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The Chemistry, Nutritional Value, Immunopharmacology, and Safety of the Traditional Food of Medicinal Split-Gill Fugus Schizophyllum commune Fr.:Fr. (Schizophyllaceae). A Literature Review
Abstract
The cosmopolitan wood-loving mushroom, Schizophyllum commune, is used as a traditional food throughout Southeast Asia and India. Researchers have intensively studied a (1→3)-β-D-glucan from the mycelium extract, schizophyllan (SPG) since the 1970s, and today it is used as a biological response modifier (BRM) in combination with chemo- and radiation therapy, especially for cervical and gastric cancers. Based on an abundance of preliminary evidence showing binding of its (1→3)-β-D-glucan to dectin-1 receptors of macrophages and other cells, activation of a T-cell cascade with subsequent increased production of cytokines, such as interleukins and tumor necrosis factor (TNF-α), reduction of tumor size and growth, increased survival of tumor-bearing animals, and a few controlled human trials of varying methodologies and quality, it continues to be used in clinical practice. Larger, well-designed clinical trials are needed to secure its place in modern medical practice in other countries. Fundamental questions such as whether oral application is effective, determination of proper dose, frequency and length of administration, and whether SPG is effective with other types of cancer still need to be answered.
... Alongside tempeh, split gill mushroom is also well known as edible mushroom, having significant nutritional values, incredibly high fiber, protein, and low lipid (Hobbs, 2005), including phenolic compounds in its ethanolic extract (Saetang et al., 2022;Yelithao et al., 2019)). It is a medicinal mushroom with various biological properties (Klaus et al., 2011), for instance, antioxidant, anti-inflammatory, immune-enhancing, anticancer (Patel and Goyal, 2012;Saetang et al., 2022;Wongaem et al., 2021), antiviral and antifungal capacity (Hobbs, 2005). ...
... Alongside tempeh, split gill mushroom is also well known as edible mushroom, having significant nutritional values, incredibly high fiber, protein, and low lipid (Hobbs, 2005), including phenolic compounds in its ethanolic extract (Saetang et al., 2022;Yelithao et al., 2019)). It is a medicinal mushroom with various biological properties (Klaus et al., 2011), for instance, antioxidant, anti-inflammatory, immune-enhancing, anticancer (Patel and Goyal, 2012;Saetang et al., 2022;Wongaem et al., 2021), antiviral and antifungal capacity (Hobbs, 2005). Moreover, the schizophyllan, a polysaccharide derived from split gill mushroom plays a key role in migrating oxidative stress by protecting the human body from free radical-induced damage (Yelithao et al., 2019). ...
... Moreover, the schizophyllan, a polysaccharide derived from split gill mushroom plays a key role in migrating oxidative stress by protecting the human body from free radical-induced damage (Yelithao et al., 2019). Split gill mushroom demonstrates a wide range of industrial application, being utilized in traditional food products (Hobbs, 2005), functional foods (Smirnou et al., 2017), pharmaceuticals (Lee and Ki, 2020), vaccine development, and cosmetic formulation (Smirnou et al., 2017). Given these versatile properties, the study aimed to access the antioxidant potential and inhibitory activities of tempeh and split gill mushrooms in various herbal sausage formulations, contributing to the development of functional meat alternatives. ...
Tempeh, recognized as a high-protein meat alternative, is gaining popularity across Asian countries, while split gill mushroom (Schizophyllum commune), rich in essential nutrients, are increasingly consumed in Southeast Asia. The antioxidant activities of all treatments were significantly higher than the control (p<0.05). Furthermore, formulations containing split gill mushroom (R3, R4, and R5) exhibited lower initial total plate count (TPC) values compared to the other formulations. Sensory evaluation was then conducted on sausages containing tempeh, split gill mushrooms, and their combinations in ratios of 1:1, 1:3, and 3:1, yielding overall acceptance scores of 3.93, 3.30, 4.27, 5.33, and 3.37, respectively. The combination with a 3:1 tempeh-to-mushroom ratio demonstrated the highest consumer acceptance. Therefore, the study on the application of tempeh and split gill mushroom extracts in herbal fresh sausage is provided valuable information for developing plant-based products and functional foods in the future.
... In one of the earlier published literature data, Hobbs (2005) presented that S. commune contain minerals in the followed concentrations: P (408 mg/100 g), Mg (227 mg/100 g), Ca (188 mg/100 g), Fe (12.3 mg/100 g), Zn (5.7 mg/100 g), Cu (0.9 mg/100 g), and Cr (133 μg/100 g). Two years later, Okwulehie et al. (2007) reported the presence of five minerals in S. commune, with N and Ca in the similar concentrations (1.540 mg/100 g d.w. and 1.501 mg/100 g d.w., respectively), followed by Mg, Na and P (0.730 mg/100 g d.w., 0.375 mg/100 g d.w., and 0.145 mg/100 g d.w., respectively). ...
... Let's take a closer look at the schizophyllan (SPG): the most widely researched glucan from S. commune is a water-soluble triple-stranded helix known as schizophyllan, or it is known also with various trade names SPG, sizofiran, sonifilan, and sizofilan (Hobbs 2005). SPG was discovered for the first time by Kikumoto et al. (1970Kikumoto et al. ( , 1971, by the fermentation from S. commune ATCC 38548; it should be noted that the fermentation conditions can be a critical step in the development of economically viable bioprocesses (Garcia et al. 2022). ...
... In a water culture medium S. commune produced a biopolymer hydrophobin with a molecular weight of 24 kDa, and one other protein with molecular weight of 17 kDa (Hobbs 2005). Hydrophobins are known as low molecular weight proteins composed of eight conserved cysteine residues, with a typical hydropathic pattern that affects the hydrophobicity of surfaces by self-assembly at hydrophilic/hydrophobic interfaces (Hobbs 2005). ...
Schizophyllum commune Fr.- SCHIZOPHYLLACEAE
Yusufjon Gafforov, Milena Rašeta, Manzura Yarasheva, Lorenzo Pecoraro, Michal Tomšovský, Chunying Deng, Christopher Hobbs et Sylvie Rapior.
Schizophyllum commune Fr.- SCHIZOPHYLLACEAE. Pages 1417-1443. doi:10.1007/978-3-031-23031-8_124 ; hal-04373908v1 ; hal-04385194v1
... It grows on the dead, fallen, or standing wood of broadleaved trees. Its characteristic is dense white hairs, no stalks, and pale yellow to brown gills (Hobbs, 2005). Cell wall composition is composed of β-glucans cross-linked with chitin (Leung et al., 2006), and the conformation of β-glucans in the mushroom (schizophyllan) is a triple-stranded helix. ...
... Furthermore, there are significant nutritional values, incredibly high fiber, protein, and low lipid (Hobbs, 2005), including phenolic compounds in its ethanolic extract (Yelithao et al., 2019;Saetang et al., 2022c). It is a medicinal mushroom with various biological properties (Klaus et al., 2011), for instance, antioxidant, anti-inflammatory, immune-enhancing, anticancer (Chandrawanshi et al., 2017Du et al., 2017;Smirnou et al., 2017;Yelithao et al., 2019;Lee and Ki, 2020), antiviral and antifungal properties (Hobbs, 2005). ...
... Furthermore, there are significant nutritional values, incredibly high fiber, protein, and low lipid (Hobbs, 2005), including phenolic compounds in its ethanolic extract (Yelithao et al., 2019;Saetang et al., 2022c). It is a medicinal mushroom with various biological properties (Klaus et al., 2011), for instance, antioxidant, anti-inflammatory, immune-enhancing, anticancer (Chandrawanshi et al., 2017Du et al., 2017;Smirnou et al., 2017;Yelithao et al., 2019;Lee and Ki, 2020), antiviral and antifungal properties (Hobbs, 2005). In addition, the schizophyllan plays the leading role in preventing oxidative damage in the human body against free radicals (Yelithao et al., 2019). ...
The nutritional value of routinely used synthetic antioxidants is being reemphasized in today's preventative medicine and food sector. The split gill mushroom is a pharmaceutical mushroom distinguished by its high nutritional content and biological activity. It contains schizophyllan and a polysaccharide made up of β-glucan. The β-glucan has a significant level of antioxidant activity. Therefore, this is an investigation into producing split gill mushroom essence rich in bioactive components. This study examined the total phenolic content and antioxidant capacity (radical scavenging activity) of the schizophyllan (the hot water combined with ethanolic extraction of polysaccharide), supernatant from the separation of the extraction of the polysaccharide, and the mushroom essence (the production of split gill mushroom essence steamed in an electric pressure cooker). From this research, split gill mushroom essence (using an electric pressure cooker) showed more great total phenolic content (14.07 mg of gallic acid equivalent [GAE]/g of dry extract) compared to the supernatant and ethanolic schizophyllan (12.85 and 6.22 mg of GAE/g of dry extract). Furthermore, this mushroom essence revealed more potential for antioxidant activity (IC50 value) for inhibition of free radical (0.73 mg of dry extract/ml), compared to other extracts (IC50 values of the supernatant and the schizophyllan extract as 0.76 and 2.64 mg of dry extract/ml). Therefore, split gill mushroom essence is probably developed as an innovative antioxidant functional food product with beneficial compounds to human health.
... This mushroom grows on a broadleaved tree, dead, fallen, or standing wood. It is distinguished by light yellow to brown gills, dense white hairs, and the absence of stalks [5]. The mushroom composes of β-glucans cross-linked with chitin in its cell wall [6]. ...
... Additionally, this mushroom contains peptides formed during protein hydrolysis by a protease enzyme that exhibits antioxidant properties [13], hydrophobin protein with anticancer activity in S180 mouse sarcoma and B16-F10 mouse melanoma [14], lectin protein with inhibition of cancer cell growth and proliferation [15], both hydrophobin and lectin protein via possibly immunomodulatory [14,16], and schizolysin (hemolysin) with antiviral activity due to inhibition of HIV-1 reverse transcriptase [15]. Besides, this mushroom is abundant schizophyllan, which is distinguished by a variety of biological properties [8], for instance, antioxidant [4,17], anti-inflammatory [7,18], immunomodulatory in immune cells from whole human blood [19] and macrophage cells [4], anticancer activity in lung, gastric, cervical, breast carcinoma cells [20] and tumor-bearing mouse [21], antiviral, antifungal [5], along with prebiotic properties [22]. ...
... Aside from that, β-glucan has a critical role in protecting the body from the oxidative damage caused by free radicals [4]. As a result, the mushroom is used in a wide variety of industrial applications, including pharmaceuticals [7], vaccines, cosmetics, functional food [19][20][21], and traditional food widely in Southeast Asia and India [5]. In addition, β-glucan is a prebiotic oligosaccharide or polysaccharide indigestible in the human digestive system [23]. ...
Schizophyllum commune or split gill mushroom is a pharmaceutical mushroom. Its cell wall contains abundant schizophyllan (β-glucan or polysaccharide from S. commune) distinguished by various biological activities. This experiment focused on studying the optimized ethanol precipitation process of the schizophyllan on the maximum degree of polymerization (DP), highest total sugar, and optimal reducing sugar concentration using response surface methodology (RSM) on central composite design (CCD). The experimental design examined the factors, including the split gill mushroom content (5–15% w/v) and ethanol concentration (49–74% v/v). From this experiment, it could be concluded that the optimized condition of this cost-effective extraction was the low mushroom content 5–8% (w/v) and optimal ethanol concentration 62–65% (v/v) with the highest DP value around 5, along with efficient immunomodulatory and anticancer effects. Thus, further research will develop the pharmaceutical schizophyllan extract as nutraceutical products or drugs.
