review is to provide an update of the present state of the art and future prospects of submerged cultivation of Medicinal Mushrooms to produce mycelium and bioactive metabolites, and to make a contribution for the research and development of new pharmaceutical products from Mushrooms. A brief overview of the metabolic diversity and bioactive compounds of Mushrooms produced by submerged cultures is also given.
In this study, the culture requirements of the Cerrena unicolor OBCC 5005 strain were determined to optimize bioactive exopolysaccharide production in submerged culture. The effects of initial medium pH, carbon and nitrogen sources, inoculum age and amount, and mineral source on exopolysaccharide and mycelial biomass production by the C. unicolor OBCC 5005 strain were studied using a one-factor-at-a-time method. The highest exopolysaccharide production was obtained when culture parameters were used as initial medium pH: 5.5, 5% sucrose, 5% mycological peptone, and 5% of 4-day inoculants in the presence of 5 mM Fe2+. Optimized culture conditions at a flask scale were applied to a 3-L stirred tank reactor. As a result, 7.92 g/L and 7.34 g/L maximum exopolysaccharide production in optimized conditions at flask and stirred-tank reactor scales were achieved, respectively. The present study is the first to prove that C. unicolor can yield high bioactive exopolysaccharide production at flask and stirred-tank reactor scales.
Mushroom lectins: Specificity, Structure and Bioactivity Relevant to human Disease
lectins are non-immunoglobulin proteins that bind diverse sugar structures with a high degree of selectivity. lectins play crucial role in various biological processes such as cellular signaling, scavenging of glycoproteins from the circulatory system, cell–cell interactions in the immune system, differentiation and protein targeting to cellular compartments, as well as in host defence mechanisms, inflammation, and cancer. Among all the sources of lectins, plants have been most extensively studied. However, more recently fungal lectins have attracted considerable attention due to their antitumor, antiproliferative and immunomodulatory activities. Given that only 10% of Mushroom species are known and have been taxonomically classified, Mushrooms represent an enormous unexplored source of potentially useful and novel lectins. In this review we provide an up-to-date Summary on the biochemical, molecular and structural properties of Mushroom lectins, as well as their versatile applications specifically focusing on Mushroom lectin bioactivity.
High Processing Tolerances of immunomodulatory Proteins in Enoki and Reishi Mushrooms
This study investigated the processing tolerances of two Mushroom proteins with immunomodulatory activities, including FVE from Enoki (Flammulia velutipes) and LZ8 from Reishi (Ganoderma lucidum) Mushrooms, under food processing treatments such as heating, sterilization, frozen storage, extraction in acid/alkaline conditions, and dehydration. Results showed that the capability of these two proteins to induce IFN-γ secretion by murine splenocytes remained after 100 °C heating for 30 min, 121 °C autoclaving for 15 min, and −80 °C freezing. The retained activities of both proteins on cell proliferation and IFN-γ production did not decrease at 0.6 M hydrochloric acid (at pH 2) but strikingly dropped at 5 M sodium hydrate (at pH 13). After vacuum dehydration, FVE and LZ8 retained most of their activities on cell proliferation; nevertheless, the IFN-γ secretion decreased to about half of the initial values. These findings suggest that these two Mushroom proteins have a good thermal/freezing resistance, acid tolerance, and dehydration stability and are candidates for processing in food and nutraceutical utilization.
Defense Proteins with antiproliferative and antimicrobial activities from Fungi and Bacteria
Defensins are a group of proteins characterized by a conservedcysteine-stabilized alpha-helix and beta-sheet structural motif. They are widely distributed among vertebrates and invertebrates. In addition to the presence of defensins in mammals and submammalian vertebrates enumerated in Chap. 23, Fungi and bacteria also produce a variety of defensins with antiproliferative activity toward tumor cells and anticancer activity in tumor bearing mice. The fungal proteins include ribonucleases, antifungal proteins, antibacterial proteins, ubiquitin-like peptides, ribosome inactivating proteins, hemolysins, hemagglutinins/lectins, laccases, and proteases. The bacterial proteins comprise ribonucleases and antifungal proteins. Some of the aforementioned proteins also display antimicrobial activities toward pathogenic microbes.
This study was to isolate the anti-leukaemic component from edible Mushroom Hypsizygus marmoreus (Peck) Bigelow. Crude protein was extracted from the basidioma, and then purified with DEAE-Sepharose CL-6B ion exchange chromatography followed by Sephacryl S-300 gel filtration. A protein which exerted high growth inhibitory effect on human leukaemic U937 cells and sufficient toxicological safety on normal human white blood cells was isolated and named HM-3A. Electrophoresis showed HM-3A approximately 52 kDa in size. N-terminal analysis found the amino acid sequence ATTQWKTSAA and confirmed HM-3A a novel protein. High-performance anion-exchange column chromatography revealed HM-3A a glycoprotein with galactose as the major monosaccharide. Haemagglutination assay proved it non-lectin. We suggest that HM-3A is worth further investigation for antitumour use.
lectins from Medicinal Plants: Characterizations and Biological properties
lectins are a group of carbohydrate-binding proteins of non-immune origin found in a diversity of organisms, plants, animals, Fungi, bacteria and virus with potent biological activity. The present chapter is an attempt to represent a multidisciplinary study on this lectins isolated from Medicinal plants like Nymphaea nouchali, Kaempferia rotunda, Kaempferia parviflora, Alisma orientale, Pinellia ternate and Phthirusa pyrifolia covering their purification process, information on hemagglutination activities and inhibition by sugars, as well as variation of stability with the change of temperature, pH and in presence of denaturants. Along with the toxicity of Kaempferia rotunda lectin and Nymphaea nouchali lectin against the brine shrimp nauplii, antibacterial activities of Kaempferia rotunda lectin, Nymphaea nouchali lectin, Eugenia uniflora L seeds lectin and Phthirusa pyrifolia leaf lectin, antiproliferative activities of Alisma orientale lectin, Pinellia ternate lectin, Kaempferia rotunda lectin, Nymphaea nouchali lectin and Pinellia ternate agglutinin against a number of cancer cell lines are described in brief.
Armillaria mellea (Vahl) P. Kumm
Armillaridin (AM) is an aromatic ester compound isolated from honey Medicinal Mushroom, Armillaria mellea, which has anti-cancer potential. This study was designed to examine the effects of AM on differentiation and activation macrophages, the major ontogeny of innate immunity. macrophages were derived from CD14+ monocytes which were sorted from human peripheral blood mononuclear cells. cell viability was assessed by trypan blue exclusion test. cells were stained with Liu’s dye for observation of morphology. expression of surface antigens was examined by flow cytometric analysis. Phagocytosis and generation of reactive oxygen species (ROS), as functional assays, were evaluated by counting engulfed yeasts and DCFH-DA reaction. The viability of macrophages was not significantly reduced by AM. AM at nontoxic concentrations markedly increased cytoplasmic vacuoles. The expression of surface CD14, CD16, CD36, and HLA-DR was suppressed. The phagocytosis function, but not ROS production, of macrophages was inhibited by AM. Armillaridin could inhibit the differentiation and activation of human macrophages. It may have potential to be developed as a biological response modifier for inflammatory diseases.
The basidiomycetous tree pathogen species Armillaria mellea (honey Mushroom) produces a large variety of structurally related antibiotically active and phytotoxic natural products, referred to as the melleolides. During their biosynthesis, some members of the melleolide family of compounds undergo monochlorination of the aromatic moiety, whose biochemical and genetic basis was not known previously. This first study on basidiomycete halogenases presents the biochemical in vitro characterization of five flavin-dependent species A. mellea enzymes (ArmH1 to ArmH5) that were heterologously produced in species Escherichia coli. We demonstrate that all five enzymes transfer a single chlorine atom to the melleolide backbone. A 5-fold, secured biosynthetic step during natural product assembly is unprecedented. Typically, flavin-dependent halogenases are categorized into enzymes acting on free compounds as opposed to those requiring a carrier-protein-bound acceptor substrate. The enzymes characterized in this study clearly turned over free substrates. Phylogenetic clades of halogenases suggest that all fungal enzymes share an ancestor and reflect a clear divergence between ascomycetes and basidiomycetes.
Melleolide, a new antibiotic from Armillaria mellea
Melleolide, a new sesquiterpenoid orsellinate, has been isolated from cultures of . Its structures was elucidated by X-ray crystallography.
Armillaric Acid, A New Antibiotic Produced by Armillaria mellea
A new antibiotic armillaric acid (2), has been isolated from the cultured mycelia of Armillaria mella (Vahl. ex Fr.) Quel (Trichlometaceae). Its structure was elucidated on the basis of the spectral data. Compound 2 exhibits inhibitory activity against gram-positive bacteria and yeast.
The cultivation, bioactive components and pharmacological effects of Armillaria mellea
Armillaria mellea, a symbiotic fungus in the underground tubers of Chinese Medicinal orchid Gastrodia elata, is one of the main biological active components and pharmaceutical effects of its host gastrodia. The purpose of this review is to bring attention to the biological properties of this unique A. mellea Mushroom and its constituents, as well as to suggest the potential for the development of new drugs related to this fungus. It contains various known and untapped bioactive metabolites such as polysaccharides, sesquiterpene aryl esters, steroids and fibrinolytic enzymes. It could be exploited as an important source of new biological natural products with anticonvulsant, immunomodulatory and antimicrobial functions. The batch culture is preferred as an alternative means of getting bioactive components from Armellaria fermentation. Challenges in investigations on A. mellea include the optimization of culture parameters, the further elucidation of the molecular pharmacological mechanism and relationship between structure and function of their secondary metabolites.
The water-soluble polysaccharide (AMP), with a molecular mass of 7.8 × 103 Da as determined by high-performance size-exclusion chromatography (HPSEC), was obtained from the fruiting body of Armillaria mellea. Methylation, Smith degradation, acetolysis, 1H and 13C NMR spectroscopy and acid hydrolysis studies were conducted to elucidate its structure. The Results indicated that AMP consisted of a backbone composed of (1→6)-linked-α-d-glucopyranosyl, (1→2,6)-linked-α-d-glucopyranosyl and (1→6)-linked-α-d-galactopyranosyl residues in the ratio of 3:1:1, and terminated with one single terminal (1→)-β-d-glucopyranosyl at the O-2 position of (1→2,6)-linked-α-d-glucopyranosyl, on average, along the main chain. Preliminary tests in vitro showed that AMP has stimulating effects on murine lymphocyte proliferation induced by concanavalin A or lipopolysaccharide in a dose-dependent manner. It is a possible potential immunopotentiating agent for use in health-care food or medicine.
Auricularia auricula-judae (higher Basidiomycetes)
antidiabetic and antioxidant activities of Eight Medicinal Mushroom species from China
The objective of the current study was to verify antidiabetic effects of different types of Mushrooms as folk medicines in treating diabetes. The antidiabetic effects were evaluated by in vitro α-glycosidase and aldose reductase (AR) inhibitory assays and antioxidant activity assay. Ganoderma lucidum extract exhibited the best dose-dependent inhibitory activity against α-glycosidase with IC50 at 4.88 mg/mL, and also exhibited aldose reductase inhibitory potential with IC50 value of 9.87 mg/mL. Tremella fuciformis demonstrated the highest AR inhibitory activity (IC50=8.39 mg/mL). antioxidant activities of selected Mushrooms were evaluated based on the total phenolic content (TPC), total flavonoids content (TFC), and DPPH free radical scavenging activity. The result showed that G. lucidum contained the highest TPC (39.3 mg GAE/g sample extract), TFC (15.1 mg CE/g sample extract), and the strongest DPPH free radical scavenging activity (IC50=3.66 mg/mL) among the Mushroom samples.
Auricularia auricula-judae, a nutrient-rich Mushroom used in traditional medicine, is a macroFungi that exhibits various biological properties. In this study, we have reported on the mechanisms that promote the wound-healing effects of a water-soluble polysaccharide–rich extract obtained from A. auricula-judae (AAP). AAP contained high amounts of polysaccharides (349.83 ± 5.00 mg/g extract) with a molecular weight of 158 kDa. The main sugar composition of AAP includes mannose, galactose, and glucose. AAP displayed antioxidant activity in vitro and was able to abort UVB-induced intracellular ROS production in human fibroblasts in cellulo. AAP significantly promoted both fibroblast and keratinocyte proliferation, migration, and invasion, along with augmentation of the wound-healing process by increasing collagen synthesis and decreasing E-cadherin expression (All p < 0.05). Specifically, the AAP significantly accelerated the wound closure in a mice skin wound-healing model on day 9 (2.5%AAP, p = 0.031 vs. control) and day 12 (1% and 2.5%AAP with p = 0.009 and p < 0.001 vs. control, respectively). Overall, our Results indicate that the wound-healing activities of AAP can be applied in an AAP-based product for wound management.
In this study, crude polysaccharides of culinary–Medicinal Mushroom Auricularia auricular-judae were extracted by hot water extraction and alcohol precipitation, and their antimicrobial and antioxidant activities were investigated. An optimum extraction condition was obtained at a ratio of liquid to solid 70 mL/g, temperature 90°C, time 4 h and extraction number 4. Accordingly, the best yield of crude polysaccharides was 6.89% with 76.12% in purity. Some bacteria and Fungi were used for antimicrobial studies. It was found that crude A. auricula-judae had great antimicrobial activities against Escherichia coli and Staphylococcus aureus, but no activities on the others. The inhibitory diameters of antimicrobial zones for the two were 5.55 ± 0.182 and 9.84 ± 0.076 mm, respectively. Moreover, crude A. auricula-judae had significant antioxidant activities in scavenging free radicals, reducing power assays, and Fe2+ chelating ability assay. Results revealed that crude A. auricula-judae has a great potential as antimicrobial and antioxidant, and it can be a supplementary food for human health.
Obesity, a rapidly growing threat to human health worldwide, is responsible for a large proportion of the total burden of disease. Therefore, obesity control could be a vital scheme to prevent many diseases. The aim of this study was to examine the activities and mechanism of Auricularia auricula-judae 70% ethanol extract (AAE) in preventing hypolipidemic and hepatic steatosis. A normal diet (ND) and a high-fat diet (HFD) with or without 0.1% (w/w), 0.3% (w/w), and 1% (w/w) AAE were given to male C57BL/6 mice. plasma lipids and liver enzymes were measured and tissue sections of liver were examined. Further mechanistic studies of mouse 3T3-L1 adipocytes were performed in vitro by verifying triglyceride, glycerol, and glycerol-3-phosphate dehydrogenase activity and messenger RNA expression of adipogenic and lipogenic genes using reverse transcriptase polymerase chain reaction amplification. Body weight and adipose tissue mass were significantly reduced in mice fed an ND and a HFD plus AAE compared with mice fed an HFD. In AAE-supplemented groups, plasma lipids and liver enzymes decreased dose-dependently. AAE suppressed the expression of adipogenic/lipogenic genes (PPARγ, C/EBPα, FAS) in 3T3-L1 cells without cytotoxicity. These findings suggest that AAE may reduce the risk of hepatic steatosis by modulating plasma lipids via the regulation of adipogenic/lipogenic transcriptional factors. AAE may have interesting applications to improve plasma lipids and liver enzymes.
Auricularia auricula-judae is an important culinary–Medicinal Mushroom. The A. auricula-judae polysaccharides (AAPs) were prepared from A. auricula-judae in the early stage through alkali extraction and deproteination with the Sevag method, and optimal acid hydrolysis conditions were established by Box−Behnken to prepare the degraded polysaccharides (AAPs-F) from AAPs. In this study, a nonenzymatic glycosylation reaction system was used for the evaluation of the inhibitory effects on the formation of advanced glycation end products (AGEs). In addition, high glucose resistance was assessed by glucose consumption of HepG2 cells and the lifespan of Caenorhabditis elegans under high sugar stress. It was found that both 0.5 mg·mL-1 AAPs and 0.2 mg·mL-1 AAPs-F could significantly inhibit AGE formation in short- and long-term glycosylation (P < .05) in a dose-dependent manner, determined by ultraviolet and fluorospectrophotometry. It indicated activity against AGE formation for different concentrations of AAPs and AAPs-F. AAPs-F at 0.5 mg·mL-1 significantly enhanced the glucose absorption of HepG2 cells by 24.4% (P < .05) in a dose-dependent manner at 24 h, and markedly extended the lifespan of C. elegans by 32.9% (P < 0.05) under high sugar stress conditions. This study demonstrated that the derived hydrolysates produced by the hydrolysis of acid had a prominent effect on the inhibition of AGE formation and relieved the stress state caused by high sugar levels.
Auricularia polytricha
Auricularia polytricha was cultivated on a sawdust basal substrate supplemented with different proportions (30%, 45%, and 60%, respectively) of stalks of three grass plants, i.e., Panicum repens (PRS), Pennisetum purpureum (PPS), and Zea mays (ZMS), to determine the most effective substrate. The mycelial growth rate, total colonization time, days to primordial formation, biological efficiency and chemical composition of fruiting bodies were evaluated. The Results indicated that 30PPS was the best substrate for mycelial growth of A. polytricha, with a corresponding total colonization period of 32.0 days. With the exception of 30PPS, the total biological efficiency of all of the substrates containing P. repens stalk, P. purpureum stalk and Z. mays stalk was higher (P < 0.05) than that of the control. The most suitable substrate with a high biological efficiency was 60PRS (148.12%), followed by 30ZMS (145.05%), 45ZMS (144.15%) and 30PRS (136.68%). The nutrient values of fruiting bodies were affected by different substrates. The ash contents of A. polytricha cultivated on a substrate containing Z. mays stalk were higher than that of the control; meanwhile, the protein contents of Mushroom cultivated on a substrate containing P. repens stalk (except substrate 45PRS) were higher than that of the control. The biological efficiency of the substrates was tested, and according to the Results, it is feasible to use the stalks of P. repens and Z. mays on partially replaced sawdust to cultivate A. polytricha.
Boletus speciosus Frost
The fungal polysaccharides have been revealed to exhibit a variety of biological activities, including antitumor, immune‑stimulation and antioxidation activities. In the present study, the immune and anticancer activities of a novel polysaccharide, BSF‑A, isolated from Boletus speciosus Frost was investigated. The inhibitory rate of S180 tumors in mice treated with 40 mg/kg BSF‑A reached 62.449%, which was the highest rate from the three doses administered; this may be comparable to mannatide. The antitumor activity of BSF‑A is commonly considered to be a consequence of the stimulation of the cell‑mediated immune response, as it may significantly promote the macrophage cells in the dose range of 100‑400 µg/ml in vitro. The levels of the cytokines, IL‑6, IL‑1β and TNF‑α, and nitric oxide, induced by BSF‑A treatment at varying concentrations in the macrophage cells were similar to the levels in the cells treated with lipopolysaccharide. There was weak expression of the TNF‑α, IL‑6, IL‑1β and inducible nitric oxide synthase mRNA in the untreated macrophages, but this increased significantly in a dose‑dependent manner in the BSF‑A‑treated cells. BSF‑A also had a time‑ and dose‑dependent effect on the growth inhibition of the Hep‑2 cells, with the concentration of 400 µg/ml having the highest inhibitory rate. A quantitative PCR array analysis of the gene expression profiles indicated that BSF‑A had anticancer activities that affected cell apoptosis in the Hep‑2 cells. The Results obtained in the present study indicated that the purified polysaccharide of Boletus speciosus Frost is a potential source of natural anticancer substances.
Conclusion: An analysis of transcriptome resources enabled us to examine gene expression profiles, verify differential gene expression, and select candidate signaling pathways as the mechanisms of the immunomodulatory activity of BSF-1. Based on the experimental data, we believe that the significant antitumor activities of BSF-1 in vivo mainly involve the MAPK signaling pathways.
A new water-soluble heteropolysaccharide with a molecular weight of 15 kDa was isolated from the fruiting bodies of Boletus reticulatus Schaeff. Structural characterization Results revealed that B. reticulatus Schaeff polysaccharide (BRS-X) had a backbone of 1,6-linked α-D-galactose and 1,2,6-linked α-D-galactose which branches were mainly composed of a terminal 4-linked β-D-glucose and the ratio of D-galactose and D-glucose was 5:1. Bioactivity assays indicated that BRS-X displayed a strong proliferative activity in T cells and B cells and promoted the secretion of immunoglobulin G (IgG), IgE, IgD and IgM. In addition, BRS-X could facilitate the proliferation and phagocytosis of RAW264.7 cells and could significantly inhibit the growth of tumors in S180-bearing mice. The Results of transcriptome sequencing analysis illustrated that total 46 genes enriched in MAPK and total 34 genes enriched in PI3K/Akt signaling pathways in BRS-X group. The protein VEGF and VEGFR expression were significantly reduced under the treatment with BRS-X. These findings provide a scientific basis for the edible and Medicinal value of BRS-X.
A homogeneous water-soluble flaky polysaccharide named LRP-1 (18.82 kDa) was extracted and purified from the rare edible and Medicinal Fungi Leccinum rugosiceps. The structure characterization of LRP-1 was analyzed by GPC, GC, GC–MS, FT-IR, SEM, 1D/2D NMR, and its antitumor and immunoregulatory activities were determined. The Results show that LRP-1 is a new polysaccharide with a backbone which is mainly composed of →1-α-D-Fucp-3→, →1-α-D-Rhap-3→, →1-β-D-Glcp-6→, →1-β-D-Glcp-3→, →1-α-D-Glcp-4→, →1-β-D-Galp-6 → and →1-α-D-Manp-6→. Results of MTT assay show that LRP-1 inhibit the growth of human hepatoma cells HepG-2 and human breast carcinoma MCF-7 cells in vitro. LRP-1 could also induce the secretion of NO and immune factors (IL-6 and TNF-α) of RAW264.7. This study suggests that LRP-1 has potential to be used as nutraceutical food with antitumor and immunoregulatory activities.
polysaccharides in boletes (Boletales) are economically significant to both function food and Medicinal industries. The polysaccharides were extracted from the fruit bodies of eight boletes, namely, Aureoboletus longicollis, Butyriboletus hainanensis, Crocinoboletus rufoaureus, Hemioporus japonicus, Neoboletus infuscatus, Neoboletus obscureumbrinus, Tylopilus otsuensis, Xanthoconium fusciceps, which were collected from tropical China; their physicochemical properties and antioxidant activities were characterised and evaluated, respectively. The Results revealed that the polysaccharides among the eight boletes were mainly composed of glucose, mannose, and galactose, with a broad molecular weight range, and contained a pyranose ring revealed by FT-IR and NMR spectral analyses. Many factors such as different species of boletes, geographic conditions, molecular weight, configuration, and monosaccharide content may affect the antioxidant power of polysaccharides, simultaneously, instead of one single factor. The antioxidant activities of the polysaccharides were measured according to in vitro assays of DPPH scavenging, superoxide anion scavenging, and ferrous ion reducing tests. The polysaccharide of C. rufoaureus has greatly superior antioxidant activity and it could serve as potential functional food or medicine.
Unlike many saprobic edible Mushrooms, few of the edible mycorrhizal Mushrooms can be cultivated. The market is supplied with what can be collected in the Northern Hemisphere during the few months of the year that each species fruits. Most do not preserve well and few have made the accidental journey from the Northern to the Southern Hemisphere. There is, therefore, a golden opportunity for the production of these high value foods in the Southern Hemisphere for Northern Hemisphere off-season markets. Boletus edulis (porcini) has become naturalised in South Africa, Kenya and New Zealand while Lactarius deliciosus (saffron milk cap) is well established in Australia and both Tuber borchii (bianchetto) and Rhizopogon rubescens (shoro) in New Zealand. It has also been demonstrated that commercial quantities of Tuber melanosporum (Périgord black truffle) can be produced in New Zealand and that fruiting bodies of both saffron milk cap and shoro will fruit in experimental plantations. This provides a sound basis for further research aimed at the commercial production of important edible ectomycorrhizal Mushrooms in Southern Hemisphere countries primarily aimed at off-season Northern Hemisphere markets.
anticancer and other therapeutic relevance of Mushroom polysaccharides: A holistic appraisal
The discovery of nutritious dietary supplements and side effect-free therapeutics are a priority in the current scenario of increasing instances of metabolic syndromes. In this direction, Mushroom polysaccharides have shown immense promise. Scores of studies have characterized and evaluated their biological relevance, which range from antioxidant, anti-inflammatory, anticancer, antidiabetic, antimicrobial, and antilipemic to immunomodulatory. Hence, it is important to accumulate the key findings of these investigations, and to apply the insights to develop functional foods, and immunomodulators. This review attempts to meet this goal by gleaning the key discoveries on Mushroom polysaccharides in the recent years, and to present them in a comprehensive manner. With this objective, the physiological relevance of the polysaccharides, the underlying mechanism, and hurdles in the path of their therapeutics transition, have been discussed. Finally, critical comments have been made to expedite research in this area.
A new anti-tumor protein (designated as Boletus edulis or in short BEAP) was isolated from dried fruit bodies of the edible bolete Mushroom Boletus edulis. The purification protocol employed comprised fast ion exchange chromatography on a Hitrap Q column and ion exchange chromatography on a DEAE-52 cellulose column. Superdex G75 gel filtration and SDS-PAGE analysis revealed that BEAP was a protein with a molecular weight of 16.7 KD. The protein exhibited potent anti-cancer activity on A549 cells both in vitro and in vivo. With the use of AO/EB staining, annexin V-FITC/PI, and Western blotting, it was demonstrated in vitro that the cytotoxicity of BEAP was mediated by induction of apoptosis and arrest of A549 cells in the G1 phase of the cell cycle. BEAP significantly suppressed the growth of A549 solid tumors in vivo. These Results prove that BEAP is a new multifunctional protein with anti-tumor and anti-metastasis capabilities.
Cantharellus cibarius
CANTHARELLUS CIBARIUS ñ culinary–Medicinal Mushroom
CONTENT AND BIOLOGICAL activity
One of the most frequently harvested Mushrooms in Polish forests is Yellow chanterelle (chanterelle) ñ Cantharellus cibarius Fr. from the Cantharellaceae family. Chanterelle is an ectomycorrhizal Mushroom occurring in Poland. Chanterelle lives in symbiosis with pine, spruce, oak and hornbeam. In cookery, chanterelle is appreciated because of the aroma, taste, firmness and crunchiness of its fruiting bodies. wild edi-ble Mushrooms are widely consumed in Asia, Western Europe and Central America. Chanterelle contains agreat number of carbohydrates and proteins and a low amount of fat. Actual review presents the main groupsof physiologically active primary and secondary metabolites in the fruiting bodies of chanterelle such as indole and phenolic compounds, carbohydrates, fatty acids, proteins, free amino acids, sterols, carotenoids, enzymes,vitamins and elements with biological activity. The presence of these compounds and elements conditions thenutrient and therapeutic activity of chanterelle, e.g., immunomodulatory, anti-inflammatory, antioxidant, antivi-ral, antimicrobial and antigenotoxic properties.
Ceriporia lacerata
skincare is very critical in preventing aging and skin trouble, which is difficult to recover if progressed. However, the development of effective anti-aging solutions is still on the horizon. The purpose of this study was to evaluate the functional efficacy of Ceriporia lacerata exo-pharmaceutical substance (CLEPS) in view of its use in innovative skin care cosmetics. CLEPS was found to have no cytotoxicity against normal human dermal fibroblasts and B16 melanoma cells in a wide concentration range of 0.05–7 mg/mL. It exhibited a whitening effect by inhibiting melanin synthesis comparable to that of the respective reference compound (arbutin). Notably, CLEPS not only substantially increased collagen (65.4%) and filaggrin synthesis (36%), but also significantly inhibited the activity of collagenase (93.4%), suggesting that CLEPS could prevent skin barrier damage or skin wrinkles. In addition, it showed an excellent anti-inflammatory effect and wound-healing effect. Overall, CLEPS exhibited exceptional anti-aging effects in human skin cells, designating as a potential natural cosmeceutical ingredient.
Chroogomphidius viscidus
species Diversity and Utilization of Medicinal Mushrooms and Fungi in China
The investigation and utilization of Medicinal Fungi in China has received considerable attention in recent years. However, information on Medicinal Fungi is scattered throughout the literature, and many nomenclatural inconsistencies have been found in the Chinese reports. The publications on Chinese Medicinal Fungi have been critically checked; as a result, 540 Medicinal Mushrooms and Fungi from China were enumerated in the present checklist. All names have been checked or revised in accordance with contemporary taxonomy and the latest version of the International Code of Botanical Nomenclature (Vienna Code). The “out-of-date” names, illegitimate names, nonexistent names, and misapplied names in previous reports were revised. The common synonyms are listed after their valid names. The main Medicinal functions of each species, together with the original or important references, are provided. The 540 species belonging to 10 classes, 26 orders, 76 families, and 199 genera of Ascomycota and Basidiomycota have been recorded with Medicinal values. Most are the higher Basidiomycetes (482 species), which comprise approximately 89% of all the Chinese Medicinal species. In total, 126 Medicinal functions are thought to be provided by Chinese Medicinal Fungi, and 331 (61% of the total Medicinal Fungi) can be used as antitumor agents. Other common functions are hemostasis, antibacterial, improving immunity, detoxication, and anti-inflammatory. Fifteen species, including Ganoderma lucidum, are the most important or commonly used Medicinal Fungi, and 26 species, including Agaricus bisporus, are commonly cultivated in China as food or for Medicinal products.
We investigated a total of 335 samples of Korean native Mushroom extracts as part of our lipoxygenase (LOX) inhibitor screening program. Among the Mushroom-methanolic extracts we investigated, 35 exhibited an inhibitory activity greater than 30% against LOX at a concentration of 100 μg/mL. Especially, Collybia maculata, Tylopilus neofelleus, Strobilomyces confusus, Phellinus gilvus, P. linteus, P. baumii, and Inonotus mikadoi exhibited relatively potent LOX inhibitory activities of 73.3%, 51.6%, 52.4%, 66.7%, 59.5%, 100.0%, and 85.2%, respectively. Bioassay-guided fractionation led to the isolation of inoscavin A from the methanolic extract of P. baumii, which showed the most potent activity and was identified by spectroscopic methods. Specifically, inoscavin A exhibited potent LOX inhibitory activity with an IC50 value of 6.8 μM.
antibacterial activity in Higher Fungi (Mushrooms) and Endophytic Fungi from Slovenia
Discovery and development of new antibiotics is still very important because of the constant appearance of drug-resistant pathogenic bacteria. The broth microdilution test was applied for screening of antibacterial activity in extracts of higher and endophytic Fungi. Among tested extracts, three possessed significant antibacterial activity: extracts of Mushrooms Amanita virosa. (Fr.) Bertill. (Amanitaceae) and Cortinarius praestans. Cordier (Cortinariaceae) against Pseudomonas aeruginosa. and Staphylococcus aureus., respectively, and extract of endophytic fungus Trucatella hartigii. (Tubeuf) Steyaert (Amphisphaeriaceae) against Enterococcus faecalis. and S. aureus.. The extract of Truncatella hartigii. was further analyzed by one- and two-dimensional thin-layer chromatography, and the position of the active compound was determined on the chromatogram.
antimicrobials from Mushrooms for Assuring Food Safety
The interest in discovering and developing natural antimicrobials has significantly increased due to consumer preferences for foods that are free of chemical preservatives while still microbiologically safe. One of the best sources of natural antimicrobials is certain Mushrooms (Fungi) as many of them not only have nutraceutical functions but also possess antimicrobial properties. This article reviews the available information on Mushroom antimicrobials for food safety control. It includes available resources, extraction procedures, antimicrobial activities, and the status of their applications to food safety. The review indicates that there are great potential benefits to be gained from Mushroom antimicrobials in food production, processing, and preservation as a biosolution to meet the increasing demands for food quality and safety.
In the present study, we assembled and annotated the complete mitochondrial genome of Chroogomphus rutilus. The complete mitochondrial genome of C. rutilus was composed of circular DNA molecules, with a size of 37,508 bp. The GC content of the C. rutilus mitogenome was 22.82%. A total of 18 protein-coding genes (PCGs), 2 ribosomal RNA (rRNA) genes, and 24 transfer RNA (tRNA) genes were detected in the C. rutilus mitogenome. Phylogenetic analysis based on combined mitochondrial gene dataset indicated that the C. rutilus exhibited a close relationship with species from the genus Rhizopogon. This study served as the first report on the complete mitochondrial genome from the family Gomphidiaceae, which will promote the understanding of phylogeny, evolution, and taxonomy of this important fungal species.
In vivo and in vitro treatments were carried out to investigate the effects of a 95% ethanol extract of Chroogomphus rutilus (CRE) on antioxidant, hypoglycemic, hypolipidemic, and antitumor properties. CRE showed potent radical scavenging activity against DPPH in vitro. It could increase antioxidant enzymatic activities (superoxide dismutase and glutathione peroxidase) and could reduce malondialdehyde content in vivo in mice in which aging was induced by D-galactose. CRE had hypoglycemic activity and could significantly inhibit α-glucosidase activity in vitro and decrease blood glucose concentration in vivo. CRE could decrease the serum total cholesterol, triglyceride, and low-density lipoprotein cholesterol levels and increase the high-density lipoprotein cholesterol level in diabetic mice. The MTT assay showed that CRE also had a certain inhibitory effect on the tumor cells. These Results suggest that CRE may be beneficial for human health and could be useful for applications in medicine, the food industry, and agriculture.
Clitocybe aurantiaca
A New antioxidant, Clitocybin A, from the Culture Broth of Clitocybe aurantiaca
Clitocybin A (1), a new antioxidant, was isolated from the culture broth of Clitocybe aurantiaca. This compound was purified by solvent extraction, silica gel column chromatography, Sephadex LH-20 column chromatography and preparative HPLC. Its structure was determined as 4,6-dihydroxy-2-ρ-hydroxyphenyl-isoindol-1-one on the basis of the UV, NMR, and MS spectroscopic analysis. The compound 1 showed potent free radical scavenging activity against superoxide, ABTS, and DPPH radicals, and protective effect against cellular DNA damage induced by oxidative stress.
Clitocybin D, a novel human neutrophil elastase inhibitor, was isolated from the culture broth of Clitocybe aurantiaca. This compound was purified by solvent extraction, silica gel column chromatography, Sephadex LH-20 column chromatography, and preparative HPLC. The compound was determined to be 4-(4,6-dihydroxy-3-methoxy-3H-isoindol-1-yl)-benzoic acid on the basis of 1D and 2D NMRs and MS spectroscopic analysis. Analysis of the human neutrophil elastase (HNE) inhibitory activity of the isolated compound revealed that it showed significant HNE inhibitory activity with an value of .
High concentration of intracellular reactive oxygen species (ROS) plays a role in damaging biological systems. We isolated clitocybin A from the culture broth of Clitocybe aurantiaca and then clitocybin B and C derivatives were synthesized from clitocybin A. IMR-90 lung fibroblast cells were pre-treated or post-treated with clitocybin A, B and C to the addition of 100 μM H2O2. These compounds inhibited the level of intracellular reactive oxygen species (ROS) and H2O2-induced cell death as judged by hypodiploid cell formation. The inhibitory effect of clitocybins on H2O2-induced cell death was comparable to that with N-acetylcysteine (NAC), a well-known ROS scavenger. The inhibition of H2O2-induced cell death by clitocybins was mediated by the reduction of caspase 3 and 9 activation, cytochrome c release from mitochondria and the degradation of IκB-α and IκB-β, which could be resulted in the prevention of cellular senescence. It suggests that clitocybins are novel compounds scavenging ROS and protect cells from apoptosis and cellular senescence.
Abnormal proliferation of vascular smooth muscle cells (VSMCs) plays an essential role in the pathogenesis of vascular diseases, such as atherosclerosis, hypertension, and restenosis. Clitocybin A, a novel isoindolinone, isolated from the culture broth of Mushroom Clitocybe aurantiaca has been reported to possess free radical scavenging activity. However, the antiproliferative effects of clitocybin A on VSMCs are unknown. In the present study, we investigated the effect of clitocybin A on platelet-derived growth factor (PDGF)-BB–induced proliferation of VSMCs and examined the molecular basis of the underlying mechanism. Clitocybin A inhibited DNA synthesis and cell proliferation. In accordance with These findings, clitocybin A blocked the PDGF-BB–inducible progression through G0/G1 to S phase of the cell cycle in synchronized cells and decreased the expression of cyclin-dependent kinase (CDK) 2, CDK4, cyclin D1, cyclin E, and proliferative cell nuclear antigen. In addition, clitocybin A inhibited the PDGF-BB–induced phosphorylation of phosphatidylinositol 3 kinase (PI3K) / Akt kinase. However, clitocybin A did not change the expression levels of extracellular signal-related kinase (ERK) 1/2, phospholipase C-γ1, and PDGF-Rβ phosphorylation. These Results indicate that clitocybin A may inhibit VSMCs proliferation through G1 phase arrest by regulating the PI3K/Akt pathway.
Clitocybin A, an isoindolinone from Clitocybe aurantiaca, was investigated to assess its anti-wrinkle properties, through reactive oxygen species (ROS)-scavenging and elastase inhibitory activities, procollagen synthesis, and matrix metalloproteinase-1 (MMP-1) expression, in human primary dermal fibroblast-neonatal (HDF-N) cells. Clitocybin A exhibited no significant cytotoxicity up to 10 ppm in HDF-N cells, with cell viability and cell proliferation activity greater than 94.6% and 91.9%, respectively. Strong and concentration-dependent ROS radical scavenging activities of clitocybin A were observed following irradiation with UVB at . Furthermore, clitocybin A treatment of cells at 0.1, 1, and 10 ppm exhibited decreased elastase activity, in a concentration-dependent manner, by 1.97%, 6.6%, and 8.31%, respectively, versus the control group. The effects of clitocybin A on procollagen synthesis and MMP-1 expression were investigated. Clitocybin A treatment of cells at 1, 5, and 10 ppm increased procollagen synthesis, by 67.9%, 74.4%, and 112.9%, respectively, versus the control group. At these concentrations, MMP-1 expression decreased significantly following UV irradiation. Together, These findings suggest that clitocybin A may be an effective ingredient for use in anti-wrinkle cosmetic products.
Clitocybin A is a novel anti-wrinkle cosmetic agent produced by the strain from a Korean native Mushroom Clitocybe aurantiaca. In this study, fermentation, extraction, and purification conditions for a large scale production of clitocybin A were optimized, and its cytotoxicity and inhibition activity on the expression of matrix metalloproteinase-1 (MMP-1) were characterized. The mass production of anti-wrinkle agent was achieved according to the 300 L fermentation process with a fed-batch cultivation using the modified yeast-maltose (YM) broth, and a total of 12.5 kg of cell mass was obtained in a 120 L culture broth for 14 days. After extraction and purification, clitocybin A was identified by HPLC. The cytotoxicity of clitocybin A was examined by the MTT assay. When assayed at 100 and 200 concentrations, clitocybin A showed no cytotoxicity, demonstrating safety. The inhibition activity of clitocybin A on the expression of MMP-1 was examined against UV irradiation. Oleanolic acid (control group) showed a relatively low MMP-1 inhibiting activity (ca. 16.7%) at 10 and showed increased cytotoxicity at higher concentrations. In contrast, clitocybin A showed no cytotoxicity at 100 , and exhibited a relatively high MMP-1-inhibiting activity (33.1%). These findings indicate that clitocybin A may be a safe and effective anti-wrinkle agent for use in functional cosmetics.
High concentration of intracellular reactive oxygen species (ROS) plays a role in damaging biological systems. We isolated clitocybin A from the culture broth of Clitocybe aurantiaca and then clitocybin B and C derivatives were synthesized from clitocybin A. IMR-90 lung fibroblast cells were pre-treated or post-treated with clitocybin A, B and C to the addition of 100 μM H2O2. These compounds inhibited the level of intracellular reactive oxygen species (ROS) and H2O2-induced cell death as judged by hypodiploid cell formation. The inhibitory effect of clitocybins on H2O2-induced cell death was comparable to that with N-acetylcysteine (NAC), a well-known ROS scavenger. The inhibition of H2O2-induced cell death by clitocybins was mediated by the reduction of caspase 3 and 9 activation, cytochrome c release from mitochondria and the degradation of IκB-α and IκB-β, which could be resulted in the prevention of cellular senescence. It suggests that clitocybins are novel compounds scavenging ROS and protect cells from apoptosis and cellular senescence.