... This mushroom grows on a broadleaved tree, dead, fallen, or standing wood. It is distinguished by light yellow to brown gills, dense white hairs, and the absence of stalks [4]. The fruiting body is small and fan-shaped with a white spore. ...
... Furthermore, the split gill mushroom is a medicinal mushroom [8] with a variety of nutritional values, including higher phosphorus, magnesium, calcium, iron, zinc, manganese, copper, and chromium, as well as high carbohydrate, fiber, protein, and low lipid, as well as various mineral components, such as higher phosphorus, magnesium, calcium, iron, zinc, manganese, copper, and chromium [4,9]. This mushroom is abundant in schizophyllan, which is distinguished by a variety of biological properties [8], for instance, antioxidant [3,5], anti-inflammatory [7,10], immunomodulatory [3,11], anticancer activity [12,13], antiviral, and antifungal [4], along with prebiotic properties [14]. ...
... Furthermore, the split gill mushroom is a medicinal mushroom [8] with a variety of nutritional values, including higher phosphorus, magnesium, calcium, iron, zinc, manganese, copper, and chromium, as well as high carbohydrate, fiber, protein, and low lipid, as well as various mineral components, such as higher phosphorus, magnesium, calcium, iron, zinc, manganese, copper, and chromium [4,9]. This mushroom is abundant in schizophyllan, which is distinguished by a variety of biological properties [8], for instance, antioxidant [3,5], anti-inflammatory [7,10], immunomodulatory [3,11], anticancer activity [12,13], antiviral, and antifungal [4], along with prebiotic properties [14]. As a result, the mushroom is used in a wide variety of industrial applications, including pharmaceuticals [7], vaccines, cosmetic, functional food [11][12][13], and traditional food widely in Southeast Asia and India [4]. ...
The split gill mushroom or Schizophyllum commune (S. commune) is a therapeutic mushroom. For cell wall composition, it consists of rich β-glucans (schizophyllan). This mushroom is high in nutritional content and has a wide range of biological properties. In this research, it is interesting to study hot water extraction of this functional schizophyllan. Central composite design (CCD) of response surface methodology (RSM) was applied to optimize these extraction parameters, namely, temperature (80-121 °C) and time (1-3 h) of schizophyllan extract (polysaccharide from S. commune) with a greater degree of polymerization (DP), maximum total sugar content, minimum reducing sugar content, and appropriate extraction yield. The results revealed the highest yield obtained from polysaccharide and supernatant extract (from the separation of poly-saccharide extraction) at an extraction temperature of 121 °C for 2-3 h. Moreover, the optimal extraction temperature and time of polysaccharide extracts were 106.5 °C and 126.7 min (total sugar content); 103.1 °C and 177.0 min (reducing sugar content); and 104.1 °C and 175.5 min (DP value). This research shows that the optimum condition of schizophyllan extraction was around 100-110 °C for 2-3 h with the highest DP of about 6, including potential immune-enhancing and anticancer properties. As a result, the schizophyllan from the split gill mushroom is probably utilized as a functional ingredient with nutraceutical compounds and developed as other high value-added functional food products in further study.
... Mushrooms have widely been appreciated all over the world for their nutritional and medicinal properties (Moore and Chiu 2001;Chang and Miles 2008;Barros et al. 2008;Wasser 2010Wasser , 2011Bandara et al. 2015Bandara et al. , 2017Valverde et al. 2015;de Mattos-Shipley et al. 2016;Chang and Wasser 2017;Gupta et al. 2018). The early civilizations of Greek, Egyptian, Roman, Japanese, and Mexican people prized mushrooms for their therapeutic value (Hobbs 1995;Guzmán 2015). Mushrooms have been used in traditional Chinese medicine (TCM) for more than 3000 years for prevention and treatment of different diseases. ...
... Mushrooms are regarded as gourmet food with high nutritional and dietary values, as well as healthy DSs and myco-pharmaceuticals (Hobbs 2005;Khatun et al. 2012;Glamočlija et al. 2015;Kumar 2015;Sękara et al. 2015;Badalyan et al. 2016;Wu et al. 2016;Atila et al. 2017;Biswas et al. 2017;Gargano et al. 2017;Glamočlija and Soković 2017;Reis et al. 2017;Badalyan and Zambonelli 2019;Phan et al. 2018). Therefore, there is a significant potential to develop mushrooms as nutraceuticals and functional food for human wellness and their bioactive molecules for the production of drugs (Dutta 2013;Degreef et al. 2016;Süfer et al. 2016;Landi et al. 2017). ...
... The nutritional value and health benefits of mushrooms are determined by their chemical composition. Many reports on chemical composition and nutritional value of culinary-medicinal mushrooms belonging to different taxonomic and ecological groups were published (Badalian et al. 1997a;Badalyan and Rapior 1999;Hobbs 2005;Nunes et al. 2012;Palazzolo et al. 2012;Kalač 2013Kalač , 2016Badalyan 2015Badalyan , 2016Da Silva et al. 2015;Adejumo et al. 2015;Teklit 2015;Thongbai et al. 2015;Badalyan 2016;Lalotra et al. 2016;Bandara et al. 2017;Kostic et al. 2017;Taofiq et al. 2017a). Mushrooms contain essential minerals, trace elements, vitamins, high levels of dietary fiber (chitin), proteins, unsaturated fatty acids, and nearly free of cholesterol and can be used for various human diets (Ayaz et al. 2011;Badalyan 2015Badalyan , 2016Lalotra et al. 2016;Landi et al. 2017;Phan et al. 2018). ...
Fungi are considered one of the most diverse, ecologically significant, and economically important organisms on Earth. The edible and medicinal mushrooms have long been known by humans and were used by ancient civilizations not only as valuable food but also as medicines. Mushrooms are producers of high- and low-molecular-weight bioactive compounds (alkaloids, lectins, lipids, peptidoglycans, phenolics, polyketides, polysaccharides, proteins, polysaccharide-protein/peptides, ribosomal and non-ribosomal peptides, steroids, terpenoids, etc.) possessing more than 130 different therapeutic effects (analgesic, antibacterial, antifungal, anti-inflammatory, antioxidant, antiplatelet, antiviral, cytotoxic, hepatoprotective, hypocholesterolemic, hypoglycemic, hypotensive, immunomodulatory, immunosuppressive, mitogenic/regenerative, etc.). The early record of Materia Medica shows evidence of using mushrooms for treatment of different diseases. Mushrooms were widely used in the traditional medicine of many countries around the world and became great resources for modern clinical and pharmacological research. However, the medicinal and biotechnological potential of mushrooms has not been fully investigated. This review discusses recent advances in research on the pharmacological potential of mushrooms and perspectives for their clinical application. _____Key-words:
Bioactive compounds · Clinical application · Ethno-mycopharmacology · Medicinal mushrooms · Pharmacological potential.
... Not only protein, but other responses also showed that split-gill mushroom contained significantly (p < 0.05) higher values on all responses, except for moisture content. Since the split-gill mushroom, Schizophyllum commune, is the most potent and most researched of all medicinal mushrooms, it has a long history of use as medicine in Far Eastern nations [37]. The investigation also showed that fat was undetected in oyster mushroom. ...
... such as immunomodulating actions, antibacterial, antidiabetic, and antioxidant qualities [37,[39][40][41][42]. ...
Elderly people are susceptible to malnutrition due to many factors. An essential public health priority is ensuring that seniors have appropriate nutrition to prevent and treat malnutrition and dehydration as well as fulfilling the nutrition necessity. This study was conducted to utilize selected legumes and mushrooms to develop a high-protein instant soup (HPIS) product that is nutritious and suitable for the consumption of the elderly. Black bean, along with oyster mushroom and split-gill mushrooms, exhibited considerable amounts of protein (19.13 ± 1.13, 2.77 ± 0.09, and 4.65 ± 0.61 g/100 g, respectively), calcium (2308.65 ± 113.07, 640.19 ± 0.80, and 743.89 ± 0.66, respectively), iron (40.84 ± 2.42, 7.31 ± 0.05, and 40.10 ± 2.15, respectively), and zinc (18.06 ± 1.07, 3.87 ± 0.03, and 26.23 ± 0.78, respectively) content, and were incorporated into the HPIS formula. Drum dryer rotation speed significantly affected the HPIS properties. The study on the effect of different rotation speeds (3, 5, 7, and 9 RPM) used during the drying process revealed the use of 7 RPM resulting in the soup product with considerable quality. The optimized HPIS formula, which was supplemented with minerals, was moderately liked (7.1–7.5) by the elderly consumer. The majority of the consumers accepted the product (97 %) and were interested in purchasing the product (91 %) if it was available on the market. Incorporating selected legumes and mushrooms resulted in a soup product containing nutrition conforming to the Thai recommended daily intake (RDI), possessing adequate physicochemical and sensory properties for the consumption of the elderly.
... Fungal glucans like scleroglucan and ganoderan possess antiviral properties against Rubella virus and herpes virus [71]. Schizophyllan boosts immune responses in hepatitis B. virus patients, while lentinan fights influenza and polioviruses [72][73][74]. Notably, lentinan, acidic proteoglucan from G. lucidum, and glucans from G. frondosa and T. versicolor are employed as anti-HIV drugs, enhancing host resistance and reducing toxicity of conventional medications. This antiviral action is believed to involve increased interferon-gamma release and enhanced PBMC proliferation [75,76]. ...
Mushroom polysaccharides, key components of fungal cell walls, exhibit various biological properties and hold significant medicinal and industrial value. These polysaccharides are known for their medicinal properties like antitumor, antioxidant, anticancer, immunomodulatory, and an-tiviral properties. Mushroom polysaccharides, particularly β-glucans, α-glucans, and chitin, have been associated with various health benefits. β-glucans are well studied for their bioactivities, while α-glucans and chitin have gained attention for their prebiotic, antimicrobial, and wound-healing properties. The therapeutic effects of these polysaccharides are closely linked to their chemical structures , including molecular weight, monosaccharide composition, and glycosidic bond types. This work aims to review the studies on mushroom polysaccharides, with a particular focus on their structural composition to deepen medicinal properties of mushroom polysaccharides. Also, the extraction methods and the pharmaceutical application of polysaccharides will be revised in this work.
... Activation of T cell, increase interleukin, and TNF-a production, Radical scavenging activity, ferric ion reducing power [48][49][50] Pleurotan ...
Microbial polysaccharides are the water soluble renewable biopolymers which comprise a variety of polysaccharides produced by bacteria, fungi and yeast. These microbial polysaccharides have unusual molecular structure and peculiar conformations rendering them with unique and potentially interesting properties. In recent years, demand of natural polymers for various industrial applications has led to an increased attention towards production of microbial polysaccharides. Since the microbial origin polysaccharides have properties identical to the currently used gums they have been widely used as an alternative in various food, pharmaceutical, and cosmeceutical industries as emulsifiers, binders, gelling agents and suspending agents. There has been an increase in the adoption of microbially sourced polysaccharides and this surge in demand has resulted in the manufacturers to now focus on enhancing their production capacity. The current review deals with the worldwide commercial utilization of the microbial polysaccharides and their present status in the polysaccharide market.
... Schizophyllum commune, also known as "split fold," is a medicinal mushroom. This mushroom's habitat is primarily in light, sunny, dry areas of the forest, with a texture that is small, thin, flexible, whitish in colour and grown in layers that overlap on each other (Hobbs, 2005). S. commune mushroom having four bioactive compounds consisting antimicrobial activity namely methanol, dichloromethane, ethyl acetate and water against B. cereus, B. subtilis, E. faecalis, S. aureus, P. shigelloides, P. aeruginosa, P. vulgaris, Salmonella sp. ...