Clitocybin A, an isoindolinone from Clitocybe aurantiaca, was investigated to assess its anti-wrinkle properties, through reactive oxygen species (ROS)-scavenging and elastase inhibitory activities, procollagen synthesis, and matrix metalloproteinase-1 (MMP-1) expression, in human primary dermal fibroblast-neonatal (HDF-N) cells. Clitocybin A exhibited no significant cytotoxicity up to 10 ppm in HDF-N cells, with cell viability and cell proliferation activity greater than 94.6% and 91.9%, respectively. Strong and concentration-dependent ROS radical scavenging activities of clitocybin A were observed following irradiation with UVB at . Furthermore, clitocybin A treatment of cells at 0.1, 1, and 10 ppm exhibited decreased elastase activity, in a concentration-dependent manner, by 1.97%, 6.6%, and 8.31%, respectively, versus the control group. The effects of clitocybin A on procollagen synthesis and MMP-1 expression were investigated. Clitocybin A treatment of cells at 1, 5, and 10 ppm increased procollagen synthesis, by 67.9%, 74.4%, and 112.9%, respectively, versus the control group. At these concentrations, MMP-1 expression decreased significantly following UV irradiation. Together, These findings suggest that clitocybin A may be an effective ingredient for use in anti-wrinkle cosmetic products.
Clitocybin A is a novel anti-wrinkle cosmetic agent produced by the strain from a Korean native Mushroom Clitocybe aurantiaca. In this study, fermentation, extraction, and purification conditions for a large scale production of clitocybin A were optimized, and its cytotoxicity and inhibition activity on the expression of matrix metalloproteinase-1 (MMP-1) were characterized. The mass production of anti-wrinkle agent was achieved according to the 300 L fermentation process with a fed-batch cultivation using the modified yeast-maltose (YM) broth, and a total of 12.5 kg of cell mass was obtained in a 120 L culture broth for 14 days. After extraction and purification, clitocybin A was identified by HPLC. The cytotoxicity of clitocybin A was examined by the MTT assay. When assayed at 100 and 200 concentrations, clitocybin A showed no cytotoxicity, demonstrating safety. The inhibition activity of clitocybin A on the expression of MMP-1 was examined against UV irradiation. Oleanolic acid (control group) showed a relatively low MMP-1 inhibiting activity (ca. 16.7%) at 10 and showed increased cytotoxicity at higher concentrations. In contrast, clitocybin A showed no cytotoxicity at 100 , and exhibited a relatively high MMP-1-inhibiting activity (33.1%). These findings indicate that clitocybin A may be a safe and effective anti-wrinkle agent for use in functional cosmetics.
A New antioxidant, Clitocybin A, from the Culture Broth of Clitocybe aurantiaca
Clitocybin A (1), a new antioxidant, was isolated from the culture broth of Clitocybe aurantiaca. This compound was purified by solvent extraction, silica gel column chromatography, Sephadex LH-20 column chromatography and preparative HPLC. Its structure was determined as 4,6-dihydroxy-2-ρ-hydroxyphenyl-isoindol-1-one on the basis of the UV, NMR, and MS spectroscopic analysis. The compound 1 showed potent free radical scavenging activity against superoxide, ABTS, and DPPH radicals, and protective effect against cellular DNA damage induced by oxidative stress.
Medicinal macroFungi as cosmeceuticals: A Review
Macro Fungi (Mushrooms) have been studied for their nutritional value and Medicinal properties. However, progress in the biotechnological application of macroFungi in the cosmetic industry as cosmeceuticals and nutricosmetics remains slow. Currently, the cosmetic industry is in a constant search for valuable natural ingredients or extracts with relevant bioactive properties (e.g., antiaging, anticollagenase, antielastase, antihyaluronidase, antipigmentation, anti-inflammatory, antioxidant, and antityrosinase) to design formulations. edible Medicinal Mushrooms are an unlimited source of nutraceuticals and pharmaceuticals. They can be used as a source of ingredients to develop organic cosmeceuticals, nutriceuticals, and nutracosmetics for topical and oral administration.
Synthesis of Clitocybin A, B and C and their Biological Evaluation for antioxidant activities
Clitocybin A, isolated from the culture broth of Mushroom Clitocybe aurantiaca, showed various biological activities such as cell death inhibition effects, anti-wrinkle effects, aortic smooth muscle cell proliferation inhibition effects. In an effort to further develop this promising compound toward a potent antioxidant, we have modified the structure of clitocybin A by changing the number of free phenolic hydrogen in isoindolinone moiety. In this paper, clitocybin A and its analogues, clitocybin B and C were synthesized and their antioxidant activities were evaluated. Clitocybin A possessing two phenolic hydrogens in isoindolinone moiety of clitocybin A analogues showed more potent radical scavenging activity than clitocybin B possessing one phenolic hydrogen. In inhibition of cellular DNA damage in H2O2treated cells, clitocybin C lacking free phenolic hydrogen in isoindolinone moiety showed more potent activity than clitocybin A possessing two phenolic hydrogens.Among the tested compounds, clitocybin A only showed dose-dependently HNE inhibitory activity with an IC50 value of 78.8 uM. The presence of free phenolic hydrogens inisoindolinone moiety of clitocybin A analogues plays an important role in antioxidant activities.
inhibitory effect of Melanogenesis by 5-Pentyl-2-Furaldehyde Isolated from Clitocybe sp.
In the continued search for melanogenesis inhibitors from microbial metabolites, we found that the culture broth of Clitocybe sp. MKACC 53267 inhibited melanogenesis in B16F10 melanoma cells. The active component was purified by solvent extraction, silica gel chromatography, Sephadex LH-20 column chromatography, and finally by preparative HPLC. Its structure was determined as 5-pentyl-2-furaldehyde on the basis of the UV, NMR, and MS spectroscopic analysis. The 5-pentyl-2-furaldehyde potently inhibited melanogenesis in B16F10 cells with an value of 8.4 , without cytotoxicity.
Clitocybe geotropa
Agaricomycetes Mushrooms (Basidiomycota) as potential neuroprotectants
Badalyan S.M. et Rapior S. Agaricomycetes Mushrooms (Basidiomycota) as potential neuroprotectants. Italian Journal of Mycology, 50, 30-43 (2021). doi:10.6092/issn.2531-7342/12542 _______ The edible and Medicinal agaricoid and polyporoid Mushrooms (phylum Basidiomycota, order Agaricomycetes) have long been known by humans as valuable food and medicines. They are producers of different groups of high- and lowmolecular weight bioactive compounds (alkaloids, phenolics, polysaccharides, proteins, terpenoids, vitamins etc.) with around 130 therapeutic effects, including neuroprotective. Mushroom-derived biotech products are reported as effective neuroprotectants, however their potential to prevent or mitigate several neurodegenerative pathologies, such as Alzheimer and Parkinson diseases, epilepsy, depression and others has not been fully explored. This review discusses the neuroprotective potential of Agaricomycetes Fungi and possibilities for their application as natural neuroprotectants.
Clitocybe gibba (Fr.) Kummer
Infundibulicybe geotropa (Bull.) Harmaja is an edible mushroom found in Bolu province in northwestern Turkey. The chemical composition and bioactivity of these mushrooms has not been previously investigated. We examined the phenolic composition, elemental content, and antioxidant and antigenotoxic effects of methanol extracts of fruiting bodies. The phenolic compounds in the fungal samples were determined using high-performance liquid chromatography (HPLC), and element content was determined using atomic absorption spectrophotometry. Total antioxidant status (TAS), total oxidant status (TOS), and oxidative stress index (OSI) were determined using the commercially available Rel assay kit. The antigenotoxic effects of the extract were determined using the MTT assay to assess cell viability and the alkaline single-cell gel electrophoresis assay (Comet assay). The total phenolic content (ppm) of I. geotropa was found to be catechin (), clorogenic acid (), and coumaric acid (). The TAS, TOS, and OSI of the extract were mmol/L, μmol/L, and , respectively. The elemental levels were within “normal” range. In HT22 mouse hippocampal neuronal cells, the extract (100 and 200 μg/ml) showed no genotoxic potential and ameliorated hydrogen peroxide- (H2O2-) induced oxidative DNA damage. I. geotropa may be considered a good nutrient due to its phenolic constituents and antioxidant potential.
Clitocybe Nebularis
Current knowledge of the Medicinal properties of Basidiomycetes Mushroom species of the genus Clitocybe and of the biological activity of C. nebularis fruiting bodies is reviewed. The main focus is the therapeutic potential of lectins from C. nebularis. species of the genus Clitocybe, including C. nebularis, have not been traditionally considered as Medicinal Mushrooms; however, recent studies have demonstrated their antitumor, immunomodulatory, and antioxidative properties, their antimicrobial (antiviral, antibacterial, and antifungal) activities against various bacteria and Fungi, as well as their potential use in therapy for alcoholism and as psychotropic agents. These activities have been shown to be due to various compounds, either isolated or in extracts, mainly polysaccharides but also phenols, ribonucleosides, and proteins. These include laccase, protease inhibitors, and lectins. C. nebularis has been shown to be rich in a variety of lectins and isolectins with distinct carbohydrate-binding specificities, showing versatile biological activities. They exhibit immunostimulatory and adhesion-/phagocytosis-promoting properties, as well as toxicity in various invertebrates. Mushroom species of the genus Clitocybe, including C. nebularis, thus constitute a valuable source of compounds showing diverse biological activities with a broad potential for applications in biomedicine or biotechnology. On the basis of such evidence reviewed here, we propose that C. nebularis and other Clitocybe species can be considered to be Medicinal Mushrooms.
Coprinus comatus (Agaricomycetes)
Coprinus comatus, an edible and Medicinal Mushroom, not only tastes delicious, but also has various pharmacological activities. Recently, it has been reported that researchers have extracted more and more active ingredients, including polysaccharides, comatin, active protein complexes, and phenols from fruit bodies, mycelium, or fermentation liquor of C. comatus and studied their corresponding functions. At present, researchers mainly focus on the hypoglycemic effect of C. comatus, while other effects are less studied. This paper summarizes not only the hypoglycemic effect of C. comatus, but also other functions, such as antioxidant activity, alcohol liver protection, cancer inhibition, antiandrogenic function, anti-inflammatory effect, treatment of leukemia, and so on, which will provide scientific basis for the deep processing and comprehensive utilization of C. comatus.
The culinary–Medicinal Mushroom Coprinus
comatus as a natural Antiandrogenic
Modulator
Prostate cancer is the most common cancer diagnosed in men. chemotherapy, androgen ablation, and androgen antagonist treatments have proven to have significant effects in the early stages of prostate cancer, whereas advanced prostate cancer is resilient to such treatments. The androgen receptor (AR), a ligand-dependent transcription factor, is the major drug target of prostate cancer therapy. Transition to the androgen-independent stage involves the activation of signaling pathways, AR gene mutations, and other mechanisms. Higher basidiomycetes Mushrooms have been used since ancient times in folk medicine to treat a diversity of diseases, including cancer. The present study evaluates the antiandrogenic activity of different Coprinus comatus strains in their ability to interfere with AR function. The authors found that the most active extract was C comatus strain 734 extracted with hexane (CC734-H). This extract was able to (1) inhibit AR-mediated reporter activity, (2) inhibit the proliferation and viability of the LNCaP cell line, and (3) inhibit the colony formation of the LNCaP cell line, in comparison to the DU-145, PC-3, and MDA-Kb2 cells. In addition, CC734-H was able to reduce AR levels and prostate-specific antigen gene expression in the LNCaP-treated cell line. This study illustrates the potential of the C comatus Mushroom as a natural antiandrogenic modulator that could serve in the treatment of prostatic diseases
Three polysaccharide fractions from fruiting bodies of Coprinus comatus-CC30, CC60, and CC80-are obtained by water extraction and ethanol precipitation with ethanol percentages of 30%, 60%, and 80%, respectively. The hypoglycemic activity of the three fractions was tested based on mice with alloxan-induced diabetes. Results indicate that fraction CC60 is the most effective fraction in water extract from C. comatus; it can remarkably reduce the blood glucose concentration in 120 min at a dosage of 1000 mg/kg administered orally. It also presents a long-term hypoglycemic effect during 21 days of injection at the same dosage. This polysaccharide fraction provide a novel path to improve the treatment currently used for patients with diabetes. The data on mice spleen lymphocyte proliferation and protein tyrosine phosphatase 1B (PTP1B)-inhibiting activity of fractions indicate that the hypoglycemic activity of CC60 is possibly activated through immune stimulation, not PTP1B inhibition.shroom.
Cordyceps militaris
Cordyceps militaris (L.: Fr.) Link – An important Medicinal Mushroom.
Cordyceps militaris is an important Medicinal Mushroom useful for the extraction of several bio–metabolites for natural drugs to revitalize the various physiological systems of the body from the ancient era. The constituents of C. militaris are now using widely in the modern pharmaceutical industries. The active principles of C. militaris are beneficial to act principally as pro–sexual, anti– cancer, immunomodulatory, and anti–oxidant agent, let alone its others beneficial activities for most of the systems of the body. In addition, it has lots of clinical applications. The prospects of this novel Mushroom could be used not only for modern Medicinal manufacturers, but also for the community people for the betterment of their health
effects of various carbon sources and carbon/nitrogen ratios on production of a useful bioactive metabolite, cordycepin (3′-deoxyadenosine), by submerged cultivation of a Chinese traditional Medicinal Mushroom Cordyceps militaris were investigated in shake flasks. The carbon sources examined were lactose, sucrose, glucose, fructose, galactose, maltose and xylose, and glucose was found to be most favourable to cordycepin production, whereas cells grew best in galactose medium. The dry cell weight (DW) was increased with an increase in initial glucose concentration within the range of 25–70 g/l as investigated. The highest cordycepin production, i.e. 245.7 ± 4.4 mg/l on day 18, was obtained in medium containing 40 g glucose/l. To enhance further the cordycepin production, the effect of carbon/nitrogen ratios was studied using central composite design and response surface analysis. The maximum cordycepin production and productivity of 345.4 ± 8.5 mg/l and 19.2 ± 0.5 mg/l per day were achieved in medium with optimized carbon and nitrogen sources, i.e. 42.0 g glucose/l and 15.8 g peptone/l. The information obtained is helpful for the hyperproduction of cordycepin by submerged cultivation of C. militaris on a large scale.
production of cordycepin by surface culture using the Medicinal Mushroom Cordyceps militaris
The production conditions of cordycepin (3′-deoxyadenosine), which is a kind of nucleoside analogue, were investigated by a surface culture using Cordyceps militaris NBRC 9787. About 98% of the cordycepin synthesized by Cordyceps militaris was secreted into the culture medium, and other nucleic acid-related compounds except for cordycepin and guanine were only slightly observed in the medium. The preferable nitrogen source for the cordycepin production was the mixture of peptone and yeast extract, in which the ratio of the yeast extract was 75% or greater. The optimal carbon/nitrogen ratio (w/w) was 2/1 when glucose was used as the carbon source. The lower medium depth resulted in a higher productivity over the present experimental range from 1.8 to 5.3 cm. Under the optimal conditions, the maximum cordycepin concentration in the culture medium reached 640 mg/l, and the maximum cordycepin productivity was 32 mg/(l·day).
Cordyceps militaris dried fruiting bodies were extracted with 5% KOH solution. The extract was purified by freeze-thawing treatment, and dialysis (100 kDa), giving rise to a homogeneous polysaccharide (Mw 23,000 Da). Its monosaccharide composition was mannose (56.7%), galactose (34.5%), and glucose (8.8%). The anomeric configurations were determined by their coupling constants. A complex polysaccharide was identified by NMR and methylation analysis. The HSQC spectrum showed signals at δ 107.7/5.06 and 106.1/5.14; 105.9/5.12 relative to β-d-Galf, and O-2-substituted β-d-Galf units, respectively. The sign at δ 104.4/5.21 corresponded to α-d-Galf. Other signals corresponded to α-d-Manp O-6- and O-2-substituted (δ 100.2/4.94; 100.5/5.27; 100.6/5.23; 100.7/5.16), and α-d-Manp 2,6-di-O-substituted (from δ 99.3 to 99.9). The main linkages, confirmed by methylation analysis, showed the derivatives: 2,3,4-Me3-Manp (11.9%) and 3,4,6-Me3-Manp (28.6%). The branches were (1 → 6)-linked-α-d-Manp or (1 → 2)-linked-β-d-Galf, terminating with β-d-Galf, α-d-Galf, α-d-Galp, or α-d-Manp. 42.7% of the partially hydrolyzed product consisted of 3,4,6-Me3-Manp, suggesting a (1 → 2)-linked backbone.
The methods for increasing the production of cordycepin (3′-deoxyadenosine), which is a kind of nucleoside analogue, were investigated by a surface culture of Cordyceps militaris NBRC 9787 using liquid medium. As a result of adding various compounds such as purine biosynthesis-related compounds, coenzymes and surfactant to the basal medium for the purpose of enhancing the cordycepin production, glycine, l-aspartic acid, l-glutamine, adenine and adenosine were shown to be effective additives. The most preferable condition of the additives was the combination of 1 g/l of adenine and 16 g/l of glycine, and the maximum cordycepin production reached 2.5 g/l, which corresponds to 4.1 times that in the basal medium, and this value was higher compared to other reports. As a more efficient method, the repeated batch operation was shown to be practicable, and the productivity by the repeated batch operation in the optimal medium reached 0.19 g/(l d), which corresponds to 5.5 times that by the batch operation in the basal medium. The nucleic acid-related compounds produced by the surface culture were also analyzed. The Results indicated that about 97% of the cordycepin synthesized by C. militaris was excreted into the culture medium, and the production of cordycepin and guanine might be linked to each other.
The Ascomycete Cordyceps militaris, an entomopathogenic fungus, is one of the most important traditional Chinese medicines. Studies related to its pharmacological properties suggest that this Mushroom can exert interesting biological activities. Aqueous (CW and HW) and alkaline (K5) extracts containing polysaccharides were prepared from this Mushroom, and a β-D-glucan was purified. This polymer was analysed by GC-MS and NMR spectrometry, showing a linear chain composed of β-D-Glcp (1→3)-linked. The six main signals in the 13C-NMR spectrum were assigned by comparison to reported data. The aqueous (CW, HW) extracts stimulated the expression of IL-1β, TNF-α, and COX-2 by THP-1 macrophages, while the alkaline (K5) extract did not show any effect. However, when the extracts were added to the cells in the presence of LPS, K5 showed the highest inhibition of the pro-inflammatory genes expression. This inhibitory effect was also observed for the purified β-(1→3)-D-glucan, that seems to be the most potent anti-inflammatory compound present in the polysaccharide extracts of C. militaris. In vivo, β-(1→3)-D-glucan also inhibited significantly the inflammatory phase of formalin-induced nociceptive response, and, in addition, it reduced the migration of total leukocytes but not the neutrophils induced by LPS. In Conclusion, this study clearly demonstrates the anti-inflammatory effect of β-(1→3)-D-glucan.
A novel fibrinolytic enzyme from Cordyceps militaris, a Chinese traditional Medicinal Mushroom
A novel fibrinolytic enzyme from Cordyceps militaris was purified and partially characterized for the first time, which was designated C.militaris fibrinolytic enzyme (CMase). This extracellular enzyme from C.militaris was isolated by ammonium sulphate fraction, and purified to electrophoretic homogeneity using gel filtration chromatography. The apparent molecular mass of the purified enzyme was estimated to be 27.3kDa by SDS-PAGE. The optimum pH and temperature for the enzyme activity were pH 6.0 and 25°C, respectively. In the presence of metal ions such as Mg2+ and Fe2+ ions the activity of the enzyme increased, whereas EDTA and Cu2+ ion inhibited the enzyme activity. Interestingly the N-terminal amino acid sequences of the enzyme is extremely similar to those of the trypsin proteinases from insects, and has no significant homology with those of the fibrinolytic enzyme from other Medicinal Mushroom. In Conclusion, C.militaris produces a strong fibrinolytic enzyme CMase and may be considered as a new source for thrombolytic agents.
Efficient CRISPR-Cas9 Gene Disruption system in edible–Medicinal Mushroom Cordyceps militaris
Cordyceps militaris is a well-known edible Medicinal Mushroom in East Asia that contains abundant and diverse bioactive compounds. Since traditional genome editing systems in C. militaris were inefficient and complicated, here, we show that the codon-optimized cas9, which was used with the newly reported promoter Pcmlsm3 and terminator Tcmura3, was expressed. Furthermore, with the help of the negative selection marker ura3, a CRISPR-Cas9 system that included the Cas9 DNA endonuclease, RNA presynthesized in vitro and a single-strand DNA template efficiently generated site-specific deletion and insertion. This is the first report of a CRISPR-Cas9 system in C. militaris, and it could accelerate the genome reconstruction of C. militaris to meet the need for rapid development in the Fungi industry.
Cordycepin, an active Constituent of Nutrient
Powerhouse and potential Medicinal Mushroom
Cordyceps militaris Linn., ameliorates age-related
Testicular Dysfunction in Rats
age-related male sexual dysfunction covers a wide variety of issues, together with spermatogenic and testicular impairment. In the present work, the effects of cordycepin (COR), an active constituent of a nutrient powerhouse Cordyceps militaris Linn, on senile testicular dysfunction in rats was investigated. The sperm kinematics, antioxidant enzymes, spermatogenic factors, sex hormone receptors, histone deacetylating sirtuin 1 (SIRT1), and autophagy-related mammalian target of rapamycin complex 1 (mTORC1) expression in aged rat testes were evaluated. Sprague Dawley rats were divided into young control (2-month-old; YC), aged control (12-month-old; AC), and aged plus COR-treated groups (5 (COR-5), 10 (COR-10), and 20 (COR-20) mg/kg). The AC group showed reduced sperm kinematics and altered testicular histomorphology compared with the YC group (p < 0.05). However, compared with the AC group, the COR-treated group exhibited improved sperm motility, progressiveness, and average path/straight line velocity (p < 0.05–0.01). Alterations in spermatogenesis-related protein and mRNA expression were significantly ameliorated (p < 0.05) in the COR-20 group compared with the AC group. The altered histone deacetylating SIRT1 and autophagy-related mTORC1 molecular expression in aged rats were restored in the COR-20 group (p < 0.05). In Conclusion, the Results suggest that COR holds immense nutritional potential and therapeutic value in ameliorating age-related male sexual dysfunctions.
Cordyceps sinensis
The anti-inflammatory and antinociceptive activities of cordymin, a peptide purified from the Medicinal Mushroom Cordyceps sinensis, were studied. The effects of cordymin on cytokine levels and total antioxidant activity were analysed. The antinociceptive effects of cordymin in vivo and in vitro were also determined. Cordymin treatment decreased the levels of tumour necrosis factor alpha, interleukin 1 beta and total antioxidant status. Cordymin inhibited the acetic acid-induced abdominal constrictions in mice in a dose-dependent manner. In the hot-plate test, Results showed that cordymin significantly inhibited the reaction time to thermal stimuli at 30, 60 and 90 min. In neurolysin inhibition assay, cordymin showed strong activities against neurolysin (IC50 = 0.1 µM). Our Results show that cordymin is a potent anti-inflammatory and analgesic medicine.
Cordymin is a peptide purified from the Medicinal Mushroom Cordyceps sinensis. The present study investigated the effects of Cordymin in prevention of focal cerebral ischemic/reperfusion (IR) injury. The right middle cerebral artery occlusion model was used in the study. The effects of Cordymin on mortality rate, neurobehavior, grip strength, glutathione content, lipid peroxidation, glutathione peroxidase activity, glutathione reductase activity, catalase activity, Na+K+ATPase activity glutathione S transferase activity and on the regulation of C3 and C4 protein level, polymorphonuclear cells, interleukin-1β and tumor necrosis factor-α in a rat model were studied respectively. treatment (orally) of Cordymin significantly boosted the defense mechanism against cerebral ischemia by increasing antioxidants activity related to lesion pathogenesis. restoration of the antioxidant homeostasis in the brain after reperfusion may have helped the brain recover from ischemic injury. Moreover, Cordymin significantly inhibited infiltration of polymorphonuclear cells and IR-induced up-regulation of the brain production of C3 protein level, interleukin-1β and tumor necrosis factor-α. Cordymin significantly improved the outcome in rats after cerebral ischemia and reperfusion in terms of neurobehavioral function. Our findings suggest that cordymin have a neuroprotective effect in the ischemic brain, which is due to the inhibition of inflammation and increase of antioxidants activity related to lesion pathogenesis. Cordymin can be used as potential preventive agent against cerebral ischemia-reperfusion injury.
Medicinal Mushroom for prevention of Disease of Modern Civilization
Disease of modern civilization (DMC) such as type 2 diabetes and cardiovascular disease is caused by the pressure and tension, as well as nutritional imbalance, coupled with a lack of exercise, long-term cumulative a class of diseases. Medicinal Mushrooms have diverse morphological, physiological, and ecological characteristics that support their diverse lifestyles. These specific interspecies interactions depend on the production of a wide range of bioactive substances. Medicinal Mushrooms are well recognized for their Medicinal properties and have been used in traditional medicine for millennia.
As a rich source of novel polysaccharides, Cordyceps sinensis (CS), one of the valued traditional Chinese Medicinal Fungi, is a major focus of many natural products research efforts. More than 33 polysaccharides have been characterized till the date. polysaccharides from CS possess a wide spectrum of biological activities like antitumor, antioxidant, immunomodulatory activity, kidney and lung protection, etc. This review covers the recent literature and updates the information on polysaccharides from CS, covering about 130 research articles emphasizing the isolation, characterization of polysaccharides and their biological functions.
Review on yarsagumba (Cordyceps sinensis) – An exotic Medicinal Mushroom
Cordyceps sinensis, popularly known as Yarsagumba, is a rare age old Mushroom that has been valued extensively in traditional Chinese medicine. People of China and Tibet have been using this for various Medicinal purposes since emperors’ age. Its unique life cycle and diverse Medicinal uses compelled science to show interest during last three decades. The present study reviews about its basic knowledge, claimed uses, their scientific backgrounds and its impact on socioeconomic status. Much research work has been carried out leading to isolation of bioactive compounds and many of them undergoing clinical trials too. On the other hand it shows immense effects on the lifestyle and economic status of inhabitants of those high altitude villages where it is found naturally. Despite of its scientific progress, further development is required particularly in formulation of dosage forms and analysis leading to the best utilization of this most costly Medicinal Mushroom.
The aim of this study was to investigate the protective effect of cordymin on diabetic osteopenia in alloxan-induced diabetic rats and the possible mechanisms involved. The diabetic rats received daily intraperitoneal injection with cordymin (20, 50, and 100 mg/kg/day) for 5 weeks. Cordymin could restore the circulating blood glucose, glycosylated hemoglobin (HbA1c), serum alkaline phosphatase (ALP), tartrate resistant acid phosphatase (TRAP), and insulin levels in a dose-dependent manner. Also, the treatment of diabetic rats with cordymin could partially reverse the β cells death and decrease the total antioxidant status (TAOS) in the diabetic rats. The Results may directly and indirectly account for the possible mechanism of the beneficial effect of cordymin on diabetic osteopenia, which was confirmed with the increased bone mineral content (BMC) and bone mineral density (BMD) in diabetic rats ( ). All those findings indicate that cordymin may play a protective role in diabetic osteoporosis.
Cordyceps sobolifera
A novel serine protease, designated as cordysobin, was purified from dried fruiting bodies of the Mushroom Cordyceps sobolifera. The isolation procedure utilized ion exchange chromatography on DEAE-cellulose and SP-Sepharose followed by gel filtration on Superdex 75. The protease did not adsorb on DEAE-cellulose but bound to SP-Sepharose. In sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), the protease resolved as a single band with an apparent molecular mass of 31 kDa. Its optimal pH was 10.0, and the optimal temperature was 65°C. The protease displayed a Km value of 0.41 μM and 13.44 μM·min−1 using Suc-Leu-Leu-Val-Tyr-MCA as substrate at pH 10.0 and 37°C. Protease activity was enhanced by the Fe2+ ion at low concentration range of 1.25–10 mM and was strongly inhibited by Hg2+ up to 1.25 mM. The protease was strongly inhibited by chymostatin and phenylmethylsulfonyl fluoride (PMSF), suggesting that it is a serine protease. It manifested significant inhibitory activity toward HIV-1 reverse transcriptase (RT) with an IC50 value of 8.2 × 10−3 μM, which is the highest anti-HIV-1 RT activity of reported Mushroom proteins.
Cordyceps taii
Cordyceps taii, an edible Medicinal Mushroom native to south China, is recognized as an unparalleled resource of healthy foods and drug discovery. In the present study, the antioxidant pharmacological properties of C. taii were systematically investigated. In vitro assays revealed the scavenging activities of the aqueous extract and polysaccharides of C. taii against various free radicals, that is, 1,1-diphenyl-2-picrylhydrazyl radical, hydroxyl radical, and superoxide anion radical. The EC50 values for superoxide anion-free radical ranged from 2.04 mg/mL to 2.49 mg/mL, which was at least 2.6-fold stronger than that of antioxidant thiourea. The polysaccharides also significantly enhanced the antioxidant enzyme activities (superoxide dismutase, catalase, and glutathione peroxidase) and markedly decreased the malondialdehyde production of lipid peroxidation in a D-galactose-induced aging mouse model. Interestingly, the immune function of the administration group was significantly boosted compared with the D-galactose-induced aging model group. Therefore, the C. taii polysaccharides possessed potent antioxidant activity closely associated with immune function enhancement and free radical scavenging. These findings suggest that the polysaccharides are a promising source of natural antioxidants and antiaging drugs. Consequently, a preliminary chemical investigation was performed using gas chromatography-mass spectroscopy and revealed that the polysaccharides studied were mainly composed of glucose, mannose, and galactose. Fourier-transform infrared spectra also showed characteristic polysaccharide absorption bands.
Coriolus versicolor(CV)
Coriolus versicolor: A Medicinal Mushroom with promising Immunotherapeutic Values
Coriolus versicolor(CV) is a Medicinal Mushroom widely prescribed for the prophylaxis and treatment of cancer and infection in China. In recent years, it has been extensively demonstrated both preclinically and clinically that aqueous extracts obtained from CV display a wide array of biological activities, including stimulatory effects on different immune cells and inhibition of cancer growth. The growing popularity of aqueous CV extracts as an adjunct medical modality to conventional cancer therapies has generated substantial commercial interest in developing these extracts into consistent and efficacious oral proprietary products. While very limited information is available on the physical chemical, and pharmacodynamic properties of the active principles present in these extracts, there has been sufficient scientific evidence to support the feasibility of developing at least some of these constituents into an evidence-based immunodulatory agent. In this article, the background, traditional usage, pharmacological activities, clinical effects, adverse reactions, active constituents, and regulatory aspects of CV are reviewed. Presented also in this review are the current uses and administration, potential drug interactions, and contraindication of aqueous extracts prepared from CV.
bioactive compounds obtained from Coriolus versicolor (Trametes versicolor (L.: Fr) Lloyd, 1920.) Mushrooms cultivated in a stirred-tank bioreactor were tested to determine their antimicrobial potential. extracellular polysaccharides were isolated from the fermentation broth by ethanol precipitation. A methanol extract was prepared from mycelium. The cultivation conditions applied during the fermentation process provided for significant biomass 6.63 ± 0.31 g dry weight L− 1 and yield of extracellular polysaccharides (EPS) (0.74 ± 0.12 g L− 1). Microscopic analyses revealed that the mycelium grew predominately in the form of fluffy pellets. The methanol extract demonstrated very good activity against all the tested Gram-positive bacteria. Bacillus spizizeni and Staphylococcus epidermidis were the most sensitive strains (minimum inhibitory concentration (MIC) < 0.3125 mg mL− 1). Among the Gram-negative bacteria, Yersinia enterocolitica had the lowest MIC value, 5 mg mL− 1. Microbicidal activity of mycelia methanol extract was established in seven out of ten tested Gram-negative bacteria strains with minimum bactericidal concentration (MBC) values ranged from 20 to 40 mg mL− 1. Enterococcus faecalis and Staphylococcus aureus showed higher sensitivity to the extracellular polysaccharides (MIC values 2.5 mg mL− 1). FTIR analysis revealed a more complex chemical composition of the methanol extract compared to EPS, which might explain the better antibacterial activity of the methanol extract.
Our Results suggested that the submerged cultivation of Coriolus versicolor followed by ethanol precipitation of EPS and the methanol extraction of mycelia can be a promising process to obtain biological active compounds with significant antimicrobial activity.
Daedalea gibbosa
Substances from the Medicinal Mushroom
Daedalea gibbosa inhibit kinase activity
of native and T315I mutated Bcr-Abl
human chronic myelogenous leukemia (CML) is a malignancy of pluripotent hematopoietic cells characterized by a distinctive cytogenetic abnormality resulting in the creation of a p210 Bcr-Abl fusion protein with abnormal tyrosine kinase activity. Recently, a selective Abl kinase inhibitor, Imatinib mesylate, was introduced as a first line therapy for CML. Despite the initial response, CML patients develop a resistantance to Imatinib, which is mediated mainly by point mutations within the Abl protein. Herein, we describe the identification of mycelium organic extracts of Daedalea gibbosa with selective anti-proliferating and apoptosis– inducing activities against K562 cells and other laboratory model of CML. Using activity-guided purification, we isolated an active fraction, F6, which inhibits in vitro kinase activity of recombinant Abl. The active fraction significantly inhibits the autophosphorylation of native and mutated Bcr-Abl, which are resistant to Imatinib treatment including the T315I mutation. Using a colony-forming assay, we demon- strated that the active fraction is effective in inhibiting the colony formation of the Ba/F3 cell line harboring either native Bcr-Abl or its mutations, including the T315I mutation. Our data illustrated the potential of natural products in cancer therapeutics.
Daedaleopsis nitida
antioxidant activity of ethanol extract of
Daedaleopsis nitida Medicinal Mushroom from Turkey
antioxidant activity of ethanol extract of Daedaleopsis nitida medicinal mushroom from Turkey *Mustafa Sevindik Department of Biology, Faculty of Science, Akdeniz University, Antalya, Turkey *Corresponding author’s email: [email protected] Abstract In this study, antioxidant potantial, oxidant potantial, oxidative stress index and heavy metal contents of Daedaleopsis nitida (Durieu & Mont.) Zmitr. & Malysheva Mushroom were determined. Total antioxidant status (TAS), total oxidant status (TOS) and oxidative stress index (OSI) were determined using Rel Assay Diagnostics kits. Cr, Cu, Mn, Fe, Ni, Cd, Pb and Zn contents of fruiting bodies of Mushroom were determined by atomic absorption spectrophotometer. As a result of the study, TAS value of Mushroom extract was determined as 6.072 ± 0.067, TOS value was 7.165 ± 0.074 and OSI value was 0.118 ± 0.002. Cr, Cu, Mn, Fe, Ni, Cd, Pb and Zn contents of the fruiting bodies of Mushroom were determined 16.87 ± 0.73, 109.95 ± 2.17, 8.14 ± 0.81, 239.54 ± 14.30, 1.91 ± 0.64, 7.05 ± 0.83, 0.68 ± 0.31 and 55.96 ± 1.07, respectively.
Dictyophora indusiata
antioxidant and anti-inflammatory activities of fruiting bodies of Dyctiophora indusiata
Dictyophora indusiata is an edible Mushroom belongs to Family Phallaceae of Phallales, Basidiomycota. The purpose of this study was to investigate the antioxidant and anti-inflammatory activities of methanol and hot water extracts prepared from fruiting bodies of Dictyophora indusiata. Besides measuring of 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging activity, a reducing power and a chelating activity on ferrous ions were also measured to evaluate the antioxidant activity for those extracts. To measure the anti-inflammatory activities for the extracts, nitric oxide(NO) production from lipopolysaccharide(LPS) treated RAW 264.7 macrophage cells and carrageenan-induced acute hind paw edema of rats were investigated. The Results showed that the extracts have excellent DPPH scavenging and chelating activity on the ferrous ions compared with positive control. The nitric oxide(NO) production in LPS-stimulated RAW 264.7 macrophage cells were decreased as we increased the concentration of the Mushroom extracts. significant reduction of paw edema of rats were observed at 2~6 h after treatment of methanol and hot-water extracts with 50 mg/ kg concentration to the rats which are induced acute hind paw edema by carrageenan administration. Therefore, the exper- imental Results suggested that methanol and hot-water extracts of Dictyophora indusiata fruiting bodies might be used for natural sources of antioxidant and anti-inflammatory agents.
Elaphomyces granulatus (deer truffle)
Cyclooxygenase-2 inhibitory and antioxidant compounds from the truffle Elaphomyces granulatus
The ethanol extract of fruiting bodies of Elaphomyces granulatus, a truffle-like fungus, was evaluated for cyclooxygenase-2 (COX-2) enzyme inhibitory and antioxidant activities. inhibition of COX-2 activity was evaluated in mouse macrophages (RAW 264.7). The extract of E. granulatus caused a 68% inhibition of COX-2 activity at 50 µg/mL. Bioassay-guided investigation led to the isolation and identification of two active compounds, syringaldehyde and syringic acid. Syringaldehyde moderately inhibited COX-2 activity with an IC50 of 3.5 µg/mL, while syringic acid strongly inhibited COX-2 activity with an IC50 of 0.4 µg/mL. The antioxidant activity of the extract and isolated compounds was evaluated in HL-60 cells by the DCFH-DA method. The extract of E. granulatus showed a potent antioxidant effect, with an IC50 of 41 µg/mL. Of the pure compounds, syringic acid displayed a strong antioxidant activity, with an IC50 of 0.7 µg/mL, while syringaldehyde showed no activity in the assay.
Flammulina velutipes
Medicinal Mushrooms as a Source of novel functional Food
As an irreversible and complex degenerative physiological process, the treatment for aging seems strategically necessary, and polysaccharides play important roles against aging owing to their abundant bioactivities. In this paper, the antioxidant and anti-aging activities of Flammulina velutipes polysaccharides (FPS) and its sulfated FPS (SFPS) on d-galactose-induced aging mice were investigated. The in vitro antioxidant activities demonstrated that SFPS had strong reducing power and superior scavenging effects on 2, 2-diphenylpicrylhydrazyl (DPPH), hydroxyl radicals and the chelating activities of Fe2+. The in vivo animal experiments manifested that the SFPS showed superior antioxidant and protective abilities against the d-galactose-induced aging by increasing the antioxidant enzyme activities, decreasing lipid peroxidation, improving the inflammatory response and ameliorating the anile condition of mice. Furthermore, the structural analysis of SFPS was investigated through FT-IR, NMR, and HPLC analysis, and the Results indicated that SFPS was a homogeneous heteropolysaccharide with a weight-average molecular weight of 2.81 × 103 Da. Furthermore, SFPS has also changed in characteristic functional groups and monosaccharide composition compared to FPS. These Results suggested that sulfated modification could enhance the anti-oxidation, anti-aging and protective activities of F. velutipes polysaccharides, which may provide references for the development of functional foods and natural medicines.
The main objective of this work was to purify the exopolysaccharides (EPS) of Flammulina velutipes SF-06 and investigate the relationship between the different purified fractions and bioactive activity. Two fractions (EPS-1 and EPS-2) were separated and purified by DEAE-52 cellulose and Sephadex G-100 cellulose column chromatography. Monosaccharides composition analysis by gas chromatography indicated that EPS, EPS-1 and EPS-2 were heteropolysaccharides in which rhamnose was a major component. Fourier transform infrared (FT-IR) analysis detected furanose-ring in EPS-1 and EPS-2. All fractions possessed considerable antioxidant activity, while EPS-2 has stronger antioxidant activity than EPS and EPS-1 in vitro. The EPS also exhibited potent anti-aging activation in mice, such as increased catalase and total antioxidant capacity, and decreasing the malondialdehyde (MDA) content. Both the antioxidant in vitro and anti-aging in vivo potentials of EPS could be further utilized in the food industry.
This study was performed to evaluate the cognitive-enhancing effect Flammulina velutipes polysaccharides (FVP) by compatibilizing with ginsenosides on D-galactose-induced Alzheimer‘s disease (AD) rats. Results of the Morris water maze test suggested that the cognitive ability of AD rats was significantly elevated after combined treatment with FVP and ginsenosides. Moreover, the anti-oxidant effect was also elevated as reflected by the increased levels of superoxide dismutase, catalase, and glutathione peroxidase and decreased levels of malondialdehyde in the combination group. Terminal deoxynucleotidyl transferase-mediated dUTP biotin nick-end labeling (TUNEL), immunohistochemistry, and Western blot analysis showed that the TUNEL apoptosis cell rate, Bax, cytochrome C, caspase-3, caspase-9, and apoptosis-inducing factor expression levels were obviously decreased, and the Bcl-2 expression levels were obviously increased in the hippocampi of rats treated with FVP and ginsenosides. The Results suggested that the beneficial effect of FVP against AD can be significantly elevated by compatibilizing with ginsenosides. These findings provide scientific evidence supporting the use of FVP as a safe and effective drug to prevent and treat AD.