Nowadays, multidrug antimicrobial resistance is a very common issue globally. Antimicrobial resistance is fueling the fire, and it has been noted that infectious disease incidence and deaths are rising throughout the world. Many pathogens have been reported to develop resistance to these synthetic and semi-synthetic drugs leading to minimized efficacy and resulting in substantial economic losses all over the world. A new approach for choosing natural extracts of plants and fungi as medicines and natural antibacterial agents has been developed to address this challenge. According to recent investigations and research, mushrooms and their extracts contain bioactive compounds that can be used as a natural antibacterial alternative against a number of bacterial species. In addition to having medical properties like antibacterial, anticancer, and antioxidant activity, mushrooms are a highly nutritious food source. The present study emphasized on the antimicrobial resistance, mechanisms and antibacterial properties of mushrooms.
... Europe and North America AT, AO, AV, HC, HG, AB, AA, AP, PP [145] Agaricus blazei Brazil, China and Japan AS, HP, HL, AD, DER, AT, IST [146,147] Auricularia auricula-judae China and Australia AO, AT, HOL, ACO, IMD [148] Auricularia polytricha India and China AT, AHC [149,150] Boletus edulis Europe, Asia, North America, South Africa, Australia, New Zealand, and Brazil AN, AO [151,152] Calvatia gigantea Britain, Ireland, and North America AO, AT, ABI, AV, AB [153,154] Cantharellus cibarius France, Britain and India HP, AM, AO, AHS, AI, NP [155,156] Cortinarius caperatus Northern regions of Europe and North America. AF, AO, AV [157] Craterellus cornucopioides North America, Europe, Japan, and Korea AO, AHG, AI, AM, IMD [158,159] Craterellus tubaeformis Northern America, Europe, and Asia AI, AO [160,161] Flammulina velutipes China, Japan, Korea, and Taiwan AO, AC, AHT, AM, IMD, HP [162,163] Ganoderma lucidum Malaysia, China, Japan and South Korea AO, AT, AAN, CP [164] Grifola frondosa Japan, China Europe and North America AO, AD, AT, IMD, AM, HP [165] Hericium erinaceus Britain, Europe, central and southern France, North America ACG, ABI, AD, AFT, AHT, AHL, CP, HP, NFP, NP [166,167] Hypsizygus tessellatus Europe, North America and Australia AO, AI, AAL, AT, AB, AF, AO, IMD [168,169] Lentinula edodes Asia, China and Japan AF, AB, AT, CYT, APO, AO [170,171] Lactarius deliciosus Europe, North America, Central America, Australia, and New Zealand AB, AF, CYT, AI, INS, NMT, AO, AT, IMD [134,172] Morchella esculenta North America, North Canada, and India AO, IMD, AT, AF, HP [173,174] Phellinus linteus Japan, China, Korea and India AI, AT, IMD, AD, AF [175] Phellinus rimosus Eastern and North America AO, AI, NP, AHET [176] Pleurotus eryngii Europe, West Asia and North Africa TP, AT, AM [22] Piptoporus betulinus Europe, North America and Asia AV, AT, CUSH [177,178] Pleurotus ostreatus/ Pleurotus pulmonaris Worldwide IMD, AT, AHG, AO, AV, AB, AF [179] Russula delica Europe and Asia AI, AO, AP, AV [180] Schizophyllum commune Northeast India AT, IMD, AO, AF, APL, AV [181,182] ...
Mushrooms have been an acclaimed food for their unique flavor and medicinal properties since ancient times. Modern research shows that mushrooms are rich in various nutrients and biologically active substances. In recent years, researchers have become increasingly interested in mushrooms because they contain important secondary metabolites, such as phenolic compounds with significant bioactive properties. This review introduces the nutritional components and secondary metabolites in mushrooms, focusing on the bioactive functions and potential applications of mushroom polyphenols. Finally, the current challenges and future research trends of mushroom polyphenols are briefly discussed. In the aspect of nutritional value, mushrooms are high in protein and insoluble fiber, while low in fat and sodium, making them a low-energy, healthy food. Mushrooms contain a large amount of beneficial bioactive substances for health, including phenolic compounds, as well as tocopherols, terpenoids, and phytosterols. Mushroom polyphenols have antioxidant, anti-inflammatory, anti-cancer, anti-tyrosine, antihyperglycemic, and other biological activities beneficial to human health and medical applications, especially in the various degenerative disease and cancer treatments. However, based on the properties of phenolic compounds, research and development in commercial applications still face many issues that need to be addressed by researchers.
... The generic name 'Schizophyllum' simply means 'split leaves' while the specific epithet 'commune' meaning 'common or communal' -means share (as it is shared all over the world). It produces schizophyllan which is used to treat cervical and gastric cancers as a biological response modifier (BRM) in combination with chemotherapy and radiation therapy (Hobbs, 2005). This polysachharide has been used in pharmaceutical sector for its immunomodulatory, antineoplastic, and antiviral effects, which are stronger than those of other glucans. ...
The book is a photographic field guide on wild-edible, inedible, medicinal and poisonous mushrooms of Mizoram compiled from a collection of more than 300 specimens accumulated over a span of 5 years. It contains 81 species of mushrooms (including 13 genus-level identified species) belonging to 50 genera of 30 families. It provides visual and written directories on a vast variety of fungi across the state to aid farmers, consumers, research scholars, mycologists, agri-horti personnels and laymen in verifying important characteristics of wild mushrooms. The book also emphasizes the ways and means of mushroom collection and preservation along with significant identification patterns. It includes local names in Mizo language for easier classification along with ethnomycological detail and uses for promoting the wide scope and significance of wild mushroom foraging among the locals. The book is anticipated to be an essential step towards eradicating mycophobia and unfortunate misidentifications.
... SSF represents an artificial simulation of the growth of fungal cells that can be used to produce enzymes, ethanol, organic acids, and vitamin products, and it is one of the most common methods in the food industry. The SSF technology threshold has strong development potential due to its low energy requirements and low infrastructure investment [44]. In previous pharmacological studies, SC was also demonstrated to suppress cytokine production (interferon-γ, tumor necrosis factor-α, interleukin (IL)-1β, IL-6, IL-8, and IL-10) in dengue-infected human monocytes infected with dengue virus-2 (DENV-2) New guinea C strain [43], regulate immune responses in chronic hepatitis B patients [45], and scavenge free radicals [46]. ...
The current global pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) of COVID-19 has infected hundreds of millions of people, killed millions, and continues to pose a threat. It has become one of the largest epidemics in human history, causing enormous damage to people’s lives and economies in the whole world. However, there are still many uncertainties and continued attention to the impact of SARS-CoV-2 on human health. The entry of SARS-CoV-2 into host cells is facilitated by the binding of the spike protein on the virus surface to the cell surface receptor angiotensin-converting enzyme 2 (ACE2). Furthermore, transmembrane protease serine 2 (TMPRSS2) is a host surface protease that cleaves and proteolytically activates its S protein, which is necessary for viral infection. Thus, SARS-CoV-2 uses the ACE2 receptor for cell entry and initiates the S protein using the protease TMPRSS2. Schizophyllum commune (SC) is one of the most widely distributed fungi, often found on the rotten wood of trees that has been found to have various health benefits, including anticancer, antimicrobial activity, antiparasitic, and immunomodulatory function. In this article, SC significantly diminished the expression ACE2 and TMPRSS2 protein in vitro and in vivo without cell damage. In addition, adenosine from SC was also proven in this experiment to reduce the ACE2 and TMPRSS2 expression. Thus, our findings suggest that SC and adenosine exhibit potential for the repression of SARS-CoV-2 infection via the ACE2 and TMPRSS2 axis.
... Trametes versicolor (L.) Lloyd and β-(1-6) -d-glucan from A. subrufescens (Ikekawa et al. 2001;Hobbs et al. 2005;Angeli et al. 2009;Yao et al. 2011;Ziaja-Sołtys et al. 2020). Studies on fungal polysaccharides at this concern are mostly focused on their immunomodulant properties (Chakraborty et al. 2019); lentinan in particular is a model since it stimulates immune response and it is also applied in creams for external use (Bisen et al. 2010). ...
Medicinal mushrooms are a rich source of bioactive molecules, nutraceutic products, as well as natural co-formulants and excipients. The fungal cell wall is rich in branched polysaccharides (mainly β-glucans), peptidic residues, and chitin or chitosan. A plethora of secondary metabolites with current or potential application includes e.g. terpenoids, polyketides, ceramides, polyphenolics, l-ergothioneine and others.Mushroom application in cosmetics has been explored for a few decades only, but the increasing demand for bio-based products has stimulated this research field. Strategies against skin aging are the main target of cosmetic
and cosmeceutic applications. Based on an integrated approach that pursues psycho-physical wellness, Systemic Aesthetic Medicine focuses on both external (creams, lotions) and internal (food
supplements) uses of fungal molecules and extracts, besides the introduction in the diet of bulk fungal biomass (nutritional strategy). Far beyond the pure cosmetology, Systemic Aesthetic Medicine in fact focuses on prevention and treatment of skin diseases and cutaneous symptoms. Main properties reported from mushrooms at this concern include: hydration, anti-oxidant, acceleration of skin cells turnover, stimulation of skin bio-reparation, antiseptic, and immunomodulant.KeywordsMedicinal mushroomsSkinSystemic aesthetic medicineCosmeticCosmeceutic
... In preliminary clinical trials, increases in body weight, CD4 cell counts and haemoglobin levels were observed in HIV/AIDS patients administered powdered material extracted from Ganoderma mushrooms [49]. Biologically active polysaccharides are particularly effective in retarding the progress of various cancers and other diseases (through immune stimulation rather than direct cytocidal effects), and in alleviating the side effects of chemotherapy and radiation treatment (through cell-level regenerative effects) [50,51]. In general, high Fomes fomentarius Antitumour, immuno-stimulatory and antiinflammatory. ...
The survival of Homo sapiens is continually under threat from agencies capable of inflicting calamitous damage to the overall health and well-being of humankind. One strategy aimed at combatting this threat is focused on medicinal mushrooms and derivatives thereof. Mushrooms themselves have been consumed as part of the human diet for centuries, whereas 'mushroom nutriceuticals' is a more recently adopted term describing mushroom-derived products taken as dietary supplements to enhance general health and fitness. Among the most extensively studied pharmacologically active components of mushrooms are polysaccharides and polysaccharide-protein complexes, triterpenes, lectins, and fungal immunomodulatory proteins. Medicinal mushrooms have been credited with a wide range of therapeutic properties including antitumour/anti-cancer, antioxidant, hepatoprotective, anti-diabetic, antimicrobial, cholesterol-lowering and genoprotective activities as well as protection against atherosclerosis, cardiovascular, chronic inflammatory and autoimmune diseases, and neurodegenerative conditions. This review examines the past, present and future of medicinal mushroom development including the two legs concept for the mushroom industry and the pyramid model summarizing the various human applications of mushrooms. It considers numerous issues the industry needs to address to exploit fully the opportunities presented by the continued increasing demand for medicinal mushrooms, and by the future overall expansion of the medicinal mushroom movement.
... It grows on the broadleaved trees, standing, dead, or fallen woods. Its characteristic has pale yellow to brown gills, dense white hairs, and an absence of stalks (Hobbs, 2005). Additionally, this mushroom is a medicinal mushroom (Klaus et al., 2011) with abundant nutritional values, especially in terms of high carbohydrate, protein, and low lipid (Basso et al., 2020). ...
Schizophyllum commune (split gill mushroom) is the alternative protein source. This mushroom comprises of nutritive mycoprotein (mushroom protein) with essential amino acids, including pharmaceutical schizophyllan (β-glucan), and so on. It also has plentiful nutritional values and various biological properties. This research focused on studying the influence of hot water treatment on this alternative mycoprotein. The factorial experiment in complete randomized design (CRD) was applied to investigate these response variables, namely temperature (80-121°C) and time (1-3 hr) of hot water extraction of mycoprotein. This experiment noticed that the maximum protein content (10.47 mg/g extract) was obtained from 80°C and 1 hr extraction temperatures. However, in order to extract the schizophyllan with biologically pharmaceutical activities, the optimized extraction conditions of the polysaccharide extracts were around 100°C for 2 hr with the highest degree of polymerization (DP value about 6), along with immunomodulatory and anticancer properties. However, the protein content of this extract was not greater (7.10 mg/g extract) due to the denaturation of some protein at a higher extraction temperature. Therefore, the actual commercial extraction of bioactive mycoprotein should consider both lower extraction temperature to sustain this mycoprotein's nutritional and pharmaceutical values, including the optimal yield of the protein extract. Additionally, the mycoprotein extract from S. commune is probably utilized as an alternative protein ingredient in functional food, snack or beverage products in further study.
... It was noted that most of the fungal medicinal substances exhibiting antitumour activity belong to the groups of β-glucans and β-glucan-protein complexes. It is interesting to note that β-glucan-protein complexes demonstrate higher immunostimulatory activity than free glucans [24,28,33,37,[79][80][81][82][83][84][85][86][87][88][89][90][91]. Therefore, our research was aimed at characterization and evaluated the cytotoxicity of protein fractions of vegetative mycelium of medicinal basidiomycete L. edodes on cancer cell lines. ...
Detection and study of biologically active compounds seems a promising area of research in cancer diagnostics and therapies. The glycoprotein and polysaccharide fractions showing high cytotoxicity towards several human and animal cancer cell lines: A549, Hep-2, HeLa, С6 and SPEV-2 were isolated from basidiomycete Lentinus edodes vegetative mycelium and fruiting body and further characterized. It was found that water-soluble glycoprotein fractions caused the most significant, 70–100% inhibition of metabolic activity of SPЕV-2, А549 and С6 cell lines. The effective concentrations of glycoprotein fractions reducing the viability of cancer cell lines were determined. The protein and subunit composition of fractions was studied; the highly active galactose-specific lectins were found to be present in these fractions. Comparative analysis of transcriptomes of L. edodes vegetative mycelium, fruiting body and primordium revealed the presence of carbohydrate-binding glycoproteins (lectins) specific for each stage of basidiomycete morphogenesis. Histological examination revealed some morphological indicators of immune system activation and the absence of toxic effect on gastro-intestinal mucosa of animals at peroral administration of fungal glycoprotein fractions. Fungal protein and, in particular, lectin preparations derived from L. еdodes vegetative mycelium might be considered as novel prospective tools in cancer diagnostics and therapies.
... Mushrooms are considered to be repertoire of complex polysaccharides, proteins, lesser fat and other nutritional factors. The results of this study show that S. commune despite being a wild growing fungi is rich in nutrients containing 46% carbohydrate, 26% protein, 1.32% fat which has been agreed by the studies of Demirbas (2001); Latiff et al. (1996);Hobbs (2005) who found that usually, the mushroom fruiting bodies, contain about 39.9% carbohydrate, 17.5% protein and 2.9% fats on a dry weight basis. The fibre, ash and moisture content of S. commune in this study are in agreement with Okwulehie et al. (2007). ...
The common split-gilled mushroom, Schizophyllum commune Fr., is an edible medicinal mushroom found growing on wood under natural conditions across the globe. The present study was carried out to investigate the morphological and anatomical features of the basidiocarp and the cultural characteristics of S. commune along with identification of locally available agricultural residues as a potential substrate for large scale production of the mushroom. The morphology of S. commune revealed it as a split-gilled white fungus with flabelliform basidiocarp. The polypore was identified as trimitic in nature with thin walled generative, skeletal and binding hyphae bearing septa and clamp connections. A potato dextrose agar (PDA) culture from the fruiting body yielded a rapidly growing white woolly mould. S. commune was confirmed by sequence analysis of the internal transcribed spacer region. The mushroom seed or spawns were produced by growing the mycelium on paddy grains with complete white cotton mycelial growth and a characteristic tart and disagreeable smell. The commercial cultivation technology of S. commune was standardized on paddy, wheat straw and saw dust bag logs at 28 ± 2 • C and 80-90% relative humidity. The cultivation trial recorded paddy straw supplemented with wheat bran as the best substrate for growing of S. commune with highest fresh weight yield of 91.9 gm/bag, and biological efficiency of 18.33%, reduced spawn run days and days to harvesting.
... Mushrooms are considered to be repertoire of complex polysaccharides, proteins, lesser fat and other nutritional factors. The results of this study show that S. commune despite being a wild growing fungi is rich in nutrients containing 46% carbohydrate, 26% protein, 1.32% fat which has been agreed by the studies of Demirbas (2001); Latiff et al. (1996);Hobbs (2005) who found that usually, the mushroom fruiting bodies, contain about 39.9% carbohydrate, 17.5% protein and 2.9% fats on a dry weight basis. The fibre, ash and moisture content of S. commune in this study are in agreement with Okwulehie et al. (2007). ...
The common split-gilled mushroom, Schizophyllum commune Fr., is an edible medicinal mushroom found growing
on wood under natural conditions across the globe. The present study was carried out to investigate the
morphological and anatomical features of the basidiocarp and the cultural characteristics of S. commune along
with identification of locally available agricultural residues as a potential substrate for large scale production of
the mushroom. The morphology of S. commune revealed it as a split-gilled white fungus with flabelliform
basidiocarp. The polypore was identified as trimitic in nature with thin walled generative, skeletal and binding
hyphae bearing septa and clamp connections. A potato dextrose agar (PDA) culture from the fruiting body
yielded a rapidly growing white woolly mould. S. commune was confirmed by sequence analysis of the internal
transcribed spacer region. The mushroom seed or spawns were produced by growing the mycelium on paddy
grains with complete white cotton mycelial growth and a characteristic tart and disagreeable smell. The com-
mercial cultivation technology of S. commune was standardized on paddy, wheat straw and saw dust bag logs at
28 ± 2◦C and 80–90% relative humidity. The cultivation trial recorded paddy straw supplemented with wheat
bran as the best substrate for growing of S. commune with highest fresh weight yield of 91.9 gm/bag, and bio-
logical efficiency of 18.33%, reduced spawn run days and days to harvesting.
... This fungus produces immunostimulant polysaccharides, schizophyllan or sonifilan ((1 3)-β-D-glucans with ramifications (1 6)β-D-glucosyl) that are widely used for treatment of cervical cancer, mainly in Asian countries Liu 2000, Chang and. In traditional Chinese medicine, S. commune is used in the form of infusions to treat leucorrhoea (Ying et al. 1987, Hobbs 2005, Adejoye et al. 2007, Calonge 2011, Vázquez-Mendoza 2012 and has also been used for regulating blood pressure (Boa 2005). ...
ABSTRACT
In this chapter, we report on the effects of Pleurotus (oyster mushroom) extracts (Myc-E and FB-E) and powders
(FB-P) on immunodeficient BALB/c mice. The anti-proliferative effect on NB4 human leukemia cells was measured
by flow-cytometry. In addition, antioxidant activity was investigated by scavenging of DPPH and ABTS radicals,
reducing power and inhibition of lipid peroxidation. Pleurotus mycelial extract (Myc-E) exerted a protective effect in
both cyclophosphamide and whole-body irradiated mice in terms of bone marrow cellularity, white blood cell counts
and enhancement of the monocyte-macrophage system. Cyclophosphamide treated mice also showed a stimulant
effect on cell immune response when administered with fruiting body powder (FB-P). Fruit body-derived extract
(FB-E) stimulated immunonutritional recovery of malnourished mice after activation of gut-associated lymphoid
tissues. Myc-E reduced viability of NB4 leukemia cells, particularly at a concentration of 200 μg/ml, by arresting
cells in the G2/M phase. At 10 mg/ml, FB-E showed scavenging effects for DPPH and ABTS radicals (90.4% and
80%, respectively) and inhibited lipid peroxidation (51.2%), whereas at 5 mg/ml manifested a reducing power of
0.438. Pleurotus derived-products could be considered good candidates for developing nutraceuticals and innovative
myco-therapeutics, as judged by their immunomodulating/antitumor and antioxidant effects.
... Il β-(1-3)d-glucano con struttura a tripla elica è stato isolato per la prima volta dal corpo fruttifero di Lentinula edodes alla fine degli anni '60 del secolo scorso in Giappone (Ikekawa, 2001). Da allora lo schizofillano di Schizophyllum commune, il lentinano di Lentinus edodes, il PSK legato alle proteine di Coriolus versicolor e il β-(1-6)-d-glucano di Agaricus subrufescens sono stati isolati dalle differenti specie (Hobbs et al., 2005;Yao et al., 2011;Ziaja-Sołtys et al., 2020). Il lentinano è un composto attivo incorporato in creme in grado di stimolare il sistema immunitario, rafforzandone la capacità di combattere infezioni e malattie (Bisen et al., 2010). ...
Nella continua ricerca di nuovi ingredienti funzionali ed efficaci per la cosmesi, lo studio delle attività bio- logiche di varie specie di funghi ha attratto l’atten- zione degli scienziati e delle aziende, in particolare per l’azione antinvecchiamento, ma anche per quelle idratanti e di contrasto dell’acne.
... Schizophyllum commune Schizophyllan, 1,6-monoglucosyl branched β-1, 3-d-glucan Activation of T cell, increases interleukin, and TNF-α production [51] Sparassis crispa β-Glucan Enhances IL-6 and INF-γ production [52] Taiwanofungus camphoratus (syn. Antrodia camphorate) ...
... Schizophyllum commune Schizophyllan, 1,6-monoglucosyl branched β-1, 3-d-glucan Activation of T cell, increases interleukin, and TNF-α production [51] Sparassis crispa β-Glucan Enhances IL-6 and INF-γ production [52] Taiwanofungus camphoratus (syn. Antrodia camphorate) ...
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.
... Mushrooms have been used by various civilizations for at least 7,000 years, especially in China, India, Japan, and Korea, where they have been used as a rich source of nutrients, but also as a part of traditional medicine regimens (Chang, 1999;Hobbs, 2005). Out of about 7,000 edible species, around 800 are known to possess significant pharmacological properties, and these are known as medicinal mushrooms (Boa, 2004;Barceloux, 2008;Wu et al., 2013). ...