Antioxidative and renoprotective effects of residue polysaccharides from Flammulina velutipes
Three extractable polysaccharides including Ac-RPS, Al-RPS and En-RPS were extracted from the residue of Flammulina velutipes and their antioxidative and renoprotective effects on STZ-induced mice were investigated. Biochemical and antioxidant analysis showed that the En-RPS had potential effects in decreasing the serum levels of CRE, BUN, ALB and GLU significantly, increasing the renal activities of SOD, CAT and GSH-Px remarkably, and reducing the renal contents of MDA prominently. Furthermore, the histopathological observations also displayed that En-RPS could alleviate kidney damage. These Results demonstrated that En-RPS extracted from the residue of F. velutipes possessed potent antioxidant activities, and could be used as a promising therapeutic agent for inhibiting the progression of diabetic nephropathy. In addition, the monosaccharide compositions of these three RPS were also analyzed.
polysaccharides from Flammulina velutipes
improve scopolamine-induced impairment of
learning and memory of rats
Flammulina velutipes has been reported to be beneficial in learning and memory capabili- ties, but the mechanisms underlying this remain unclear. In this study, Morris water maze and biochemical analyses of rat brain were used to evaluate the effects of F. velutipes poly- saccharides (FVP) on scopolamine-induced learning and memory impairments. Results suggested that FVP significantly decreased the escape latency and total swimming dis- tance of rats in the hidden platform test and increased the numbers of platform crossing and swimming distance of rats in the probe test. Biochemical examinations revealed that FVP significantly elevates SOD and GSH-Px activities, as well as neurotransmitter levels. The increased acetylcholine content owed to the increased acetylcholine acetyltransferase ac- tivity and decreased acetylcholinesterase activity. Moreover, learning and memory associated signalling pathways were activated by FVP elevating the expression of connexin 36 and p-CaMK II. These Results conclusively proved that FVP is a potent agent against the progression of cognitive impairment.
Fomes fomentarius
Mushrooms are known to complement chemotherapy and radiation therapy by countering the side effects of cancer. Recently, there has been great interest in isolation of novel bioactive compounds from Mushrooms due to their numerous health beneficial effects. Chemically water-extractable polysaccharide (MFKF-AP1β), with a molecular weight of 12 kDa, was isolated from fruiting bodies of Mushroom Fomes fomentarius. In this research, we investigated the anti-tumor effects of MFKF-AP1β on human lung carcinoma A549 cells. Results showed that MFKF-AP1β markedly inhibited A549 cell growth in a dose-dependent manner based on the amount of lactate dehydrogenase (LDH) released and morphological alterations. In addition, MFKF-AP1β induced cellular apoptosis by causing single-stranded DNA breakage, as evidenced by apoptosis assay. Furthermore, MFKF-AP1β (25–100 μg/ml) significantly induced single-stranded DNA breakage in A549 cells, as shown by comet assay. Taken together, our Results demonstrate that MFKF-AP1β has strong anti-tumor effects mediated through induction of apoptosis. Therefore, MFKF-AP1β could be useful in lung chemotherapy.
Olive Cake (OC) generated by the olive oil industries, well implanted in Tunisia, represents a major disposal and potentially severe pollution problem. This work presents the study of bioconversion of OC in solid state fermentation with the Medicinal Mushroom, Fomes fomentarius so as to upgrade its nutritional values and digestibility for its use as ruminants feed. The fungus was cultured on OC for 7–30 d, and subsequently the chemical composition, lignocellulolytic enzyme activities and in vitro digestibility of the resultant substrate were determined. The Results obtained showed an increase in the crude protein ranging from 6% to 22% for the control and for treated OC, respectively. significant (P < 0.05) decreases in the values of neutral detergent fiber (hemicelluloses, cellulose and lignin), acid detergent fiber (lignin and cellulose) and acid detergent lignin were detected (23%, 13% and 10%, respectively). The estimated in vitro digestibility improved from 9% (control) to 25% (treated OC). The present findings revealed F. fomentarius to be an efficient organism for lignocellulolytic enzymes production and simultaneous enhancement in crude protein and in vitro digestibility of OC.
Fomitopsis betulina
Differences in anomericity and in the branching degree of glucans lead to characteristic intermolecular association that influences their solubility in water or other solvents. A simple purification approach, based on the glucan solubility in aq. 0.1 M NaOH solution, was applied for the separation of mixed water-insoluble α-D-glucans from β-D-glucans extracted from fruiting bodies of Fomitopsis betulina, which is an underexploited Medicinal Mushroom. The Results indicated that the β-D-glucan is constituted by (1→3)-linked β-D-Glcp units substituted at O-6 by non-reducing β-D-Glcp and (1→6)-linked β-D-Glcp units, while the α-D-glucan has a linear (1→3)-linked glucan structure. Thus, the 0.1 M NaOH treatment proved to be a simple, efficient and low-cost purification method for separation of water-insoluble glucans with different anomeric configurations and degree of branching that were interacting by intermolecular forces.
Cytotoxic triterpenoids and triterpene sugar esters from the Medicinal Mushroom Fomitopsis betulina
Thirteen undescribed 24-methylene lanostane triterpenoids, named polyporenic acids E-M and fomitosides L-O, as well as seventeen known analogues, were isolated from the fruiting bodies of the Mushroom Fomitopsis betulina. Their structures were determined using 1D, 2D NMR, IR, and HRESIMS. Fomitoside L and fomitoside N exhibited cytotoxicity against HL60 leukemia cells (IC50 = 15.8 and 23.7 μM, respectively). Among the known compounds, notable cytotoxicities against HL60 leukemia cells and selectivity with respect to MRC-5 healthy cells were noticed for dehydropachymic acid (IC50 = 10.9 μM, SI 8.6), pachymic acid (IC50 = 11.0 μM, SI 9.8), 3-epi-dehydrotumulosic acid (IC50 = 19.9 μM, SI 5.8) and 12α-hydroxy-3α-(3′-hydroxy-4′-methoxycarbonyl-3′-methylbutyryloxy)-24-methyllanosta-8,24 (31)-dien-26-oic acid (IC50 = 19.2 μM, SI 2.2).
Fomitopsis officinalis
Fomitopsis officinalis (Vill.) Bondartsev & Singer is a rare and endangered Medicinal Mushroom, known in medical practice as agarikon. Strain 5004 of F. officinalis from the IBK Mushroom Culture Collection of M. G. Kholodny Institute of Botany was verified using morphological and molecular genetic techniques. DNA analysis shows 99% identity of the investigated strain to other F. officinalis sequences deposited in NCBI databases. The Results of the study of the biological characteristics of F. officinalis 5004 on agar nutrient media and plant substrates of various compositions are presented. We observed the microstructures of F. officinalis culture using light and scanning electron microscopy. The hyphae have regular unilateral clamp connections of two types: without a slit and rare medallion-type clamps, some anastomoses and mycelial cords as well as blastoconidia after prolonged cultivation (more than 30 days). The incrustation of the hyphae in the form of thin villi is revealed for the first time. The morphology of the mycelial colonies of F. officinalis depended on the composition of the nutrient medium. According to the radial growth rate the culture of investigated species belongs to the Fungi growing very slowly within 0.4–1.9 mm/day. The fastest growth of F. officinalis 5004 was observed on malt agar with the addition of larch sawdust: 1.8 ± 0.1 mm/day. The critical temperature for mycelial growth was 41 ± 0.1 ºC. We tried three variants of plant substrates for fructification: sunflower husk, larch sawdust and larch chips. The substrate composition influenced the vegetative growth and the formation of teleomorph stage. The sunflower husk was the most favorable substrate for the growth of vegetative mycelium. The mycelium had completely colonized this substrate by the 30th day, in contrast to the larch chips, which were only partially colonized (ca. 50%) on 30–40th days of experiment. The fungus developed fruit bodies on both substrates: the sunflower husk and larch chips. The least suitable substrate for vegetative growth of this species was the larch sawdust. After two months of incubation, the mycelium covered only 27% of the visible surface of substrate blocks, with no primordia and fruiting bodies forming. Thus, the obtained mycelium growth parameters on nutrient media, microand macromorphological characteristics can be used as additional taxonomic characteristics of F. officinalis culture in the vegetative stage of growth. The strain ІBK 5004 may become a potential producer for new fungal biotechnologies in Ukraine in the near future.
Ganoderma applanatum (Pers.) Pat.
In the present study, green synthesis and cost effective approach of silver nanoparticles using wild MedicinalMushroom Ganoderma applanatum(Pers.) Pat. from Similipal Biosphere Reserve, Odisha, India is reported. Thebiosynthesised AgNPs were characterised using UV-visible spectroscopy, particle analyser and scanning electronmicroscopy studies. It was found by dynamic light scattering analysis, that the average size and charges of the AgNPswere 133.0 ± 0.361 nm and−6.01 ± 5.30 mV, respectively. Moreover, theFourier transform infrared study was alsoconducted to identify the biomolecules or functional groups responsible for the reduction of Ag and stabilisation of theAgNPs. The potential biomedical application with reference to antimicrobial activity of the synthesised AgNPs wasinvestigated against some pathogenic microorganisms.
Our previous research has shown that lanostane triterpenoids from Ganoderma applanatum exhibit significant anti-adipogenesis effects. In order to obtain more structurally diverse lanostane triterpenoids to establish a structure–activity relationship, we continued the study of lanostane triterpenoids from the fruiting bodies of G. applanatum, and forty highly oxygenated lanostane-type triterpenoinds (1–40), including sixteen new compounds (1–16), were isolated. Their structures were elucidated using NMR spectra, X-ray crystallographic analysis, and Mosher’s method. In addition, some of their parts were evaluated to determine their anti-adipogenesis activities in the 3T3-L1 cell model. The Results showed that compounds 16, 22, 28, and 32 exhibited stronger anti-adipogenesis effects than the positive control (LiCl, 20 mM) at the concentration of 20 μM. compounds 15 and 20 could significantly reduce the lipid accumulation during the differentiation process of 3T3-L1 cells, comparable to the untreated group. Their IC50 values were 6.42 and 5.39 μM, respectively. The combined Results of our previous and present studies allow us to establish a structure-activity relationship of lanostane triterpenoids, indicating that the A-seco-23→26 lactone skeleton could play a key role in anti-adipogenesis activity.
Ganoderma boninense
Six new 3,4-seco-27-norlanostane triterpenes, ganoboninones A–F (1–6), as well as three known compounds ganoboninketals A–C (7–9), were isolated from the fruiting bodies of the Medicinal Mushroom Ganoderma boninense. The structures of 1–6 were established by extensive spectroscopic analysis. compounds 1–6 are new 3,4-seco-27-norlanostane triterpenoids featuring with an interesting tetradecahydrobenzo[4,5]indeno[1,7a-c]furan backbone. The absolute configurations in 1–6 were determined by CD spectral analysis, and ECD calculation. In an in vitro anti-Plasmodium falciparum bioassay, compounds 1, 2, and 6 showed antimalarial effects with IC50 values of 27.36, 15.68, and 2.03 μM, respectively. In a transactivation assay, compounds 5, 7, 8, and 9 showed agonistic activity to LXRβ with EC50 value of 203.00, 8.32, 257.00, and 86.70 nM, respectively.
Ganoderma leucocontextum
Sixteen new lanostane triterpenes, ganoleucoins A–P (1–16), together with 10 known tripterpenes (17–26), were isolated from the cultivated fruiting bodies of Ganoderma leucocontextum, a new member of the Ganoderma lucidum complex. The structures of the new compounds were elucidated by extensive spectroscopic analysis and chemical transformation. The inhibitory effects of 1–26 on HMG-CoA reductase and α-glucosidase were tested in vitro. compounds 1, 3, 6, 10–14, 17, 18, 23, 25, and 26 showed much stronger inhibitory activity against HMG-CoA reductase than the positive control atorvastatin. compounds 13, 14, and 16 presented potent inhibitory activity against α-glucosidase from yeast with IC50 values of 13.6, 2.5, and 5.9 μM, respectively. In addition, the cytotoxicity of 1–26 was evaluated against the K562 and PC-3 cell lines by the MTT assay. compounds 1, 2, 6, 7, 10, 12, 16, 18, and 25 exhibited cytotoxicity against K562 cells with IC50 values in the range 10–20 μM. Paclitaxel was used as the positive control with an IC50 value of 0.9 μM. This is the first report of secondary metabolites from this Medicinal Mushroom.
Ganoderma lingzhi
Heat treatment of Reishi Medicinal Mushroom (Ganoderma
lingzhi) Basidiocarp enhanced Its β-glucan Solubility,
antioxidant Capacity and Lactogenic properties
The effect of heat treatment on dried fruiting bodies of Reishi Medicinal Mushroom (Ganoderma lingzhi) is investigated. Control and samples treated for 20 min at temperatures of 70, 120, 150 and 180 ◦C were subjected for their free radical scavenging capacity, different glucans and total phenolic content determination. The growth rate of Escherichia coli and Lactobacillus casei supple- mented with control and heat-treated samples is also investigated. The roasted Mushroom samples at 150 ◦C and 180 ◦C showed the highest level of β-glucan (37.82%) and free radical scavenging ca- pacity on 2,2-diphenyl-1-picrylhidrazyl (DPPH•) and 2,2-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS•+). The content of total phenolics (TPC) was also influenced by heat treatment and significantly higher TPC values were recorded in samples treated at 120 ◦C and 150 ◦C. The presence of reducing sugars was only detected after heat treatment at 150 ◦C (0.23%) and at 180 ◦C (0.57%). The heat treatments at 120, 150 and 180 ◦C, significantly attenuated the number of colony-forming units (CFU) of pathogenic E. coli, in a linear relationship with an elevated temperature. The sup- plementation of heat-treated Reishi Mushroom at 120 ◦C resulted in the highest growth rate of probiotic L. casei. The obtained Results in this study revealed the significant effect of short-term heat treatment by enhancing the antioxidant capacity, β-glucan solubility and prebiotic property of the dried basidiocarp of Reishi Mushroom.
To contribute towards effective exploitation and utilization of natural antioxidants, response surface methodology (RSM) was employed to optimize the medium composition for the production of exopolysaccharides from the Medicinal Mushroom Ganoderma lingzhi (GLEPS). An optimal medium for GLEPS production was gave through Plackett-Burman design, path of steepest ascent, and Box-Behnken design as follows: glucose (59.62 g/L), yeast extract (10.03 g/L), CaCO3 (0.2 g/L), thiamine (45.13 mg/L), KH2PO4 (1.0 g/L), peptone (1.5 g/L), Tween 80 (10.26 mL/L), ZnSO4 (0.3 g/L), mannitol (1.5 g/L), MgSO4 (0.5 g/L), and aspartate (8.86 g/L). The GLEPS yield obtained was 3.57 ± 0.21 g/L-3.16-fold higher than that produced in basal medium alone. The resulting GLEPS rich in uronic acid, d-mannose, l-rhamnose, and d-glucose, was a heteropolysaccharide with high-molecular weights (475,000 kDa and 21.6 kDa, 87.97%). It was demonstrated that the GLEPS with higher carbohydrate and uronic acid contents exhibited strong in vitro antioxidant activities via radical scavenging, reductive capacity, and chelation of transition metal catalysis. These findings indicated that RSM is an efficient tool to predict the composition of culture medium required for maximizing GLEPS yield, and GLEPS had potent antioxidant activities and could be explored as a novel natural antioxidant in functional food or medicine.
Ganoderma lucidum
Screening of Inhibitory Activity of Edible Mushrooms on Dopamine β−Hydroxylase
Dopamine catalyses the enzymatic reaction of dopamine to norepinephrine. For the purpose of screening DBH inhibitory activity from edible mushrooms, Ganoderma lucidum, Agaricus bisporus and Lentinus edodes were examined by tracing inhibitory activities against bovine adrenal DBH, utilizing tyramine as a substrate. Among the three edible mushrooms tested, Ganoderma lucidum showed potent enzyme inhibitory activilies above 100% against DBH in chloroform fraction. Lentinus edodes and Agaricus bisporus showed inhibitory activities in ethylacetate fraction on 79.7% and 64.7%, respectively. Each solvent fraction of these mushrooms were assessed in the aspects of their inhibitory activities against DBH, and their values were calculated. value of chloroform fraction of Ganoderma lucidum was , and those of ethylacetate fractions of Agaricus bisporus and Lentinus edodes were , respectively.
Ganoderma lucidum (Curt.: Fr.) P. Karst. (Aphyllophoromycetideae)−A Mushrooming Medicinal Mushroom
The medicinal properties of Ganoderma lucidum (Curt.: Fr.) P. Karst. have been recognized for many centuries in China and other parts of Asia. During the last two decades, there has been a sharp increase in the level of commercial interest in G. lucidum products, not only in Asian countries but also in North America and Europe. Latest available estimates put the annual value of G. lucidum products worldwide at more than US $1.6 billion. This increased demand has stimulated improvements in artificial cultivation methods, of which currently the most widely adopted are the wood log, short wood segment, tree stump, sawdust bag, and bottle procedures. The application of modern analytical techniques has revealed the mushroom to contain numerous bioactive compounds including polysaccharides, triterpenes, and immunomodulatory proteins. Many of these compounds have anticancer and antitumor properties that appear to be based on an enhancement of the host immune system rather than on a direct cytocidal effect. Further expansion of the market for G. lucidum products will require the introduction of more reproducible protocols for mushroom production and downstream processing to improve quality control and ensure enduring public trust.
Antimicrobial Activity of the Medicinal Mushroom Ganoderma
Over the past century, a number of synthetic antimicrobial agents have been discovered and developed, but drug resistance and toxicity are still the major hindrances to gaining successful therapeutic outcomes in many instances. Herbal medicines may represent a safe and useful supplement to existing chemotherapeutic therapies for the management of infectious diseases. Ganoderma has traditionally been used to treat chronic infectious diseases, such as chronic hepatitis and bronchitis in Asia, when it is administered alone or more often in combination with chemotherapeutic agents. Preclinical (in vitro and in vivo animal) studies indicate that Ganoderma exhibits a broad spectrum of antibacterial and antiviral activities, whereas data in human beings are scanty. Polysaccharides or triterpenoids from Ganoderma showed activities against Herpes simple virus, Hepatitis B virus, HIV, and Epstein-Barr virus in vitro or in animal models. Ganoderma species also contain antibacterial constituents inhibiting gram-positive and/or gram-negative bacteria in vitro. However, it is difficult to extrapolate these findings to humans, as most of these preclinical studies were conducted under optimized conditions with the use of high doses of Ganoderma components. A double-blind, randomized, placebo-controlled clinical study indicated that treatment of hepatitis B patients with G. lucidum polysaccharides at 5400 mg/day for 12 weeks resulted in significantly decreased serum HBV DNA and hepatitis B e antigen (HbeAg) levels. The mechanisms for the antimicrobial and antiviral activities of Ganoderma are largely undefined. Currently available data do not support the use of Ganoderma as an antibiotic, but it may play an adjunct role for the management of bacterial and viral infection. Further studies are needed in humans.
Ganoderma lucidum (Lingzhi or Reishi) is known as a bitter mushroom with remarkable health benefits. The active constituents found in mushrooms include polysaccharides, dietary fibers, oligosaccharides, triterpenoids, peptides and proteins, alcohols and phenols, mineral elements (such as zinc, copper, iodine, selenium, and iron), vitamins, and amino acids. The bioactive components found in the G. lucidum mushroom have numerous health properties to treat diseased conditions such as hepatopathy, chronic hepatitis, nephritis, hypertension, hyperlipemia, arthritis, neurasthenia, insomnia, bronchitis, asthma, gastric ulcers, atherosclerosis, leukopenia, diabetes, anorexia, and cancer. In spite of the voluminous literature available, G. lucidum is used mostly as an immune enhancer and a health supplement, not therapeutically. This review discusses the therapeutic potential of G. luidum to attract the scientific community to consider its therapeutic application where it can be worth pursuing.
Lingzhi (Ganoderma lucidum) is a woody mushroom highly regarded in traditional medicine and is widely consumed in the belief that it promotes health and longevity, lowers the risk of cancer and heart disease and boosts the immune system. However, objective scientific validation of the putative health benefits of Lingzhi in human subjects is lacking, and issues of possible toxicity must be addressed. The present double-blinded, placebo-controlled, cross-over intervention study investigated the effects of 4 weeks Lingzhi supplementation on a range of biomarkers for antioxidant status, CHD risk, DNA damage, immune status, and inflammation, as well as markers of liver and renal toxicity. It was performed as a follow-up to a study that showed that antioxidant power in plasma increased after Lingzhi ingestion, and that 10 d supplementation was associated with a trend towards an improved CHD biomarker profile. In the present study, fasting blood and urine from healthy, consenting adults (n 18; aged 22 –52 years) was collected before and after 4 weeks supplementation with a com-mercially available encapsulated Lingzhi preparation (1·44 g Lingzhi/d; equivalent to 13·2 g fresh mushroom/d) or placebo. No significant change in any of the variables was found, although a slight trend toward lower lipids was again seen, and antioxidant capacity in urine increased. The results showed no evidence of liver, renal or DNA toxicity with Lingzhi intake, and this is reassuring. The present study of the effects in healthy, well-nourished subjects provides useful, new scientific data that will support controlled intervention trials using at- risk subjects in order to assess the therapeutic effect of Lingzhi in the promotion of healthy ageing.