Colorectal cancer (CRC) is the third most frequent cancer type in both males and females, with about 35% of patients being diagnosed in stage IV metastatic disease. Despite advancements in treatment, life expectancy in patients with metastatic disease is still not satisfying. Due to frequent drug resistance during conventional and targeted cancer treatments, the development and testing of multi-target therapies is an important research field. Medicinal mushrooms specific isolated compounds as well as complex extract mixtures have been studied in depth, and many mushroom species have been proven to be non-toxic multi-target inhibitors of specific oncogenic pathways, as well as potent immunomodulators. In this study, we have performed a tandem mass tags qualitative and quantitative proteomic analyses of CT26.WT colon cancer tumor tissues from Balb/c mice treated with the studied medicinal mushroom extract mixture, with or without 5-fluorouracil. Besides significantly improved survival, obtained results reveal that Agarikon.1 alone, and in combination with 5-fluorouracil exert their anticancer effects by affecting several fundamental processes important in CRC progression. Bioinformatic analysis of up- and downregulated proteins revealed that ribosomal biogenesis and translation is downregulated in treatment groups, while the unfolded protein response (UPR), lipid metabolism and tricarboxylic acid cycle (TCA) are upregulated. Moreover, we found that many known clinical biomarkers and protein clusters important in CRC progression and prognosis are affected, which are a good basis for an expanded translational study of the herein presented treatment.
... This fungus produces immunostimulant polysaccharides, schizophyllan or sonifilan ((1 3)-β-D-glucans with ramifications (1 6)β-D-glucosyl) that are widely used for treatment of cervical cancer, mainly in Asian countries (Ooi andLiu 2000, Chang andMiles 2004). In traditional Chinese medicine, S. commune is used in the form of infusions to treat leucorrhoea (Ying et al. 1987, Chang and Miles 2004, Hobbs 2005, Adejoye et al. 2007, Calonge 2011, Vázquez-Mendoza 2012 and has also been used for regulating blood pressure (Boa 2005). ...
Cultivation of tropical edible mushrooms has generated an enormous and growing interest because it represents a new alternative for various sectors to produce beneficial food products using environmentally friendly biotechnologies. In particular, the academic sector has prompted development of research to diversify means and techniques of cultivation while also integrating various aspects such as traditional knowledge and use of local genetic resources. In this chapter, data on biology and consumption of Schizophyllum commune Fr. in tropical regions are presented in addition to observations on cultivation of
this fungus under semi-controlled conditions on several agricultural by-products from Tabasco, México.
... Lentinus edodes T-cell-oriented adjuvant [149] PS-G Ganoderma lucidum Activating macrophages and T lymphocytes [135,136] Schizophyllan Schizophyllum commune Activating T cell, increasing interleukin and TNF-α production [150] Terpenoids Exobiopolymers Ganoderma applanatum Activating NK cell [128] Ganolucidoid A and B Ganoderma lucidum NO production, anti-inflammatory activities [130] Lanostane Hypholoma fasciculare NO production, anti-inflammatory activities [151] The fungal immunomodulatory protein FIP-fve that was obtained from Flammulina velutipes has been employed to suppress the respiratory syncytial virus (RSV), which is known to cause bronchiolitis. FIP-fve effectively decreased RSV replication, IL-6 expression, and inflammation via inhibition of NF-κB translocation and respiratory pathogenesis in RSV-challenged mice. ...
The inhibition of viral protease is an important target in antiviral drug discovery and development. To date, protease inhibitor drugs, especially HIV-1 protease inhibitors, have been available for human clinical use in the treatment of coronaviruses. However, these drugs can have adverse side effects and they can become ineffective due to eventual drug resistance. Thus, the search for natural bioactive compounds that were obtained from bio-resources that exert inhibitory capabilities against HIV-1 protease activity is of great interest. Fungi are a source of natural bioactive compounds that offer therapeutic potential in the prevention of viral diseases and for the improvement of human immunomodulation. Here, we made a brief review of the current findings on fungi as producers of protease inhibitors and studies on the relevant candidate fungal bioactive compounds that can offer immunomodulatory activities as potential therapeutic agents of coronaviruses in the future.
... However, the fungal diversity of the humid tropics has not been extensively explored (Guzmán 2008, Acosta-Aguirre et al. 2014, therefore an increase in the Schizophyllum records for this region is to be expected, as this region contains the highest biological richness within the country (Espinoza-Organista et al. 2008) and experiences annual rainfall levels that surpass 2 500 mm (Olvera-Salgado 2010). Furthermore, in the humid tropics and in other regions, at least 50% of Schizophyllum species are edible or have medicinal properties (Ying & Mao 1987, Chang & Miles 2004, Ruán-Soto et al. 2004, Boa 2005, Hobbs 2005, Ruán-Soto et al. 2006, Adejoye et al. 2007, Calonge 2011, Vázquez-Mendoza 2012, Moreno-Fuentes 2014. As a result, biotechnological interest has also been focused on species of this genus and their potential applications (Kumar et al. 2014, Turlo 2014, Horisawa et al. 2015, Siqueira et al. 2016. ...
The genus Schizophyllum is easily recognized within the order Agaricales. However, at the species level, taxonomic information for identification purposes is limited. The objective of the present study was to confirm the identity of the Schizophyllum species present in Tabasco, Mexico, by means of a detailed taxonomic revision of the macro- and micromorphological characters in more than 90 specimens, as well as phylogenetic analyses inferred from ITS sequence data. In total, three Schizophyllum species are described, of which one constitute a new record for Mexico. Finally, the edibility of S. radiatum is reported for the first time in the humid tropical region.
... This fungus produces immunostimulant polysaccharides, schizophyllan or sonifilan ((1 3)-β-D-glucans with ramifications (1 6)β-D-glucosyl) that are widely used for treatment of cervical cancer, mainly in Asian countries Liu 2000, Chang and. In traditional Chinese medicine, S. commune is used in the form of infusions to treat leucorrhoea (Ying et al. 1987, Hobbs 2005, Adejoye et al. 2007, Calonge 2011, Vázquez-Mendoza 2012 and has also been used for regulating blood pressure (Boa 2005). ...
The Tropics is a very large area of the planet Earth with abundant and surprising biodiversity; however, it remains poorly understood. Macromycetes are no exception because they have been little studied. It is this lack of information, the desire to highlight them, and to show that these organisms should and deserve to be further studied, is what led to the publication of this book. Macromycetes are organisms with great potential for humanity as food, medicine and for biotechnological applications. This has been amply demonstrated by the few examples worldwide already studied and exploited today. Certainly, there is in tropical macromycetes an additional interest in conducting research in a poorly explored field that is necessary for better development and benefit of mankind.
In this book, specialists in the field review cultivation techniques for some tropical and subtropical species such as Agaricus subrufescens, Sparassis latifolia, Tremella fuciformis, Schizophyllum commune, Lepista nuda, and some promising biotechnological applications of Auricularia spp., Grifola frondosa, Pleurotus spp., and Volvariella spp. Likewise, the existence of tropical species of Agaricus and Lentinula is highlighted. Undoubtedly, this list is only a small sample of the great diversity of macromycetes present in the tropics.
The aim of this book is to draw attention to some of the research on tropical macromycetes available today. Furthermore, we sought to help motivate researchers, students, professionals and other individuals, to increase interest, and to redouble efforts to confront the enormous -Herculean- task of research that remains.
Hybrid gels combining chicken and mushroom offer innovative functional food choices, catering to the growing demand for flexitarian-friendly products. These gels reduce meat content while enhancing dietary fiber, bioactive compounds, and sustainability. This study examined the effects of split gill mushroom (Schizophyllum commune) powder (SGM) substitution (0%, 25%, 50%, and 75%, w/w) for Ligor chicken meat in hybrid gels, focusing on rheological and gelling properties. The 25% SGM gel demonstrated optimal performance in terms of rheology, texture, microstructure, pH, water-holding capacity, and color. At this level, hybrid gels exhibited superior gelation properties, demonstrating elasticity dominance, as indicated by a higher storage modulus (G′) than loss modulus (G″), along with stable cohesiveness and unaffected springiness (p > 0.05). However, hardness, gumminess, and chewiness were significantly lower than the control (p < 0.05). Higher SGM levels (50–75%) markedly weakened the gels, reducing viscoelasticity, increasing porosity and water release, and causing discoloration. These findings highlight 25% SGM as an optimal level for hybrid meat gels, maintaining product quality while promoting sustainability in the meat industry.
Edible mushrooms constitute a small fraction (about 21%) of the total documented macroscopic species of fungi. A lesser proportion of these nutrient-rich delicacies have been identified to confer therapeutic benefits. Although harvesting from the wild was historically the predominant way of obtaining these mushrooms, commercial cultivation of species such as oyster, giant panus, maitake, and button mushrooms is currently a common practice. Edible mushrooms are gaining pharmaceutical relevance over synthetic drugs due to the proven efficacy and harmless effect of their polysaccharide, protein, phenolic, sterol, terpene, and terpenoid constituents. Numerous studies have reported on the ability of mushroom-derived compounds to prevent and/or remedy ailments that are of global concern. Among these ailments are hypercholesterolemia, hepatotoxicity, and immunodeficiency, which are in one way or another linked to the development of other severe health issues. The naturally derived compounds from edible mushrooms have been demonstrated in several in vivo (animal and clinical) and in vitro investigations to combat the organ and/or organ system dysfunctionality associated with the aforementioned abnormalities. Some of the well-studied examples across the class of bioactive compounds found effective against these conditions include β-glucan, lectins, FIPs, eritadenine, lovastatin, ergosterol, and triterpenoids. This chapter provides detailed information on the activities of bioactive compounds derived from edible mushrooms, emphasizing on their potential as hypocholesterolemic, hepatoprotective, and immunomodulatory agents. The wealth of available information on the emphasized therapeutic effects of these active compounds could potentially serve as a basis for their consideration in the development of pharmacognostic products.
This study analyzes the chemical composition of three medicinal fungal species: Fomes fomentarius, Ganoderma lucidum, and Trametes versicolor, with the aim of examining their mineral content, essential elements, trace elements, macroelements, and pH in order to evaluate their medical and ecological potential. The fungi are rich in bioactive compounds, including polysaccharides, triterpenes, and phenolic compounds, which are being studied for their potential therapeutic properties, such as anticancer, anti-inflammatory, and immunomodulatory effects. Additionally, the presence of essential minerals and trace elements, such as calcium (Ca), magnesium (Mg), iron (Fe), and zinc (Zn), contributes to their nutritional value. The study revealed that the pH values of these fungi vary. Furthermore, the analysis indicated the presence of toxic metals, such as cadmium (Cd), lead (Pb), and mercury (Hg), which may pose health risks if the fungi are consumed or used for medicinal purposes in pharmaceutical preparations. This paper also discusses the potential of these fungifungis within the context of circular bioeconomy and bioremediation, as well as their role in sustainable production and biodiversity conservation. The results suggest that these fungi have a wide range of potential applications, though further research is required to optimize their use in medicine and ecological processes.
Amaç: Mikoterapi, Geleneksel ve Tamamlayıcı Tıp (GETAT) uygulamaları kapsamında tıbbi mantarların adjuvan tedavi yöntemi olarak kullanılması olarak tanımlanabilir. Mikoterapi uygulamalarının kapsamlı bir şekilde anlaşılması, modern tıp ile entegrasyonu açısından büyük önem taşımaktadır. Bu çalışmanın amacı, mikoterapi uygulamalarında kullanılan, Liquidambar orientalis Mill. üzerinde yetişen tıbbi mantar türlerini tanımlamak ve halk hekimliğinde kullanımlarını araştırmaktır. Gereç ve yöntem: Çalışmanın materyalini Muğla ili sınırları içerisinde yetişen Liquidambar orientalis üzerinde belirlenen 6 tıbbi mantar türü oluşturmaktadır. Tespit edilen türlerin tanımlamaları uygun mikolojik teknikler kullanılarak mevcut literatüre (Breitenbach & Kränzlin, 1984; Breitenbach J & Kränzlin F, 1984) göre yapılmıştır göre yapılmıştır. Bulgular: Tanımlanan tıbbi mantar türleri; Ganoderma lucidum (Curtis) P. Karst., Trametes versicolor (L.) Lloyd, Auricularia auricula-judae (Bull.) Quél, Fomes fomentarius (L.) Fr., Schizophyllum commune Fr., Lentinus tigrinus (Bull.) Fr.’dir. Sonuç: Tanımlanan tıbbi mantarlar Asya geleneksel tıbbında önemli türlerdir. Bu tıbbi mantarlar, Asya geleneksel tıbbında eski çağlardan beri kullanılmasına rağmen, Türkiye'de iyi bilinmemektedir. Bu çalışmada, ülkemizde tespit edilen ve özellikle Çin Geleneksel Tıbbında sıklıkla kullanılan 6 tıbbi mantar türü tanımlanmış ve Asya Geleneksel Tıbbında yaygın kullanım alanları ile verilmiştir.
Interest in edible and medicinal macrofungi is millennial in terms of their uses in health and food products in Central Asia, while interest in inedible and medicinal macrofungi has grown in popularity in recent years. Edible and inedible medicinal basidiomycetes were collected during field surveys from different regions of Uzbekistan. The morphological characters and similarity assessment of rDNA-Internal Transcribed Spacer sequence data were used to measure diversity and habitat associations. A number of 17 species of medicinal macrofungi of ethnomycological and medicinal interest was found associated with 23 species of trees and shrubs belonging to 11 families and 14 genera. Polyporaceae and Hymenochaetaceae were represented by the highest number of species followed by Ganodermataceae, Fomitopsidaceae, Auriculariaceae, Cerrenaceae, Grifolaceae, Phanerochaetaceae, Laetiporaceae, Schizophyllaceae, and Stereaceae. The highest number of medicinal basidiomycete species was reported in the following host genera: Acer, Betula, Celtis, Crataegus, Juglans, Juniperus, Lonicera, Malus, Morus, Platanus, Populus, Prunus, Quercus, and Salix. An updated list of edible and inedible medicinal mushrooms identified in Uzbekistan, their morphological characteristics, and phylogenetic placement are given for the first time. Information is provided on their uses in traditional and modern medicine. Their bioactive compounds and extracts can be applied as medicines, as well as food and cosmetic ingredients.
his book, as part of the "Natural Products Chemistry of Global Plants" series, describes in detail the health promoting wild edible and medicinal mushrooms specific to the Himilayas region. The focus of the book is to draw on the rich culture, folklore, and environment of the Upper Himilayas, which represents a scientifically significant region. The Himilayas has rich plant resources and a large diversity of plants and mushrooms, which can provide important health benefits as detailed throughout the text. Drawing attention to these mushrooms with detailed scientific descriptions may help in the awareness and in developing sustainable growth of these important resources.
Features:
Provides an opportunity to describe the wild edible and medicinal mushrooms from this scientifically significant region.
Represents a wider variety of mushrooms than previously published in other books.
Presents more content related to traditional uses, phytochemistry, pharmacology, distribution, processing, toxicology, conservation and future prospective of individual mushrooms.
The plants and mushrooms of the region are valuable resources not only to local populations but to those living outside the region.
Scientists are monitoring the rich Himalayan plant resources and the consequences of climate change on this precarious ecosystem.
Schizophyllum commune Fr. is a wild macro fungus species, which is often used as a food source by the indigenous Kaili tribe along the Palu-Koro fault, Central Sulawesi, Indonesia. This fungus has a wide variety in terms of the weathered wood substrate as a place to grow and is found in almost all types of ecosystems. Although its diversity has been investigated, there is no identification of the weathered wood type as a substrate for growth. Some communities in Indonesia have not also known its potential and benefits. Therefore, this research aims to determine the wood type that grows S. commune fungus, ethnomycology, mineral composition, proximate, and phytochemical compounds. It was carried out using the descriptive explanatory approach and the fungi location as well as wood substrate sampling, was determined through the purposive sampling technique in forest areas, agroforestry, and community gardens along the Palu-Koro fault, Central Sulawesi. The samples of unknown wood types were through the collection of tree parts, namely twigs, leaves, flowers, and fruits, which were brought to Herbarium Celebense, Tadulako University for identification. Analysis of mineral content, proximate, and fungal phytochemical compounds was carried out based on the method according to the existing protocol. The results showed that 92 types of rotted wood found where the fungus S. commune grew, belonged to 36 families. The nutritional content is also good, although it varies based on the type of wood growing media. Therefore, it can be used and processed into various health-beneficial food products. This showed that domestication of the fungus needs to be carried out to support its commercialization as food and medicine in the future.
Mushrooms are among the few natural products that have been relied upon for prophylactic and therapeutic applications in human diseases. They have been referred to as forest gems since they can be picked in the wild or better domesticated for appropriate use. Several scientific studies have been conducted to establish claimed potentials or further probe new areas into which mushrooms can find application. Many disciplines, including mycology, microbiology, physiology, chemistry, genetics, and medicine, among others, conduct research on mushrooms. These enable broad and in-depth studies of mushrooms, to include in vitro and in vivo demonstrations of their bioactivity, structural characterization, and isolation of bioactive components. This chapter highlights the bioactive composition of mushrooms by relating structure to bioactivity and demonstrating therapeutic effects on some human diseases using existing literature. The potentials of mushrooms or their products for the treatment or management of diseases, such as tropical illnesses and COVID-19 pandemic, among other issues, have been discussed. Chemistry of bioactive compounds, structure–activity relationships, patents, and analyses of data obtained have been reported and studied for interpretation of results.
Coffee agroecosystems are a farmer-designed environment, which designed by the producers, and they are postulated as a biodiversity reservoir of the original forest, as many species that once used to live in the forest remain in the coffee plantation, including wild mushrooms. Fungi are sensitive to the use of agrochemicals that favour coffee cultivation, their diversity and productivity decrease if their habitat is drastically modified.
The presence of fungi is an indicator of good practices. The following is information on seven edible species that were the most common species that inhabit coffee plantations in the central region of Veracruz. Morphological descriptions are provided, photographs and a brief review of their nutraceutical* properties, i.e. nutraceutical* properties*, i.e. they have a beneficial effect on human health. At the end of the book a section of recommendations for increasing the natural production of edible mushrooms on coffee farms. In addition to recipes to prepare them, and a glossary of terms that define some technical terms that help to distinguish the species and their species and their technical studies
Throughout history, mushrooms have occupied an inseparable part of the diet in many countries. Mushrooms are considered a rich source of phytonutrients such as polysaccharides, dietary fibers, and other micronutrients, in addition to various essential amino acids, which are building blocks of vital proteins. In general, mushrooms offer a wide range of health benefits with a large spectrum of pharmacological properties, including antidiabetic, antioxidative, antiviral, antibacterial, osteoprotective, nephroprotective, hepatoprotective, etc. Both wild edible and medicinal mushrooms possess strong therapeutic and biological activities, which are evident from their in vivo and in vitro assays. The multifunctional activities of the mushroom extracts and the targeted potential of each of the compounds in the extracts have a broad range of applications, especially in the healing and repair of various organs and cells in humans. Owing to the presence of the aforementioned properties and rich phytocomposition, mushrooms are being used in the production of nutraceuticals and pharmaceuticals. This review aims to provide a clear insight on the commercially cultivated, wild edible, and medicinal mushrooms with comprehensive information on their phytochemical constituents and properties as part of food and medicine for futuristic exploitation. Future outlook and prospective challenges associated with the cultivation and processing of these medicinal mushrooms as functional foods are also discussed.
Mushrooms have remained an eternal part of traditional cuisines due to their beneficial health potential and have long been recognized as a folk medicine for their broad spectrum of nutraceuticals, as well as therapeutic and prophylactic uses. Nowadays, they have been extensively investigated to explain the chemical nature and mechanisms of action of their biomedicine and nutraceuticals capacity. Mushrooms belong to the astounding dominion of Fungi and are known as a macrofungus. Significant health benefits of mushrooms, including antiviral, antibacterial, anti-parasitic, antifungal, wound healing, anticancer, immunomodulating, antioxidant, radical scavenging, detoxification, hepatoprotective cardiovascular, anti-hypercholesterolemia, and anti-diabetic effects, etc., have been reported around the globe and have attracted significant interests of its further exploration in commercial sectors. They can function as functional foods, help in the treatment and therapeutic interventions of sub-optimal health states, and prevent some consequences of life-threatening diseases. Mushrooms mainly contained low and high molecular weight polysaccharides, fatty acids, lectins, and glucans responsible for their therapeutic action. Due to the large varieties of mushrooms present, it becomes challenging to identify chemical components present in them and their beneficial action. This article highlights such therapeutic activities with their active ingredients for mushrooms.
Nowadays, mushrooms with enhanced medicinal properties are being focused on finding such compounds that could modulate the immune systems of the human body. Mushrooms are extensively known for their antimicrobial, antidiabetic, antiviral, hepatoprotective, antitumor, and immunomodulatory properties owing to the presence of various bioactive components. However, a few of them are characterized and reported so far. Various polysaccharides, including β-glucans, are the principal constituent of the mushroom cell wall and play a significant role in their biological activity. This review aimed to focus on a concise report on the extraction process of the active ingredients from a mushroom with some therapeutic applications. Here, we have briefly described the medicinal properties of some commonly used mushroom extracts or their derivatives. It is interesting to note that mushroom is a potential source of many bioactive products that boost immunity. Thus, the development of functional medicinal food is essential for human welfare.
From ancient times, mushrooms are being used as nutraceuticals, food supplements, and dietary fibers for their high nutritional value. Modern medicinal researches have depicted immune-modulating effects of wild edible mushrooms. Among several metabolites of mushroom origin, polysaccharides are known to have the most potential immune-modulatory functions on both innate and adaptive immune systems. Mushrooms polysaccharides (MPs) are the diverse groups of macromolecules which show considerable variability in their physicochemical properties. These variations in properties are considered as determining factors of the immune-stimulation activities. In this present review, a broad outline of different MPs and their purification, the relationship between physical properties and bioactivity, immune cell receptors, and impact on both innate and adaptive immune systems is enlightened.
Mushrooms are macro‐fungi that bear spores enclosed within a fruiting body. They are a well‐known food for humans and have very important nutritional components. They also have great esthetic, culinary, ecological, and commercial importance. Human survival depends upon food, and humans have consumed mushrooms since prehistoric times because edible mushrooms contain an abundance of vitamin B and other several important minerals; they are also low in calories. Several birds and other animals also consume mushrooms, and thus mushrooms are considered an important component of the terrestrial food chain. However, many mushroom species contain toxins and have caused numerous diseases, and death in rare cases.
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Diabetes mellitus is one of the serious problem now a days. It is a chronic metabolic disease, caused by autoimmune devastation of insulin producing β-cell of the pancreas. More than 190 million people are affected worldwide by this disorder and the numbers of affected people are predictable to rise about 380 million by the year 2030. Though various types of anti-diabetic agents are available, including insulin, but they have many side-effects. Anti-diabetic properties containing medicinal plants and natural sources are increasing demand. Medicinal mushrooms are an imitable source of numerous bioactive compounds with anti-diabetic potential and Antihyperglycemic agents. The bioactive compound like polysaccharide, protein, lipids, fiber and some low molecular weight compounds like alkaloids, terpenoids, lactones, lectines and phenolic substances are involved in many diseases as therapeutic mediator and also have been showed a major milestone for the cure of diabetes. In this review, we have discussed the anti-diabetic properties of mushrooms. We explored the medicinal properties of bioactive compound and metabolites of mushroom in impediment and control of diabetes. The previously published literature shows that mushrooms can be used as safe and effective for diabetes treatment.