Complete Mitochondrial Genome of the Medicinal Mushroom Ganoderma lucidum
Ganoderma lucidum is one of the well-known medicinal basidiomycetes worldwide. The mitochondrion, referred to as the second genome, is an organelle found in most eukaryotic cells and participates in critical cellular functions. Elucidating the structure and function of this genome is important to understand completely the genetic contents of G. lucidum. In this study, we assembled the mitochondrial genome of G. lucidum and analyzed the differential expressions of its encoded genes across three developmental stages. The mitochondrial genome is a typical circular DNA molecule of 60,630 bp with a GC content of 26.67%. Genome annotation identified genes that encode 15 conserved proteins, 27 tRNAs, small and large rRNAs, four homing endonucleases, and two hypothetical proteins. Except for genes encoding trnW and two hypothetical proteins, all genes were located on the positive strand. For the repeat structure analysis, eight forward, two inverted, and three tandem repeats were detected. A pair of fragments with a total length around 5.5 kb was found in both the nuclear and mitochondrial genomes, which suggests the possible transfer of DNA sequences between two genomes. RNA-Seq data for samples derived from three stages, namely, mycelia, primordia, and fruiting bodies, were mapped to the mitochondrial genome and qualified. The protein-coding genes were expressed higher in mycelia or primordial stages compared with those in the fruiting bodies. The rRNA abundances were significantly higher in all three stages. Two regions were transcribed but did not contain any identified protein or tRNA genes. Furthermore, three RNA-editing sites were detected. Genome synteny analysis showed that significant genome rearrangements occurred in the mitochondrial genomes. This study provides valuable information on the gene contents of the mitochondrial genome and their differential expressions at various developmental stages of G. lucidum. The results contribute to the understanding of the functions and evolution of fungal mitochondrial DNA.
Ganodermin, an antifungal protein from fruiting bodies of the medicinal mushroom Ganoderma lucidum
A 15-kDa antifungal protein, designated ganodermin, was isolated from the medical mushroom Ganoderma lucidum. The isolation procedure utilized chromatography on DEAE-cellulose, Affi-gel blue gel, CM-Sepharose and Superdex 75. Ganodermin was unadsorbed on DEAE-cellulose and adsorbed on Affi-gel blue gel and CM-Sepharose. Ganodermin inhibited the mycelial growth of Botrytis cinerea, Fusarium oxysporum and Physalospora piricola with an IC50 value of 15.2 μM, 12.4 μM and 18.1 μM, respectively. It was devoid of hemagglutinating, deoxyribonuclease, ribonuclease and protease inhibitory activities.
A laccase from the medicinal mushroom Ganoderma lucidum
A protein demonstrating laccase activity and potent inhibitory activity towards human immunodeficiency virus (HIV)-1 reverse transcriptase (IC50 1.2 μM) was isolated from fresh fruiting bodies of the medicinal mushroom Ganoderma lucidum. The laccase had a novel N-terminal sequence and a molecular mass of 75 kDa, which is higher than the range (55–56 kDa) reported for most other mushroom laccases. It was isolated by sequential chromatography on DEAE-cellulose and Affi-gel blue gel and adsorption on Con A-Sepharose. Unlike some of the previously isolated laccases, it was adsorbed only on Con A-Sepharose. The enzyme required a pH of 3–5 and a temperature of 70°C to exhibit maximal activity. Minimal activity was detected at pH 6 and 7. Activity was undetectable at pH 8 and 9 and after exposure to 100°C for 10 min.
THERAPEUTIC PROPERTIES AND CURRENT MEDICAL USAGE OF MEDICINAL MUSHROOM: GANODERMA LUCIDUM
Mushrooms are an important natural source of food and medicines. Traditionally medicinal properties of mushroom have been well demonstrated particularly in Eastern Asian countries. In modern clinical practices, the bioactive compounds derived from the extract of mushroom sporocarps or mycelium has been widely used for the prevention and treatment of various human diseases such as cancer, diabetes, immune system disorders and infections. Recently, considerable attention is focused on anticarcinogenic bioactive compounds particularly those derived from medicinal or wild mushrooms. The present review analyses the potential therapeutic properties of medicinal mushroom Ganoderma lucidum and their applications in human healthcare.
Two novel ergosterol derivatives, ganodermasides A and B, hydroxylated at C-15 were isolated from the methanol extract of spores of a medicinal mushroom, Ganoderma lucidum, showed to extend the replicative life span of Saccharomyces cerevisiae, a yeast of K6001 strain. The stereostructures of ganodermasides A and B were determined based on the spectroscopic analysis and comparison of spectroscopic data. These new sterols have a 4, 6, 8(14), 22-tetraene-3-one unit with a unique hydroxylation at C-15. The anti-aging activity of these compounds on yeast is comparable to a well-known substance, resveratrol. Based on results of the investigation of the mechanism of biological activity, ganodermasides A and B regulated UTH1 expression in order to extend the replicative life span of yeast.
In the present study, the antibacterial activity of a chloroform extract isolated from the fruiting body of medicinal mushroom Ganoderma lucidum (Ling Zhi or Reishi) was investigated. Different concentrations of the crude extract have been used to evaluate its antibacterial activities against Gram-positive bacteria – Bacillus subtilis ATCC 465, Staphylococcus aureus ATCC25923, Enterococcus feacalis ATCC 29737, and Gram-negative bacteria – Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 85327. The results of disk diffusion tests showed that the chloroform extract had growth inhibitory effects on two of the Gram-positive bacteria. The minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) were determined as well. Both MIC and MBC for Staphylococcus aureus were 8 mg/mL, and for Bacillus subtillis, they were 8 and 16 mg/mL, respectively. To investigate the chloroform extract for its bioactive components, established biochemical methods – the Liebermann-Burchard, Nöller, and Salkowski tests – were used. The results revealed that a variety of lipid derivatives, including sterols and triterpenoid acids, were present in the chloroform extract.
Ganoderma lucidum, a species of the Basidiomycetes class, has been attracting international attention owing to its wide variety of biological activities and great potential as an ingredient in skin care cosmetics including “skin-whitening” products. However, there is little information available on its inhibitory effect against tyrosinase activity. Therefore, the objectives of this study were to investigate the chemical composition of G. lucidum and its inhibitory effects on melanogenesis. We isolated the active compound from G. lucidum using ethanol extraction and ethyl acetate fractionation. In addition, we assayed its inhibitory effects on tyrosinase activity and melanin biosynthesis in B16F10 melanoma cells. In this study, we identified a bioactive compound, ganodermanondiol, which inhibits the activity and expression of cellular tyrosinase and the expression of tyrosinase-related protein-1 (TRP-1), TRP-2, and microphthalmia-associated transcription factor (MITF), thereby decreasing melanin production. Furthermore, ganodermanondiol also affected the mitogen-activated protein kinase (MAPK) cascade and cyclic adenosine monophosphate (cAMP)-dependent signaling pathway, which are involved in the melanogenesis of B16F10 melanoma cells. The finding that ganodermanondiol from G. lucidum exerts an inhibitory effect on tyrosinase will contribute to the use of this mushroom in the preparation of skin care products in the future.
In contrast to the long Chinese history of cultivation of Ganoderma species (ling zhi/reishi), the most important medicinal mushroom in China, growing reishi is a fairly new adventure in North America. In the past decade or so, increasing awareness of the potential health benefits of Ganoderma species led to production of this medicinal mushroom in the United States and Canada. Such interest was triggered primarily by the immune-enhancing property of the mushroom in integrated therapies for immune deficiency syndrome and cancer. In pharmacological studies in the United States, the search for effective antiinflammatory agents for safe long-term use was directed to this ancient medicinal mushroom. Western herbalists took initiatives in studying and using Ganoderma lucidum (Curt.:Fr.P. Karst.) and other species. Growers across the Pacific Ocean chose almost exclusively G. lucidum as the species for cultivation. North American Ganoderma growers are characterized on the basis of product orientation. Features of emerging North American growers are described. Methodology used in Ganoderma cultivation in North America is illustrated, focusing on synthetic log and natural log cultivation. Highlighted is the successful commercial-scale operation of Organotech in San Antonio, Texas. As a reference for growers, stepwise cultivation technology and crop management is covered.
Health Benefits of Ganoderma lucidum as a Medicinal Mushroom
Ganoderma lucidum (Curtis) P. Karst., known as “Lingzhi” in China or “Reishi” in Japan, is a well– known medicinal mushroom and traditional Chinese medicine, which has been used for the prevention and treatment of bronchitis, allergies, hepatitis, immunological disorders and cancer. G. lucidum is rarely collected from nature and mostly cultivated on wood logs and sawdust in plastic bags or bottles to meet the demands of international markets. Diverse groups of chemical compounds with pharmacological activities, isolated from the mycelia and fruiting bodies of G.
lucidum are triterpenoids, polysaccharides (β–D–glucans), proteins, amino acids, nucleosides, alkaloids, steroids, lactones, lectins, fatty acids, and enzymes. The biologically active compounds
as primarily triterpenoids and polysaccharides of G. lucidum have been reported to possess hepatoprotective, antihypertensive, hypocholesterolemic, antihistaminic effects and antioxidant, antitumor, immunomodulatory, and antiangiogenic activities. Several formulations have been developed, patented and used as nutraceuticals, nutriceuticals and pharmaceuticals from G. lucidum’s water or ethanol extracts and rarely purified active compounds. As the result of clinical trials, various products have commercially become available as syrup, injection, tablet, tincture or
bolus of powdered medicine and an ingredient or additive in dark chocolate bars and organic fermented medicinal mushroom drink mixes such as green teas, coffees, and hot cacaos. This review has intended to give and discuss recent knowledge on phytochemical and pharmacological compositions, therapeutic and side effects, clinical trials, and commercial products of G. lucidum
Ganoderma lucidum is a well-known representative of mushrooms that have been used in traditional Chinese medicine for centuries. New discoveries related to this medicinal mushroom and its biological properties are frequently reported. However, only recently have scientists started to pay special attention to G. lucidum spores. This is in part because of the recent development of methods for breaking the spore wall and extracting biocompounds from the spore. Although some research groups are working with G. lucidum spores, data in the literature are still limited, and the methods used have not been systematized. This review therefore describes the main advances in techniques for breaking the spore wall and extracting biocompounds from the spore. In addition, the major active components identified and their biological properties, such as neurological activity and antiaging and cell-protective effects, are investigated because these are of importance for potential drug development.
Two new anti-aging compounds, ganodermasides C and D, were isolated and their structures elucidated. They are novel ergosterols possessing a 4,6,8(14),22- tetraene-3-one unit with unique hydroxylation at C-9. Both of them significantly extended the replicative lifespan of the K6001 yeast strain. Ganodermasides C and D regulated the expression of the gene for UTH1 to prolong the replicative lifespan of yeast.
Ergosterol peroxide is a natural compound of the steroid family found in many fungi, and it possesses antioxidant, anti-inflammatory, anticancer and antiviral activities. The anti-obesity activity of several edible and medicinal mushrooms has been reported, but the effect of mushroom-derived ergosterol peroxide on obesity has not been studied. Therefore, we analyzed the effect of ergosterol peroxide on the inhibition of triglyceride synthesis at protein and mRNA levels and differentiation of 3T3-L1 adipocytes. Ergosterol peroxide inhibited lipid droplet synthesis of differentiated 3T3-L1 cells, expression of peroxisome proliferator-activated receptor gamma (PPARγ) and CCAT/enhancer-binding protein alpha (C/EBPα), the major transcription factors of differentiation, and also the expression of sterol regulatory element-binding protein-1c (SREBP-1c), which promotes the activity of PPARγ, resulting in inhibition of differentiation. It further inhibited the expression of fatty acid synthase (FAS), fatty acid translocase (FAT), and acetyl-coenzyme A carboxylase (ACC), which are lipogenic factors. In addition, it inhibited the phosphorylation of mitogen-activated protein kinases (MAPKs) involved in cell proliferation and activation of early differentiation transcription factors in the mitotic clonal expansion (MCE) stage. As a result, ergosterol peroxide significantly inhibited the synthesis of triglycerides and differentiation of 3T3-L1 cells, and is, therefore, a possibile prophylactic and therapeutic agent for obesity and related metabolic diseases.
Insights of medicinal mushroom (Ganoderma lucidum): prospects and potential in India
Medicinal mushrooms have been used since olden days for the treatment of various diseases. Ganoderma lucidum or Reishi is a medicinal mushroom of significant importance which is gaining popularity due to the presence of numerous bio-active ingredients in it. Wild collection of this mushroom along with its cultivation is done worldwide to meet its everincreasing demand in the market. Although, artificial or sawdust method of its cultivation on different woody substrates is commonly used but wood log cultivation method is also in practice. The steps for its cultivation include spawn preparation, substrate preparation, fruiting body management, harvesting and storage with their own set of requirements and precautions for each step. Several healthcare, personal care, food and beverage products made of its extract are being marketed and consumed worldwide. In this review, a general understanding about the cultivation of medicinal mushroom Ganoderma lucidum, current market scenario and its potential in Indian markets are discussed.
In Vitro Antioxidant Activity of Ethanolic Extract of a Medicinal Mushroom, Ganoderma Lucidum
The aim of the present study was to analyze the antioxidant contents and evaluate the antioxidant potential of Ganoderma lucidum.Materials and Methods:Wild collected G.lucidum was powdered and extracted with ethanol using soxehlet apparatus.Total phenolics,flavones and ascorbic levels were estimated following standard procedures.Subsequently,reducing power,DDPH radical,superoxide,hydroxyl radical and nitric oxide radical scavenging effects of the extracts at different concentrations were evaluated following standard methods. Results:The extract contained 42.41±2.21mg/g of phenolics,13.57±1.57 mg/g of flavones and the ascorbic acid amount was 1.33±0.12 mg/g .Total reducing power of the extract was 1.38 OD/ml at 240mg/ml concentration.DPPH radical scavenging activity was concentration dependent, showing maximum percent inhibition(72.24%) at 250mg/g.Similarly,hydroxyl,superoxide and nitric oxide scavenging potential also at their maximum at higher concentrations.Hydroxyl scavenging effect was 64.69% at 250 mg/g,superoxide radical inhibition was 73.54% at 300 ug/ml and 65.87% inhibition of nitric oxide was noted at 200 mg/ml. Conclusion:Ethanolic extract of G.lucidum showed appreciable amount of antioxidant compounds and also good free radical scavenging effects against different free radicals.The study shows that G.lucidumcompounds can be better antioxidant supplement for nutrients.
Around the world, cancer patients often combine conventional anticancer treatment with complementary alternative medicines derived from natural sources such as fungi and mushrooms, including the popular lingzhi or reishi medicinal mushroom Ganoderma lucidum. Many studies to date have described the anticancer properties of G. lucidum, which are attributed to its major pharmacologically bioactive compounds, such as terpenoids and polysaccharides. Moreover, several scientific observations have suggested a potential beneficial therapeutic strategy using G. lucidum in combination with chemotherapeutic agents to improve therapeutic outcome. However, to my knowledge, no systematic review has been conducted in this area. Therefore, this review summarizes the current knowledge on G. lucidum or its individual components in relation to chemotherapeutic efficacy, ability to reverse multidrug resistance, and chemotherapeutic toxicity.
Oxidative stress (OS) and hypercholesterolemia have been linked with a heightened risk of cardiovascular disease (CVD). Because of the numerous drawbacks of synthetic antioxidants and cholesterol-lowering drugs, natural antioxidative and hypocholesterolemic agents are of immense importance. This study was designed to determine both the OS-attenuating and cholesterol-lowering capacities of the hot water extract (HWE) and of five solvent-solvent- partitioned fractions of Ganoderma lucidum. In vitro antioxidative performance of G. lucidum HWE and fractions was measured through DPPH free radical scavenging, Folin-Ciocalteu assay, lipid peroxidation inhibition, and human low-density lipoprotein (LDL) oxidation inhibition. In vivo antioxidative performance of G. lucidum was assessed by measuring the plasma and liver antioxidative enzymatic activities (catalase, glutathione peroxidase, and superoxide dismutase) in G. lucidum HWE-fed rats. In the CVD tests, the HWE at 200 mg/kg b.w. lowered plasma levels of total cholesterol, triacylglycerol, and LDL cholesterol and increased high-density lipoprotein cholesterol. The current findings indicate the therapeutic potentiality of G. lucidum as an OS-attenuating and hypocholesterolemic agent en route to withstanding CVD complications.
The Lingzhi or Reishi mushroom Ganoderma lucidum is a well-known traditional medicinal mushroom that has been shown to have obvious hepatoprotective effects. The aim of this study was to evaluate the hepatoprotective effects of G. lucidum aqueous extracts (GLEs) on liver injury induced by α-amanitin (α-AMA) in mice and to analyze the possible hepatoprotective mechanisms related to radical scavenging activity. Mice were treated with α-AMA prepared from Amanita exitialis and then administrated with GLE after the α-AMA injection. The hepatoprotective activity of the GLE was compared with the reference drug silibinin (SIL). α-AMA induced a significant elevation in serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities and provoked a significant reduction of superoxide dismutase (SOD) and catalase (CAT) activities and a significant increment of malondialdehyde (MDA) content in liver homogenate. Treatment with GLE or SIL significantly decreased serum ALT and AST levels, significantly increased SOD and CAT activities, and decreased MDA content in liver compared with the α-AMA control group. The histopathological examination of liver sections was consistent with that of biochemical parameters. The results demonstrated that GLE induces hepatoprotective effects on acute liver injury induced by α-AMA; these protective effects may be related in part to the antioxidant properties of GLE.
Bioactive Compounds of the Wonder Medicinal Mushroom “Ganoderma lucidum”
Ganoderma lucidum is a highly praised medicinal mushroom having high demand worldwide. Intense research activities are being carried out on the medicinal applications of this mushroom that include anticancer, antiallergic, antioxidant potential, etc. This wonder mushroom contains many bioactive com- pounds such as polysaccharides, triterpenes, polyphenols, proteins, amino acids, and organic germanium. Ancient Chinese use this mushroom in their medicinal preparations and declared good health and longevity. Health benefits of this mushroom are highly praised in ancient manuscripts. Many pharmaceutical and beauty products made from this mushroom are available in the markets and demands high price. Cultivation and production of this mushroom are limited to certain countries, which leads to an increase in its market value. This chapter describes the details of this special mushroom, including its taxonomy, morphol- ogy, ecological and economic status, cultivation, bioactive molecules, and its medicinal applications.
Ganoderma microsporum
Oral submucous fibrosis (OSF) has been indicated as one of the oral potentially malignant disorders. Epidemiological studies have attributed this pathological fibrosis to the habit of areca nuts chewing, which causes chronic inflammation and persistent activation of myofibroblasts in the oral cavity. Hence, it is crucial to find an effective intervention to ameliorate inflammation in order to prevent the malignant progression of OSF. In this study, we assessed the anti-inflammatory effect of the immunomodulatory protein, GMI, extracted from Ganoderma microsporum on the expression proinflammatory cytokines and the myofibroblast characteristics in human fibrotic buccal mucosal fibroblasts (fBMFs). Our Results demonstrated that the expression level of interleukin (IL)-6 and IL-8 were decreased after exposure of GMI and the myofibroblast activities, including collagen gel contraction, migration, invasion, and wound healing abilities were inhibited as well. Furthermore, we confirmed These findings in the arecoline-stimulated BMFs. Consistent with the above findings, the expression of the myofibroblast marker α-smooth muscle actin and other fibrogenic markers, such as type I collagen, fibronectin, and vimentin in fBMFs were all reduced in a dose-dependent manner. Collectively, our data suggested that GMI suppressed the proinflammatory cytokines and myofibroblast features in fBMFs, and could serve as a promising and natural antifibrosis agent.
Ganoderma neo‐japonicum
Ganoderma neo-japonicum is a well-known Medicinal Mushroom in Asian countries. However, scientific validations on its curative activities are confined to cirrhosis and diabetes. In this study, the anticancer properties of G. neo-japonicum were evaluated using cellular and computational models. The ethanolic extract (EtOH) with a promising inhibitory effect was fractionated into four different fractions: hexane (Hex), chloroform (Chl), butanol (Btn), and aqueous (Aq). The active fractions were then subjected to cell apoptosis assessment and phytochemical profiling. Molecular docking was conducted to elucidate the affinity of selected constituents towards antiapoptotic Bcl-2 protein. The butanol fraction showed the highest antioxidant activities as well as total phenolic content. Both hexane and chloroform fractions exerted a potent cytotoxic effect on colonic carcinoma cells through the induction of apoptosis. phytochemical analysis revealed that the chloroform fraction is terpenoid enriched whereas the hexane fraction comprises predominantly sterol constituents. Stellasterol and 1,25-dihydroxyvitamin D3 3-glycoside were demonstrated to have a high affinity towards Bcl-2 protein. Overall, G. neo-japonicum can be considered as a compelling therapeutic candidate for cancer treatment.
Ganoderma pfeifferi
Determination of in vitro „anti-aging„-effects of Ganoderma pfeifferi
Although the term „anti-aging“ is often used, it is not well defined. We used a perfusion cell culture model [1] for the sensitive detection of real „anti-aging“ effects and demonstrate here the Results obtained with the new Medicinal Mushroom Ganoderma pfeifferi BRES. G. pfeifferi is a European relative of the Medicinal Mushroom Ganoderma lucidum (CURTIS: FR.) P. KARST (Reishi, LingZhi) used in Asian medicine for the prophylaxis and treatment of several disorders including aging processes [2]. A perfusion cell culture was characterised by the continuous addition of fresh nutrient medium and the withdrawal of an equal volume of used medium, allowing the realization of cell cultivation conditions that are approximated as closely as possible to the in vivo situation. We used a human amniotic epithelial cell line (FL cells, ATCC, CCL 62). glucose consumption and lactate production were continuously measured as parameters of cell viability. Because the proliferation of the cells was inhibited by mitomycin the cell number was nearly the same over the whole time of the experiment. Application of extracts of Ganoderma pfeifferi or of Ganoderma Maresome® [3] caused a significant increase in the glucose consumption of the cells and prolonged their life span in comparison to the untreated controls. Whereas the control cells died about 210h after starting of the perfusion cell culture the treated cells live more than 270h. The effects occur also after prophylactic application of the Mushroom preparation and those of Ganoderma pfeifferi are stronger than those of G. lucidum.
Ganoderma sinense
Chapter Nine – Ganoderma sinense polysaccharide: An adjunctive drug used for cancer treatment
anoderma sinense is one of well-known herb medicine and has been used for 2000 years in China. G. lucidum and G. sinense are two family members of Ganoderma, a genus of polypore fungi. In Chinese, “Lingzhi” is designated as G. lucidum or red “Lingzhi” whereas “Zizhi” as G. sinense or purple “Lingzhi.” The polysaccharides or glycans extracted from both G. lucidum and G. sinense have been developed into clinical drugs and recorded in Chinese Pharmacopeia. G. lucidum polysaccharide (GLPS) is one of a few non-hormonal drugs used for treating neurosis, polymyositis, dermatomyositis, atrophic myotonia and muscular dystrophy in China during the past 40 years. In contrast, G. sinense polysaccharide (GSP) tablet is approved as an adjunctive therapeutic drug in China for treating leukopenia and hematopoietic injury caused by concurrent chemo/radiation therapy during cancer treatment by the State Food and Drug Administration (SFDA) in 2010. β-glucan, an established immunostimulanting polysaccharide, is one of the components in GSP. In this study, we will review the biological activities and preclinical studies of GSP in China based on literatures searches from CNKI (China National Knowledge Infrastructure), VIP (Chongqing VIP Chinese Scientific Journals Database), Wanfang database, and PubMed database. Both basic and preclinical studies showed that GSP has antitumor, antioxidant, anticytopenia, and unique mushroom-poison detoxification properties that are different from that of GLPS. Our goal is to provide a molecular picture that would allow in-depth evaluation of GSP as one of few glycan-based drugs that has been used as an immunomodulatory adjunctive drug during cancer therapy.
Ganoderma sinense or “Chinese Lingzhi” is a well-known medicinal fungus in China for more than 2000 years. polysaccharide is the main immunomodulatory and antitumor component in G. sinense. In 2010, G. sinense polysaccharide (GSP) tablet is approved as an adjunctive therapeutic drug in China for treating leukopenia and hematopoietic injury caused by concurrent chemo/radiation therapy during cancer treatment by the State Food and Drug Administration (SFDA). β-glucan, an established immunostimulant, is one of the components in GSP. Based on CNKI (China National Knowledge Infrastructure), VIP (Chongqing VIP Chinese Scientific Journals Database), Wanfang database, and PubMed searches, we have not only summarized but also translated all the basic and preclinical studies about GSP published in Chinese into English in this review article. Unfortunately, all the clinical studies about GSP tablet could not be found during the search or by contacting the drug manufacturers. However, both basic and preclinical studies showed that GSP has antitumor, antioxidant, anticytopenia, and unique mushroom-poison detoxification properties that are different from that of G. lucidum polysaccharide, another “Lingzhi” polysaccharide. The structure and molecular mechanisms of GSP are also discussed. This article urges availability of clinical study results of GSP tablet that would allow in-depth evaluation if the tablet is appropriate to serve as an immunomodulatory drug during cancer therapy at world stage.
High phenotypic plasticity of Ganoderma sinense (Ganodermataceae, Polyporales) in China
Ganoderma is a typical polypore genus which has been used in traditional medicines for centuries and is increasingly being used in pharmaceutical industries worldwide. The genus has been extensively researched due to its beneficial medicinal properties and chemical constituents. However, the taxonomy of Ganoderma remains unclear, and has been plagued by confusion and misinterpretations. During an extensive survey of Ganoderma we were found 20 G. sinense specimens from China. The specimens were identified as G. sinense with the aid of molecular phylogenetic evidence. The studied specimens exhibit phenotypic plasticity due to extrinsic factors, even though they possess identical nucleotide sequences. Seven sequences derived from this study have a single nucleotide polymorphism located at position 158 in ITS1 region and all G. sinense collections clustered in the same species clade. The specimens are each described, illustrated with coloured photographs and compared to similar taxa. We provide a phylogenetic tree for Ganoderma based on ITS, SSU, LSU and RPB2 sequence data and the taxonomic status of G. sinense is discussed.
A protein-bound polysaccharide (GSP-4) with a molecular weight of 8.3 × 105 Da, was isolated from the water extract of the fruiting bodies of Ganoderma sinense. Chemical study revealed that this fraction was composed of mannose, glucose and galactose in the molar ratio of 4.7:27.1:1.0, with the sugar residues of t-, 1,3-, 1,4-, 1,6-, 1,3,4- and 1,3,6-linked Glcp, t-linked Galp, and 1,6-linked Manp. The immnomodulatory effects of GSP-4 were assessed using human peripheral blood mononuclear cells (PBMCs) and murine monocyte/macrophage cell line RAW 264.7. We found that GSP-4 could significantly stimulate the production of the immunomodulatory markers tumor necrosis factor α (TNF-α), interleukin (IL)-1β, IL-12, and granulocyte-macrophage colony-stimulating factor (GM-CSF) in PBMCs. This observation was further substantiated in RAW 264.7 cells, as indicated by the increase of nitric oxide (NO), TNF-α and IL-6 production. GSP-4 also enhanced the expression of inducible NO synthase mRNA in dose-dependent manner. Our current finding gives the first piece of evidence to support that GSP-4 possesses some promising immunomodulating effects and it could be a potential candidate to be further used in related cancer immunotherapy.
Immunomodulatory Activities of Ganoderma sinense polysaccharides in Human Immune Cells
Medicinal mushrooms have been traditionally used as food nutrient supplements in China for thousands of years. The present study aimed to evaluate the immunomodulatory activities of Ganoderma sinense (GS), an allied species of G. lucidum, using human peripheral blood mononuclear cells (PBMC). Our results showed that the polysaccharide-enriched fraction of GS hot water extract (400 μg/ml) exhibited significant stimulatory effects on PBMC proliferation. When the fruiting bodies of GS were divided into pileus and stipe parts and were separately extracted, the GS stipe polysaccharide-enriched fraction (50–400 μg/ml) showed concentration-dependent immunostimulating effects in PBMC. The productions of tumor necrosis factor-α, interleukin (IL)-10, and transforming growth factor -β were significantly enhanced by this fraction. In addition, the proportion of CD14+ monocyte subpopulation within the PBMC was specifically increased. The IL-10 and IL-12 productions in monocyte-derived dendritic cells were significantly enhanced by GS stipe fraction. The composition of monosaccharides of this fraction was determined by ultra performance liquid chromatography and ion exchange chromatography. Our study demonstrated for the first time the immunostimulatory effects of GS stipe polysaccharide-enriched fraction on PBMC and dendritic cells. The findings revealed the potential use of GS (especially including the stipes of fruiting bodies) as adjuvant nutrient supplements for patients, who are receiving immunosuppressive chemotherapies.
Grifola frondosa
antidiabetic and antioxidant activities of Eight Medicinal Mushroom species from China
The objective of the current study was to verify antidiabetic effects of different types of Mushrooms as folk medicines in treating diabetes. The antidiabetic effects were evaluated by in vitro α-glycosidase and aldose reductase (AR) inhibitory assays and antioxidant activity assay. Ganoderma lucidum extract exhibited the best dose-dependent inhibitory activity against α-glycosidase with IC50 at 4.88 mg/mL, and also exhibited aldose reductase inhibitory potential with IC50 value of 9.87 mg/mL. Tremella fuciformis demonstrated the highest AR inhibitory activity (IC50=8.39 mg/mL). antioxidant activities of selected Mushrooms were evaluated based on the total phenolic content (TPC), total flavonoids content (TFC), and DPPH free radical scavenging activity. The result showed that G. lucidum contained the highest TPC (39.3 mg GAE/g sample extract), TFC (15.1 mg CE/g sample extract), and the strongest DPPH free radical scavenging activity (IC50=3.66 mg/mL) among the Mushroom samples.
A key characteristic of Mushroom polysaccharides that elicit an immunomodulatory response is that they are rich in β-glucans and low in α-glucans. In this study we analysed nine commercially available preparations from three Mushroom species, Reishi (Ganoderma lucidum), Shiitake (Lentinula edodes) and Maitake (Grifola frondosa), for β- and α-glucan content. Based on β- and α-glucan content we selected three extracts to combine into a formula and evaluated the ability of the individual extracts and formula to impact on the expression of cytokines IL-1α, IL-6, IL-10 and TNF-α in human macrophages with and without LPS stimulation. The majority of Mushroom extracts and the formula were found to be highly potent immuno-stimulators possessing EC50 values lower than 100 μg/mL. Interestingly the Mushroom formula had lower EC50 values in TNF-α expression from LPS stimulated macrophages compared to the individual extracts, suggesting a potential synergistic effect of the Mushroom formula. A response additivity graph and curve-shift analysis illustrated that indeed the Mushroom formula exhibited an immuno-stimulatory synergistic effect on the expression of the majority of cytokines evaluated in both LPS stimulated and non-stimulated human macrophages, with IL-10 having an antagonistic response. This study represents the first report of a synergistic immuno-modulatory response in human macrophages elicited from a Mushroom formula rationally derived from β- and α-glucan content.
Grifola frondosa (GF), a high value Medicinal Mushroom in China and Japan, is popularly consumed as traditional medicines and health foods, especially for enhancing immune functions. In this study, our aim was to examine the immunomodulatory activities of GF and its bioactive compound ergosterol peroxide (EPO) in lipopolysaccharide (LPS)-induced human monocytic (THP-1) cells. At low concentrations, EPO but not other extracts showed a full protection against LPS-induced cell toxicity. EPO significantly blocked MyD88 and VCAM-1 expression, and cytokine (IL-1β, IL-6 and TNF-α) production in LPS-stimulated cells. It also effectively inhibited NF-κB activation, which was further confirmed with siRNA treatment. These Results Conclude that EPO may play an important role in the immunomodulatory activity of GF through inhibiting the production of pro-inflammatory mediators and activation of NF-κB signaling pathway.
Grifola gargal Singer
Amelioration of atherosclerosis by the New Medicinal Mushroom Grifola gargal Singer
The beneficial effects of edible Mushrooms for improving chronic intractable diseases have been documented. However, the antiatherogenic activity of the new Medicinal Mushroom Grifola gargal is unknown. Therefore, we evaluated whether Grifola gargal can prevent or delay the progression of atherosclerosis. atherosclerosis was induced in ApoE lipoprotein-deficient mice by subcutaneous infusion of angiotensin II. Grifola gargal extract (GGE) was prepared and intraperitoneally injected. The weight of heart and vessels, dilatation/atheroma formation of thoracic and abdominal aorta, the percentage of peripheral granulocytes, and the blood concentration of MCP-1/CCL2 were significantly reduced in mice treated with GGE compared to untreated mice. By contrast, the percentage of regulatory T cells and the plasma concentration of SDF-1/CXCL12 were significantly increased in mice treated with the Mushroom extract compared to untreated mice. In vitro, GGE significantly increased the secretion of SDF-1/CXCL12, VEGF, and TGF-β1 from fibroblasts compared to control. This study demonstrated for the first time that Grifola gargal therapy can enhance regulatory T cells and ameliorate atherosclerosis in mice.
Handkea utriformis
To Heal or Not to Heal? Medicinal Mushrooms Wound Healing
Capacities
Several compounds are responsible for the therapeutic activities of many Medicinal Mushrooms genera; the main groups of these compounds are polysaccharides, terpenes, phenolic compounds, and essential amino acids, as well as minerals such as such as calcium, potassium, magnesium, iron, and zinc.In this review we focused on the wound healing promoting effect of some Medicinal Mushrooms of interest including: Handkea utriformis,Hericium erinaceus, Morchella esculenta, Sparassis crispa and Agaricus blazei.
Helvella crispa
The first report of Helvella crispa (Ascomycota, Pezizales), a rare fungal species in Sri Lanka
Two striking, stipitate fruiting bodies of a fungus were found in Hantana area, bordering the Dunumadalawa Forest Reserve within the Kandy District (Central Province) of Sri Lanka. The apothecium was capitate, cap whitish and irregularly saddle-shaped; the stipe simple, shallowly ribbed, tapering and internally solid. The fruiting bodies were identified, using morphological characteristics, as Helvella crispa belonging to the family Helvellaceae, Order Pezizales and Phylum Ascomycota. This is the first record of H. crispa or the genus Helvella in Sri Lanka. The genus could also be rather rare in Sri Lanka (then Ceylon) as it has not been encountered over 230 year-long history of mycological work in the country.
antibacterial activity of wild Mushrooms from France
We selected seven wild Basidiomycota and Ascomycota Mushrooms to evaluate their antibacterial activity: Cyclocybe aegerita, Cortinarius traganus, Gyroporus castaneus, Neoboletus luridiformis, Rubroboletus lupinus, Gyromitra esculenta, and Helvella crispa. Four Mushrooms, three of which have not been tested to date, displayed antibacterial potential, with a minimal inhibition concentration (MIC) of ≤ 125 μg/mL against at least one Gram-positive bacterial strain. Cyclohexanic extract of G. esculenta possessed the strongest antibacterial activity, with an MIC of 31 μg/mL against two strains of Staphylococcus aureus.
Determination of antioxidant activities of Some wild Mushrooms species in Tokat Region
wild edible Mushrooms can be eaten for health and play an important role in maintaining a healthy life by creating synergy due to the various bioactive components it contains. However, many species that may contain bioactive compounds have not been investigated.
The purpose of this study was to investigate the antioxidant capacity of wild Mushroom species which are grown in Tokat region with names Leatiporus sulpherus, Ramaria sp., Cantharellus aerruginascens, Verpa conica, Verpa bohamica, Tricholoma terreum, Agaricus sp., Helvella elastica in vitro. In addition, total phenolic compound and vitamin E levels were analyzed in Mushroom samples. In order to determine the antioxidant capacity of Mushroom samples, free radical scavenging activity (DPPH), reducing power activity and ABTS•+ [2,2´-Azino-bis (3-ethylbenzothiazoline-6-sulfonic acid)] cation radical scavenging activity analyzes were performed.
The Results were compared with concentrations of Butylated hydroxy toluene (BHT), Butylated hydroxy anisole (BHA) and α-tocopherol. Consequently, the Mushroom species with the highest radical removal activity are Ramaria sp., V. bohamica and H. elastica, respectively. The highest value of vitamin E, was found in Agaricus sp. (1444.1 mg/kg), C. aerruginascens (1370.8 mg/kg) and Ramaria sp. (1204.2 mg/kg) respectively. The highest amount of total phenolic contains was found to be in the Ramaria sp. (6.57 g/kg). These Results may encourage further studies to assess nutritional and Medicinal properties of selected Mushroom species.
antioxidants in wild Mushrooms
Maintenance of equilibrium between free radical production and antioxidant defences (enzymatic and non enzymatic) is an essential condition for normal organism functioning. When this equilibrium has a tendency for the production of free radicals we say that the organism is in oxidative stress. In this situation, excess free radicals may damage cellular lipids, proteins and DNA, affecting normal function and leading to various diseases. In aerobic organisms, the free radicals are constantly produced during the normal cellular metabolism, mainly in the form of Reactive Oxygen species (ROS) and Reactive Nitrogen species (RNS). Exposition of the organism to free radicals has led to the development of endogenous defence mechanisms to eliminate them. These defences were the response of evolution to the inevitability of ROS production in aerobic conditions. natural products with antioxidant activity may help the endogenous defence system. In this perspective the antioxidants present in the diet assume a major importance as possible protector agents reducing oxidative damage. Particularly, the antioxidant properties of wild Mushrooms have been extensively studied by our research group and by others, and many antioxidant compounds extracted from these sources have been identified, such as phenolic compounds, tocopherols, ascorbic acid, and carotenoids. We will review the compounds identified so far in Mushrooms, as well as the mechanism of action involved in their antioxidant properties. wild Mushrooms might be used directly in diet and promote health, taking advantage of the additive and synergistic effects of all the bioactive compounds present.
antioxidant activity of Indigenous edible Mushrooms
The current study was undertaken to measure the antioxidant potential from water and methanolic extracts of fruiting bodies of 23 species of Mushrooms naturally grown in different geographic locations of India. The antioxidant ability of each species was analyzed for the total antioxidative status, employing multimechanistic antioxidative assays such as inhibition of lipid peroxidation, determination of reducing power, and free radical scavenging ability, in addition to determination of total phenolics and identification of phenolic acids by HPLC analysis, because the phenolics are known to contribute largely to antioxidant potential. The antioxidant potential of these varieties of Mushrooms was determined by summing the antioxidative activity (AOA) of each variety by varied antioxidant assays followed by determining the relative percent of AOA defined as the “antioxidant index” (AI). On the basis of the AI, the Mushroom species were graded as very high, high, moderate, and low. Termitomyces heimii was identified as the best variety, which showed 100% AI with 37 mg of phenolics/g of sample, 418 units of reducing power ability (RPA)/g, and an IC50 of ∼1.1 mg (dry weight)/mL, free radical scavenging activity (FRS) in the water extract followed by 11.2 mg of phenolics/g, 275 units of RPA/g, and an IC50 of ∼2.7 mg (dry weight)/mL of FRS in the methanolic extract. Following T. heimii, Termitomyces mummiformis exhibited an AI of 86% within the “very high” group. potent inhibitions of lipid peroxidation of ∼100 and 69% was also observed in T. heimii and T. mummiformis, respectively. Water extracts ranged from 34 to 49% and methanolic extracts varied from 20 to 32% on dry weight of Mushroom fruiting body. Total phenolic compounds were higher in the water extracts (2−37 mg/g) than in methanolic extract (0.7−11.2 mg/g). The AOA measured in the water extract was better than that from the methanolic extract. HPLC analysis of phenolic acids in the two Mushroom species, namely, T. heimii and T. mummiformis, displaying maximum AOA potential indicated a preponderance of tannic acid, gallic acid, protocatacheuic acid, and gentisic acid. Studies thus provide the precise antioxidant status of 23 indigenous species of Mushrooms, which can serve as a useful database for the selection of Mushrooms for the function of preparation of Mushroom-based nutraceutics.
Isolation of metabolites from the wild Mushrooms Helvella lacunosa and Helvella crispa
wild Mushrooms are good sources of a wide range of metabolites that can exhibit diverse nutritional and Medicinal properties. Very few species of wild Mushrooms have been extensively investigated for their activities. The present work, in a continuation of our research for the isolation of new metabolites from wild Mushrooms, focuses on the investigation of two species of Ascomycetes Helvella lacunosa and Helvella crispa, which belong to the family Helvellaceae. Both species are considered edible, although they are regarded as suspicious for gastrointestinal symptoms to some people.