(1→3)-β-d-glucans are known as potent inductors of humoral and cell-mediated immunity in humans and animals. (1→3)-β-d-glucans isolated from various sources differ in their chemical structure and physical parameters and consequently in their immunomodulatory potential. In this study the immunomodulatory activity of two (1→3)-β-d-glucans schizophyllan (SPG) and carboxymethylglucan (CMG) was determined and compared on human blood leukocytes in vitro. Both SPG and CMG activated blood phagocytes and lymphocytes as demonstrated by increased whole blood production of reactive oxygen species, by increased production of pro-inflammatory cytokines IL-6, IL-8, and TNF-α, by increased surface expression of CD69 on lymphocytes, and by altered expression of CD11b and CD62L on polymorphonuclear leukocytes and monocytes. SPG demonstrated a significantly higher potential to stimulate blood phagocytes and production of selected pro-inflammatory cytokines than CMG. The higher potency of SPG to stimulate human blood phagocytes in vitro could be caused by factors such as higher branching frequencies or neutral polymer charge of SPG or different conformation in solution if compared with CMG.
β-Glucans were identified 36 years ago as a biologic response modifier that stimulated tumor rejection. In vitro studies have shown that β-glucans bind to a lectin domain within complement receptor type 3 (CR3; known also as Mac-1, CD11b/CD18, or αMβ2-integrin, that functions as an adhesion molecule and a receptor for factor I-cleaved C3b, i.e., iC3b) resulting in the priming of this iC3b receptor for cytotoxicity of iC3b-opsonized target cells. This investigation explored mechanisms of tumor therapy with soluble β-glucan in mice. Normal mouse sera were shown to contain low levels of Abs reactive with syngeneic or allogeneic tumor lines that activated complement, depositing C3 onto tumors. Implanted tumors became coated with IgM, IgG, and C3, and the absent C3 deposition on tumors in SCID mice was reconstituted with IgM or IgG isolated from normal sera. Therapy of mice with glucan- or mannan-rich soluble polysaccharides exhibiting high affinity for CR3 caused a 57–90% reduction in tumor weight. In young mice with lower levels of tumor-reactive Abs, the effectiveness of β-glucan was enhanced by administration of a tumor-specific mAb, and in SCID mice, an absent response to β-glucan was reconstituted with normal IgM or IgG. The requirement for C3 on tumors and CR3 on leukocytes was highlighted by therapy failures in C3- or CR3-deficient mice. Thus, the tumoricidal function of CR3-binding polysaccharides such as β-glucan in vivo is defined by natural and elicited Abs that direct iC3b deposition onto neoplastic cells, making them targets for circulating leukocytes bearing polysaccharide-primed CR3. Therapy fails when tumors lack iC3b, but can be restored by tumor-specific Abs that deposit iC3b onto the tumors.
Since the publication of the first edition, important developments have emerged in modern mushroom biology and world mushroom production and products. The relationship of mushrooms with human welfare and the environment, medicinal properties of mushrooms, and the global marketing value of mushrooms and their products have all garnered great attention, identifying the need for an updated, authoritative reference. Mushrooms: Cultivation, Nutritional Value, Medicinal Effect, and Environmental Impact, Second Edition presents the latest cultivation and biotechnological advances that contribute to the modernization of mushroom farming and the mushroom industry. It describes the individual steps of the complex mushroom cultivation process, along with comprehensive coverage of mushroom breeding, efficient cultivation practices, nutritional value, medicinal utility, and environmental impact. Maintaining the format, organization, and focus of the previous edition, this thoroughly revised edition includes the most recent research findings and many new references. It features new chapters on medicinal mushrooms and the effects of pests and diseases on mushroom cultivation. There are also updated chapters on specific edible mushrooms, and an expanded chapter on technology and mushrooms. Rather than providing an encyclopedic review, this book emphasizes worldwide trends and developments in mushroom biology from an international perspective. It takes an interdisciplinary approach that will appeal to industrial and medical mycologists, mushroom growers, botanists, plant pathologists, and professionals and scientists in related fields. This book illustrates that mushroom cultivation has and will continue to have a positive global impact on long-term food nutrition, health care, environmental conservation and regeneration, and economic and social change.
Antitumor activities and effects on cellular immunity of Schizophyllan (SPG), a highly purified polysaccharide extracted from the culture filtrate of Schizophyllum commune Fries, and Bestatin (NK-421), an inhibitor of aminopeptidase B discovered in the culture broth of Streptomyces olivoreticuli, were investigated. The optimal dose of SPG monotherapy to manifest an antitumor effect on MH-134 hepatomas transplanted into C3H/He mice was 10mg/kg, both intraperitoneally (i.p.) and subcutaneously (S.C.). The optimal timing of SPG monotherapy was observed in the group which was treated from 1 day after tumor transplantation, resulting in the most prolonged mean survival (MS) and the highest survival rate. In combined therapy with SPG and mitomycin C (MMC), the most prolonged MS was observed in the group which was treated with MMC on day 3 after tumor transplantation and combined with SPG from day 5. Moreover, the effectiveness continued when the same combined therapy was conducted after the removal of transplanted tumors. The highest ADCC activity by spleen cells harvested from the mice in the SPG monotherapy group was obtained on day 12 after tumor transplantation. The ADCC activity tended to become lower in the MMC monotherapy group, but in the combined therapy group with optimal timing, the highest ADCC activity mediated by non-adherent cells was observed on day 14 after tumor transplantation. Suppressed NK cell activity in tumor-bearing mice was increased to normal levels by SPG monotherapy. On the other hand, NK 421 monotherapy did not manifest a satisfactory antitumor effect regarding survival rate, although it potentiated ADCC activity over a wide range of doses, particularly 5 and 10mg/kg. The main cellular component exhibiting ADCC activity induced by NK 421 therapy seemed to be non-T-cells. By NK-421 monotherapy, the suppressed NK cell activity in tumor-bearing mice was restored up to the normal level.
The anti-tumor effect of the combination of sizofiran (SPG) and macrophage colony-stimulating factor (M-CSF) was studied in C 57 BL/6 mice intraperitoneally inoculated with the syngeneic tumor, EL-4 lymphoma. The effect was evaluated by examining the survival time (1), Giemsa-stained specimens (2), surface markers of peritoneal exudative cells (3), the cytotoxic effect of these cells on autologous tumor and Yac-1 lymphoma (4), and the cytokines in ascites (5). The results showed (1) significant prolongation of the survival time, (2) reduction in the number of lymphoma cells in Giemsa-stained specimens, (3) increase in the number of anti-tumor effector cells, (4) increased cytotoxic action of peritoneal exudative cells on autologous tumor and the NK (natural killer) activity, and (5) increased concentrations of TNF-α, IL-6 and IL-1 β in the mice given both SPG and M- CSF, as compared with either single administration. These results demonstrated the effectiveness of a combination of SPG and M-CSF in treating EL-4 lymphoma.
The culture product of Suehirotake (Schizophyllum commune Fries) mycelium (SCP) is supposed to stimulate cellular immunity. In fact, Schizophyllan (β-1,6-branched β-1,3-glucan) contained in SCP has anti-tumor activity. In the present study, we investigated the effects of SCP feeding on cytokine production in mice in order to clarify the immunological effects of SCP as a dietary component. The levels of interleukin (IL)-12 and interferon (IFN)-γ produced in the culture supernatant of spleen cells from SCP-fed mice were significantly high compared to those in control group (P < 0.05). Furthermore, the level of IFN-γ was dependent on the dose of SCP. The level of tumor necrosis factor (TNF)-α was not changed by SCP-feeding. These results suggest that SCP could be useful food with immunomodulating activities by promoting Th 1 immune response via oral route.
Effect of schizophyllan (SPG), a simple glucan produced bySchizophyllumcommune, and other immunostimulants on candidastatic activity of murine macrophage cell line J774.1 was examinedin vitro. The J774.1 cells treated with each immunostimulant were seeded in 96-multiwell tissue culture plates and infected with serially (2-fold) dilutedCandida parapsilosiscells. Fungistatic index (FI) was estimated after 24 hours incubation. (1) When J774.1 cells were cultivated in the presence of SPG at the concentrations of 10⁻⁴-10²μg/ml, the candidastatic activity proved to be augmented, showing diphasic pattern. The first peak was observed at one hour cultivation (FI: 2.5-9.0), and the second between 24 and 72 hours (FI: 2.12-7.25) . (2) In the case of LPS, increase of candidastatic activity (FI: 4-8) was recognized after one hour cultivation at the concentrations of 10⁻⁵-10⁻¹μg/ml, and maintained for 24 hours. (3) The activation of macrophage with krestin (FI: 4-32) could be observed at the higher concentrations (10-500μg/ml) . (4) Lentinan showed weak activation (FI: 2-4) at the concentrations of 10⁻¹-10⁻³μg/ml after 24 hours cultivation. (5) Corynebacterium parvum, BCG-CWS and picibanil activated J774.1 cells at the very narrow range of concentrations after 48 hours cultivation. (6) No enhancement of candidastatic activity could be detected in the cases of lipid A, MDP, MDP-Lys (L18), DMG and levamisole.
We have already demonstrated that various activities including NO (nitric oxide) synthesis in vivo were significantly different between triple helical (SPG) and single helical (alkaline-treated SPG, SPG-OH) beta-glucans, and that beta-glucan-mediated NO synthesis was associated with increased gene expression of IFN-gamma. In this study, we analyzed beta-glucan-mediated NO production in vitro with the concomitant use of IFN-gamma. Proteose peptone-elicited peritoneal macrophages (PM) were collected from male C3H/HeJ mice and cultured with beta-glucans in the presence or absence of IFN-gamma for 24 h. It was found that SPG-OH, but not SPG, enhanced NO synthesis in vitro, especially in the presence of IFN-gamma. Concentrations of interleukin-1 alpha, -6 and TNF-alpha in the culture supernatant of SPG-OH were significantly higher than those in that of SPG. Membrane-associated IL-1 alpha was also high with SPG-OH. Cytokine productivity of PMs, as well as NO synthesis, was elevated in the presence of IFN-gamma. These facts intensely suggest that the single helical conformer of beta-glucan (SPG-OH) is dominant in cytokine production and subsequent NO synthesis.
The immunologic characteristics of a glucan, sizofiran (formerly referred to as schizophyllan), were investigated by determining its effect on various parameters of immune responses in normal, T cell-deficient or Ehrlich ascites fluid-treated mice. Peritoneal exudate macrophages were rendered cytotoxicity to tumorigenic targets by i.m. and i.v. administration of sizofiran to normal and littermate nu/+ mice but sizofiran was without effect in athymic nu/nu and neonatal thymectomized mice. These results suggest that the collaboration between T cells and macrophages take part in the antitumor activity of sizofiran. In normal mice, moreover, sizofiran augmented alloreactive cytotoxic T lymphocyte generation and lymphoblastogenesis but suppressed production of antibodies against sheep red blood cells and decreased helper T cell activity. Sizofiran prevented and restored the suppression of immune responses such as alloreactive cytotoxic T lymphocyte induction, lymphoblastogenesis, antibody production and helper T cell development in mice treated with Ehrlich ascites fluid. Thus, it is concluded that sizofiran has a distinct property as a T cell adjuvant and it is also suggested that collaborative T lymphocytes and macrophages play an important role in the mechanism of antitumor action of sizofiran.