The species H. lacunosa and H. crispa were collected in Mt. Parnitha from Abies cephalonica. In the lab the specimens were lyophilized and finally extracted. H. lacunosa was first extracted with a Supercritical Fluid Extractor using CO2 and then with Accelerated Solvent Extractor (ASE) using EtOH. H. crispa was extracted directly with Accelerated Solvent Extractor using EtOH as a solvent.
Subsequently, the fractionation and investigation of H. lacunosa supercritical extract lead to the isolation and identification of hexadecanoic acid, octadecanoic acid, linoleic acid, oleic acid, hexadecanoic acid ethyl ester, oleic acid methyl ester, oleic acid ethyl ester, linoleic acid ethyl ester, crinosterol and squalene. The extract from the ASE lead to the isolation of hexadecanoic acid, octadecanoic, eicosanoic, docosanoic and tetracosanoid acid. In addition, crinosterol and mannitol were found to be the major compound of this extract. The investigation of the EtOH extract of Helvella crispa lead to the isolation of crinosterol, oleic acid butyl ester, octadecanoic acid butyl ester and mannitol.
Those findings indicate that both species H. lacunosa and H. crispa are good sources of some essential fatty acids and may support to their nutritional value.
Helvella atra Holmsk
It is rich in various vitamins, such as thiamine, riboflavin, niacin, ascorbic acid, ergosterol, folic acid, pantothenic acid, etc. Riboflavin, nicotinic acid, ascorbic acid and ergosterol are particularly rich. The vitamin C in most wild fungi is several to dozens of times higher than that in fruits and vegetables, and the content of vitamin B1 is higher than that in general plant foods; The content of vitamin B12 is higher than that of meat. It can prevent pernicious anemia, improve neural function and reduce blood fat; ergosterol is abundant in Saddleback fungus, which can be converted into vitamin D after ultraviolet radiation.
Diversity and Medicinal Value of Mushrooms from the Himalayan Region, India
Mushrooms being considered as ‘elixir of life’ are valued for their culinary and therapeutic purpose throughout the world. They are widely appreciated as human food for centuries and represent an untapped reservoir of bioactive metabolites. This chapter gives a comprehensive overview on the diversity and indigenous knowledge of wild and cultivated mushrooms in Himalayan region of India. The diverse topographical features and altitudinal variation in Himalayan region of India favours luxuriant biodiversity, assemblage and distribution of macrofungi. The Himalayan belt of India encompasses north western region including the states Jammu and Kashmir, Himachal Pradesh and Uttarakhand and north east- ern region including Sikkim, Arunachal Pradesh, West Bengal and Assam. The accumulated knowledge summarised in this chapter also focuses on the thera- peutic benefits of mushroom related to their biological activity. The present study will serve as a foundation for further research on the exploration and utilisation of mushrooms in India.
Helvella atra König: Fries Nomenclature and typification
Summary: Helvella atra is a sanctioned name and it cannot be replaced by other names, not even by Helvella nigricans Pers., which is also illegitimate. The search for the original meaning of the name shows the value of the choice in lectotypification made by Dissing in 1966.
Hericium erinaceus
Hericium erinaceus, an amazing Medicinal Mushroom
Medicinal Mushrooms have become a compelling topic because the bioactive compounds they contain promise a plethora of therapeutic properties. Hericium erinaceus commonly known as “Houtou” or “Shishigashira” in China and “Yamabushitake” in Japan, has commonly been prescribed in traditional Chinese medicine (TCM), because its consumption has been shown to be beneficial to human health. The species is found throughout the northern hemisphere in Europe, Asia, and North America. Hericium erinaceus has been firmly established as an important Medicinal Mushroom and its numerous bioactive compounds have been developed into food supplements and alternative medicines. However, the correspondence of the active components that cause the observed effects is often not clear. The Mushroom as well as the fermented mycelia have been reported to produce several classes of bioactive molecules, including polysaccharides, proteins, lectins, phenols, and terpenoids. Most interestingly, two classes of terpenoid compounds, hericenones and erinacines, from fruiting bodies and cultured mycelia, respectively, have been found to stimulate nerve growth factor (NGF) synthesis. In this review we examine the scientific literature to explore and highlight the scientific facts concerning Medicinal properties of H. erinaceus. We provide up-to-date information on this Mushroom, including its taxonomy and a Summary of bioactive compounds that appear related to the therapeutic potential of H. erinaceus.
The well-known edible and Medicinal Mushroom Hericium erinaceus produces various bioactive secondary metabolites. Ten new isoindolin-1-ones, named erinacerins C–L (1–10), together with (E)-5-(3,7-dimethylocta-2,6-dien-1-yl)-4-hydroxy-6-methoxy-2-phenethylisoindolin-1-one (11) were isolated from the solid culture of H. erinaceus. The structures of new metabolites were established by spectroscopic methods. The absolute configurations of 3, 4, 9, and 10 were assigned by comparing their specific rotations with those of related phthalimidines (13–20). compounds 5 and 6, 7 and 8, and 9 and 10 are double-bond positional isomers. In a α-glucosidase inhibition assay, compounds 2–11 showed inhibitory activity with IC50 values ranging from 5.3 to 145.1 μM. Preliminary structure–activity analysis indicated that the terpenoid side chain and the phenolic hydroxy groups contributed greatly to the α-glucosidase inhibitory activity of 1–11. In a cytotoxicity assay, compound 11 also presented weak cytotoxicity against two cell lines, A549 and HeLa, with IC50 values of 49.0 and 40.5 μM.
Although the Medicinal Mushroom Hericium erinaceus is used extensively in traditional Chinese medicine to treat chronic superficial gastritis, the underlining pharmaceutical mechanism is yet to be fully understood. In this study, minimum inhibitory concentration (MIC) values of extracts prepared from the fruiting bodies of 14 Mushroom species (H. erinaceus, Ganoderma lucidum, Cordyceps militaris, Pleurotus eryngii, P. ostreatus, Agrocybe aegerita, Lentinus edodes, Agaricus brasiliensis, A. bisporus, Coprinus comatus, Grifola frondosa, Phellinus igniarius, Flammulina velutipes, and Hypsizygus marmoreus) were determined against Helicobacter pylori using laboratory strains of ATCC 43504 and SS1 as well as 9 clinical isolates via an in vitro microplate agar diffusion assay. Ethanol extracts (EEs) of 12 Mushrooms inhibited the growth of H. pylori in vitro, with MIC values <3 mg/mL. EEs of H. erinaceus and G. lucidum also inhibited Staphylococcus aureus (MIC 7360;10 mg/mL) but had no effect on the growth of two Escherichia coli test strains (MIC >10 mg/mL). MIC values of ethyl acetate fractions (EAFs) of H. erinaceus against 9 clinical isolates of H. pylori ranged between 62.5 and 250 µg/mL. The bacteriostatic activity of EAFs was found to be concentration-dependant, and the half maximal inhibitory concentration and minimum bactericidal concentration values for H. pylori ATCC 43504 were 73.0 and 200 µg/mL, respectively. The direct inhibitory effect of EEs and EAFs of H. erinaceus against H. pylori could be another pharmaceutical mechanism of Medicinal Mushrooms−besides the immunomodulating effect of polysaccharides, suggested previously−in the treatment of H. pylori-associated gastrointestinal disorders. Further research to identify the active component(s) is currently undertaking in our laboratory.
neurotrophic factors are important in promoting the growth and differentiation of neurons. Nerve growth factor (NGF) is essential for the maintenance of the basal forebrain cholinergic system. Hericenones and erinacines isolated from the Medicinal Mushroom Hericium erinaceus can induce NGF synthesis in nerve cells. In this study, we evaluated the synergistic interaction between H. erinaceus aqueous extract and exogenous NGF on the neurite outgrowth stimulation of neuroblastoma-glioma cell NG108-15. The neuroprotective effect of the Mushroom extract toward oxidative stress was also studied. Aqueous extract of H. erinaceus was shown to be non-cytotoxic to human lung fibroblast MRC-5 and NG108-15 cells. The combination of 10 ng/mL NGF with 1 μg/mL Mushroom extract yielded the highest percentage increase of 60.6% neurite outgrowth. The extract contained neuroactive compounds that induced the secretion of extracellular NGF in NG108-15 cells, thereby promoting neurite outgrowth activity. However, the H. erinaceus extract failed to protect NG108-15 cells subjected to oxidative stress when applied in pre-treatment and co-treatment modes. In Conclusion, the aqueous extract of H. erinaceus contained neuroactive compounds which induced NGF-synthesis and promoted neurite outgrowth in NG108-15 cells. The extract also enhanced the neurite outgrowth stimulation activity of NGF when applied in combination. The aqueous preparation of H. erinaceus had neurotrophic but not neuroprotective activities.H. erinaceus
Nerve crush injury is a well-established axonotmetic model in experimental Regeneration studies to investigate the impact of various pharmacological treatments. Hericium erinaceus is a temperate Mushroom but is now being cultivated in tropical Malaysia. In this study, we investigated the activity of aqueous extract of H. erinaceus fresh fruiting bodies in promoting functional recovery following an axonotmetic peroneal nerve injury in adult female Sprague-Dawley rats by daily oral administration. The aim was to investigate the possible use of this Mushroom in the treatment of injured nerve. functional recovery was assessed in behavioral experiment by walking track analysis. Peroneal functional index (PFI) was determined before surgery and after surgery as rats showed signs of recovery. Histological examinations were performed on peroneal nerve by immunofluorescence staining and neuromuscular junction by combined silver-cholinesterase stain. Analysis of PFI indicated that return of hind limb function occurred earlier in rats of aqueous extract or mecobalamin (positive control) group compared to negative control group. Regeneration of axons and reinnervation of motor endplates in extensor digitorum longus muscle in rats of aqueous extract or mecobalamin group developed better than in negative control group. These data suggest that daily oral administration of aqueous extract of H. erinaceus fresh fruiting bodies could promote the Regeneration of injured rat peroneal nerve in the early stage of recovery.
Hericium erinaceus is a culinary–Medicinal Mushroom that is used in traditional medicine, in folk medicine, and as Medicinal cuisine in Asian countries such as China, Japan, and Korea. H. erinaceus exhibits various pharmacological properties, such as anti-cancer, immunomodulation, anti-dementia, and anti-gastric ulcer effects. The extracts of the fruiting body of H. erinaceus demonstrate anti-gastritis activity. However, the active principle in the extract, as well as the mechanism to treat gastric ulcers, remains uncertain. The current study aims to identify the active component, with anti-gastric ulcer function, from the extracts of the H. erinaceus mycelium culture. In the experiment, anti-gastric ulcer activity was evaluated using an ethanol-induced ulcer model in mice and with an 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assay using MC cell lines. The Results suggest that the polysaccharide fraction can significantly decrease the ulcerated area compared with the control group and the effect is fairly dose dependent, irrespective of animal or cell experiments. These Results indicate that the polysaccharide fraction is the active component of the H. erinaceus mycelium culture, which protects against gastric ulcers.
Whole genome sequence of an edible and Medicinal Mushroom, Hericium erinaceus (Basidiomycota, Fungi)
Hericium erinaceus is a well-known culinary and Medicinal Mushroom in China. The biological and genetic studies on this Mushroom is rare, thereby hindering the breeding of elite cultivars. Herein, we performed de novo sequencing and assembly of H. erinaceus monokaryon CS-4 genome using the Illumina and PacBio platform. The generated genome was 41.2 Mb in size with a N50 scaffold size of 3.2 Mb, and encoded 10,620 putative predicted genes. A wide spectrum of carbohydrate-active enzymes, with the total number of 341 CAZymes, involved in lignocellulose degradation were identified in H. erinaceus. A total of 447 transcription factors were identified. This present study also characterized genome-wide microsatellites and developed markers in H. erinaceus. A comprehensive microsatellite markers database (HeSSRDb) containing the information of 904 markers was generated. These genomic resources and newly-designed molecular markers would enrich the toolbox for biological and genetic studies in H. erinaceus.
Peripheral nerves have the unique capability to regenerate after injury. Insights into Regeneration of peripheral nerves after injury may have implications for neurodegenerative diseases of the nervous system. We investigated the ability of polysaccharide from Hericium erinaceus Mushroom in the treatment of nerve injury following peroneal nerve crush in Sprague-Dawley rats by daily oral administration. In sensory functional recovery test, the time taken for the rats to withdraw its hind limb from contact with the hot plate was measured. The test revealed acceleration of sensory recovery in the polysaccharide group compared to negative controls. Further, peripheral nerve injury leads to changes at the remotely located DRG containing cell bodies of sensory neurons. Immunofluorescence studies showed that Akt and p38 MAPK were expressed in DRG and strongly upregulated in polysaccharide group after peripheral nerve injury. The intensity of endothelial cells antigen-1 that recognized endothelial cells in the blood vessels of distal segments in crushed nerves was significantly higher in the treated groups than in the negative control group. Our findings suggest that H. erinaceus is capable of accelerating sensory functional recovery after peripheral nerve injury and the effect involves the activation of protein kinase signaling pathways and restoration of blood-nerve barrier.
Hericium erinaceus (Bull.: Fr.) Pers., a Medicinal Mushroom, activates peripheral nerve Regeneration
Conclusion: H. erinaceus is capable of promoting peripheral nerve Regeneration after injury. potential signaling pathways include Akt, MAPK, c-Jun, and c-Fos, and protein synthesis have been shown to be involved in its action.
Hericium flagellum
Basidiomycetes of the genus Hericium are among the most praised Medicinal and edible Mushrooms, which are known to produce secondary metabolites with the potential to treat neurodegenerative diseases. This activity has been attributed to the discovery of various terpenoids that can stimulate the production of nerve growth factor (NGF) or (as established more recently) brain-derived neurotrophic factor (BDNF) in cell-based bioassays. The present study reports on the metabolite profiles of a Lion’s Mane Mushroom (Hericium erinaceus) strain and a strain of the rare species, Hericium flagellum (synonym H. alpestre). While we observed highly similar metabolite profiles between the two strains that were examined, we isolated two previously undescribed metabolites, given the trivial names erinacines Z1 and Z2. Their chemical structures were elucidated by means of nuclear magnetic resonance (NMR) spectroscopy and high resolution mass spectrometry. Along with six further, previously identified cyathane diterpenes, the novel erinacines were tested for neurotrophin inducing effects. We found that erinacines act on BDNF, which is a neurotrophic factor that has been reported recently by us to be induced by the corallocins, but as well on NGF expression, which is consistent with the literature.
Hydnum repandum
FAVOURABLE CULTURE CONDITIONS FOR myceliaL GROWTH OF HYDNUM REPANDUM, A
Medicinal Mushroom
In this study, factors such as pH, temperature, carbon and nitrogen sources that affect mycelial growth of Hydnum repandum, a Medicinal Mushroom, were investigated. Different inoculum media for vegetative inoculum production were also examined. The best suitable pH for mycelial growth was found to be 5.5. Among constant temperatures, the best mycelial growth was obtained at 20 and 25°C. The mycelial growth drastically decreased at 15°C, and no mycelia were obtained at 30°C. glucose and mannitol were found to be the most suitable carbon sources. Ca(NO3)2 as a nitrogen source gave the best Results for mycelial growth. The poorest mycelial growth was noted in sucrose and xylose as carbon sources and in NH4NO3 and (NH4)2HPO4 as nitrogen sources. Peat and peat: vermiculite mixtures (1:4, 1:6, 1:8 and 1:10, v:v) were the best media to use in producing the vegetative inoculum of H. repandum
Hypsizygus marmoreus
organic Mushroom cultivation is one of the fastest growing segments of agriculture. At the core of the organic philosophy lies a ban on the use of synthetic fertilizers, pesticides and herbicides, in addition to such tenets as animal welfare, energy efficiency, and social justice. Hypsizygus marmoreus (HM) is a highly praised cultivated culinary and Medicinal Mushroom. The objective of this paper was to assess the suitability of different spawn media and then the potential of various cultivation substrates to support HM Mushroom production compatible with organic standards. This objective was met through the setup of a low-cost cultivation infrastructure. First, seven types of spawn media were tested; then we tested 24 substrates made from organic by-products for their biological efficiency (BE) with strain HM 830, using the liquid inoculation method. The best substrate in terms of BE was corn cob with bran and olive press cake, with a BE of 85.6%. The BE of the same composition but without olive press cake was only 67.5%. The next best substrates were cotton straw combinations with a BE of 31.5–53%. The spent Mushroom substrate provides a good method for the disposal of solid waste. The guidance provided in this research complies with organic Mushroom cultivation standards and can be used to produce certified organic Mushrooms. In addition, it allows responsible and beneficial disposal of a large amount of solid agro-industrial waste.
Hypholoma lateritium
Conclusion: Organic and water extracts of H. lateritium and compounds 1–6 proved to demonstrate not only considerable inhibitory properties on COX-2, but they are also capable to stimulate the Nrf2 pathway. Our results provide experimental evidence that extracts of Hypholoma lateritium and characteristic compounds of the hexane (6), chloroform (1–5) and more polar (1, 3) fractions possess anti-inflammatory activities, which warrants to be explored in further pharmacological studies.
Imleria badia
Imleria badia culinary–Medicinal Mushroom with interesting biological properties
One of the most popular edible species of wild Mushrooms in many countries is Imleria badia (Fr.) Vizzini. It is a species valued due to its taste, intense aroma after drying and dietary, Medicinal properties. significant amounts of carbohydrates, proteins, polyunsaturated fatty acids and β-tocopherol, but also γ-tocopherol were determined in I. badia fruiting bodies. The presence of low molecular weight organic acids: malic, citric, fumaric and oxalic acids, and phenolic compounds with antioxidant properties, such as p-hydroxybenzoic acid, cinnamic acid and protocatechuic acid, were also found. This species is high in another antioxidant compound – theanine. Recent reports indicated that I. badia fruiting bodies’ extracts showed favorable therapeutic and health-promoting benefits and showed their anti-inflammatory, anti-cancer and antioxidant potential, consisting mainly in an inhibition of lipid peroxidation. Biological properties were also determined and confirmed for mycelium obtained from in vitro cultures of I. badia.
Inonotus baumii
Inonotus baumii, a traditional Medicinal Mushroom, has been historically used in China and other countries of East Asia for the treatment of various diseases. The aim of this study is to investigate the antitumor activity of the extract of I. baumii (EIB) against hepatocellular carcinoma and the possible mechanism involved. The MTT assay was used to evaluate the proliferative activity of SMMC-7721 cells treated with EIB. Hoechst 33258 and JC-1 staining were used to determine nuclear morphological changes and mitochondrial membrane potential, respectively. Flow cytometry analysis indicated that EIB blocked the cell cycle at the S phase and induced significant apoptosis. EIB increased the protein expression of Bax, cytochrome c, cleaved caspase-3, and decreased Bcl-2 in SMMC-7721. Moreover, EIB induced autophagy, indicated by the increase of autophagy-related protein expression of LC3-II and decrease of p62, and the AMPK/mTOR/ULK1 pathway was involved in the autophagic cell death. In vivo, EIB was found to strongly inhibit the growth of tumors in BALB/c nude mice. Our Results indicated that I. baumii might be a potential natural therapeutic agent for liver cancer, as it could induce apoptosis and autophagy in HCC cells.
Inonotus hispidus
antioxidant Hispidin Derivatives from Medicinal Mushroom Inonotus
hispidus
Two natural antioxidants, named inonotusin A (1) and B (2), were isolated from the methanolic extract of the fruit bodies of Inonotus hispidus, together with (E)-4-(3,4-dihydroxyphenyl)but-3-en-2-one (3), hispidin (4) and 3,4-dihydroxybenzaldehyde (5). Their structures were identified by means of extensive NMR and MS data analysis. compounds 1, 2 and 4 exhibited significant scavenging activity against the 2,20-azinobis(3-ethylbenzhi- azoline-6-sulfonate) (ABTS) radical cation. Compound 1 also showed moderate cytotoxicity against a human breast carcinoma cell line (MCF-7) with IC 50 values of 19.6 mmM.
Inonotus linteus
Sesquiterpenes from an Eastern African Medicinal
Mushroom Belonging to the Genus Sanghuangporus.
Inonotus obliquus
New antioxidant polyphenols from the Medicinal Mushroom Inonotus obliquus
The fruiting body of Inonotus obliquus, a Medicinal Mushroom called chaga, has been used as a traditional medicine for cancer treatment. Although this Mushroom has been known to exhibit potent antioxidant activity, the mechanisms responsible for this activity remain unknown. In our investigation for free radical scavengers from the methanolic extract of this Mushroom, inonoblins A (1), B (2), and C (3) were isolated along with the known compounds, phelligridins D (4), E (5), and