Purified schizophyllan (SPG), which was not labeled with radioactive isotopes, was administered intraperitoneally or intramuscularly to female mice of the ICR and DBA strains every third day from the 13th day after sarcoma-180 inoculation to the 28th day. Four days after the last SPG administration, 400 µCi/head of ³H-SPG was injected intravenously. The liver, spleen, bone marrow, lymph nodes, thymus, and tumor were studied with whole-body, microscope, and electron microscope (EM) autoradiography I ARG). Anesthetized animals were used for whole-body ARG after tissue pieces were removed and fixed for micro-ARG and EM-ARG. In whole-body ARG, ³H-SPG was mainly accumulated in the liver, spleen, lymph nodes, thymus, bone marrow, and a capsular belt area of the tumor. In the tumor capsular belt area, a very strong accumulation was observed in ICR mice, but the accumulation was very weak in DBA mice. In micro-ARG, ³H-SPG was incorporated in the reticuloendothelial cells; Kupffer's cells in the liver, and reticulum cells and macrophages in the spleen, bone marrow, lymph nodes, and thymus. A large number of macrophages in the tumor capsular belt area were observed migrating between the tumor cells and ³H-SPG was strongly incorporated in their cytoplasm in ICR mice. But only a few macrophages were observed there in DBA mice. In EM-ARG, ³H-SPG was accumulated in special lysosomal granules in the reticuloendothelial cells, including Kupffer's cells and macrophages. The special granules were enveloped with a limiting membrane, and were composed of a compact fine filamentous substance and an electron opaque lysosomal cap structure (filamentous ball, Fb). The nature of these fine Fbs was exactly the same as that of SPG macromolecules observed in the negatively stained samples. There were no great differences on the observations by ARG and histology between the SPG-treated ICR and DBA mice, except in the tumor region. A large number of macrophages with many intracytoplasmic Fbs were migrating into the sarcoma nest in the capsular area, and many sarcoma cells were rapidly degenerating or had disappeared in the SPG-treated ICR mice. In DBA mice, however, there were no significant changes in the cancer nests; the cancer cells were growing and increasing rapidly, and the animals died within a month. These autoradiographic data suggest that the SPG granules (Fbs) containing activated macrophages in the ICR tumor nests play an important role in destroying the growing sarcoma cells, but there was no evidence of active macrophages in the DBA sarcoma nests. The Fbs in the macrophages in ICR mice probably produce a large amount of various lysosomal enzymes and act as activators of the destruction of sarcoma cells, but did not act in DBA mice. The reason for such a big difference between the two mouse strains was not clear, but some immunogenomic factors could be concerned. © 1985, JAPAN SOCIETY OF HISTOCHEMISTRY AND CYTOCHEMISTRY. All rights reserved.
The immunomodulating properties of comb-like branched (1→3)-β-d-glucans scleroglucan, schizophyllan and lentinan depend on branching pattern, molecular weight and higher-order structure. The effect of weight average molecular weight Mw and higher order structure of scleroglucan, on stimulation of human monocytes cultured in vitro to secrete tumor necrosis factor-α (TNF-α) was investigated. The higher order structures of the scleroglucan samples were determined by electron microscopy. The data showed that the samples with a linear wormlike, triple helical structure with Mw less than 50×104 g/mol or larger than 110×104 g/mol stimulated the monocytes more efficiently than samples with Mw in the range (67–110)×104 g/mol. The denaturation of the linear triple helices by NaOH (>0.25 M), followed by neutralization yielded blends of linear and macrocyclic topologies with concomitant irreversible reduction of the cytokine inducing activity compared with the untreated scleroglucans. The dose-dependent ability to activate monocytes to cytokine production was not restored following annealing of the denatured–renatured samples, despite the fact that electron micrographs revealed similar structures of these annealed samples to the starting material. Pre-incubation of monocytes with antibodies against cluster of differentiation antigens CD14 or CD11b reduced the scleroglucan potency to stimulate TNF-α secretion mainly for mAb against CD14 in the presence of serum.
We investigated the effect of a fungal component, soluble �- glucan, on secretory functions of murme alveolar macrophages (AMs) in vitro. Stimulation by �-glucan (500 jigJmL) or interferon-y (IFN-'y; 100 U/mL) alone had a slight effect on AM functions, but when AMs were incubated together with �-glucan and IFN-y, the production and secre- tion of some immune mediators, such as nitric oxide, interleukin- 1 (IL- 1 ), IL-6, and tumor necrosis fac- tor-a (TNF-a), were markedly augmented. This combined effect of �-glucan and IFN-y was based on a priming effect of IFN-y, because prestimulation with IFN-y followed by (�-glucan induced high nitric oxide production of AMs, but reversal of the se- quence of treatments had only a slight effect. We also found that premcubation of AMs with IFN-? en- hanced the binding of fluorescein-labeled �-glucan on the AM surface, and this increased binding was abrogated to the control level by the addition of three species of soluble unlabeled (1 -+3)-�3-D-glucans but not by soluble a-glucan. These data imply that the priming effect of IFN-y on the AM response to �-glucan was dependent, at least in part, on the enhancement off�-glucan specific binding sites on the AM surface. It was suggested that IFN-'y is one of the principal factors controlling the pulmonary immune system against both severe fungal infection and in- flammation via AM activation at the alveoli. J. Leukoc. Biol. 60: 118-124; 1996.
A native sample of a Schizophyllum commune polysaccharide (schizophyllan) and its sonicated fragments, ranging in weight-average molecular weight (M w) from 10 5 to 6 × 10 6 g mol -1, were studied by ultracentrifugation and viscometry in water at 25°C, in which schizophyllan has been found to exist as a triple helix. Measurements of intrinsic viscosity [η] and limiting sedimentation coefficient s 0 showed that the schizophyllan triple helix is almost perfectly rigid up to M w = 5 × 10 5 g mol -1 but acquires flexibility for higher M w. The data in the lower molecular weight range were analyzed by Yamakawa's theory for [η] and Yamakawa-Fujii's theory for s 0 of a long rigid cylinder, with the result that M L (the molar mass per unit cylinder length) = 2150 ± 150 nm -1 and d (the diameter) = 2.6 ± 0.4 nm. This M L gives the pitch of the triple helix per β-1,3-D-glucose residue a value of 0.30 ± 0.02 nm, which agrees closely with the reported pitches for lentinan and a β-1,3-D-xylan in the crystalline region. The d value 2.6 nm is consistent with the diameter of the model triple helix for schizophyllan. With M L = 2150 ± 150 nm -1 and d = 2.6 ± 0.4 nm, the persistence length that allows the theoretical curves of s 0 and [η] for wormlike cylinders to fit the present data was found to be 200 ± 30 nm. This value indicates that the schizophyllan triple helix is stiffer than that of native collagen, a known triple-helical biopolymer.
The filamentous fungus Schizophyllum commune secretes three major biopolymers into liquid growth media. These include a 24 kiloDalton hydrophobin, a 17 kiloDalton protein, and a high molecular mass polysaccharide, schizophyllan. The fungal culture supernatant forms sodium dodecyl sulfate resistant coatings on both hydrophobic and hydrophilic surfaces as demonstrated by water contact angle measurements and atomic force microscopy. Specific digestion of the schizophyllan from the supernatant has little effect on coating integrity on a hydrophobic surface. By contrast, enzymatic digestion of the hydrophobin eliminates the ability of the remaining supernatant components to assemble as a stable entity on a hydrophobic surface. Digestion of either the polysaccharide or the hydrophobin prevents stable association with a hydrophilic surface. Previous studies have demonstrated the role of hydrophobin in forming stable coatings on various surfaces; however, the synergistic interaction of schizophyllan with hydrophobin was not considered. Our data form the basis for a preliminary model in which hydrophobin is stabilized in the culture supernatant by a protective hydrophilic corona. Coalescence of hydrophobin onto solid mica or Parafilm® surfaces is favored over self-association in the presence of schizophyllan. © 1999 John Wiley & Sons, Inc. Biopoly 49: 621–633, 1999
From sedimentation equilibrium, light scattering, and viscosity measurements on a series of native and sonicated samples of schizophyllan, and extracellular β-1,3-D-glucan, the following results were obtained: (i) weight-average and z-average molecular weights (M̄w and M̄z) in water are about three times as large as those in dimethylsulfoxide (DMSO); (ii) the exponent in the Houwink-Mark-Sakurada intrinsic viscosity relation in water is close to 1.7, whereas in DMSO it is 0.68; (iii) intrinsic viscosities of samples with M̄w below 5 × 105 in water at 25°C can be fitted by Yamakawa's theory for along rigid rod if the pitch (1.836 nm) of the triple helix of Atkins et al. and the diameter (3 nm) estimated from the model triple helix are used; (iv) intrinsic viscosities in water-DMSO mixtures at 25°C undergo and almost discontinuous decrease when the weight fraction of DMSO in the mixture increases to about 87%. These results combined lead to the conclusion that schizophyllan dissolves in water as a triple helix similar to that proposed by Atkins et al. and that the triple helix in aqueous DMSO solution “melts” abruptly to single chains when the DMSO coposition reaches about 87 wt%. It was also found that the triple helix is not recoverable once it is broken in DMSO.
Gels of the glucan schizophyllan, consisting of a 1,3-β-d-linked backbone of glucose residues with 1,6-β-d-glucosyl side groups, were found to show melting behaviour in the temperature range between 5 and 20°C, depending on the glucose concentration in the solvent (0–50 wt% glucose). While the qualitative features of the modulus-versus-concentration and modulus-versus-temperature rheological data for the gels can be modelled using modified cascade theory (which implicitly assumes that no sub-level of organisation exists in the gel structure), a consistent quantitative fit cannot be achieved. The inconsistencies found are consistent with the idea that the gel is composed of bundles (consisting of many triple helices of schizophyllan) with strong intra-bundle attraction and weak inter-bundle forces. Transmission Electron Microscopy (TEM) micrographs of diluted samples indicate that schizophyllan polymers engage in lateral aggregation of triple helical strands at temperatures below the melting temperature, suggesting that indeed bundles of polymers will be present in the gel state.
During our stay of several years in the south of the Upper-Shaba region of Zaïre, we observed that the consumption of wild
mushrooms constitutes an appreciable food supplement for the local populations. It seemed of interest to us to try to determine
the species consumed as well as their food value—this type of systematic study having not yet been undertaken in Central Africa.
Our preliminary data have already been published in 1973 (Thoen et al.).
Two species of mushrooms Schizophyllum commune and Lentinus edodes from Northeast India were assessed for their nutritive value. Protein contents of S. commune (16%) and L. edodes (23%) were high, but fat content was low (2%) in both the mushrooms. Oleic and linoleic acids accounted for 72–77% of the total fat in both the mushrooms. Essential amino acid contents of S. commune and L. edodes were 34% and 39%, respectively. The chemical scores of S. commune (28) and L. edodes (29) were low compared to whole egg protein. Methionine was the limiting amino acid in both the mushrooms. Protein quality evaluation by NPR (net protein ratio), NPU (net protein utilization) and TDP (true digestibility of protein), showed that the mushrooms were comparatively much lower then casein in all the parameters examined. Animals on L. edodes showed significantly (p < 0.05) higher NPR, RNPR, and NPU than animals on the S. commune diet. True protein digestibility of the L. edodes diet was also significantly (p < 0.05) higher than the S. commune diet.
Effects of schizophyllan (SPG) and several antibiotics in combination against experimental Pseudomonas aeruginosa infection were examined.
(1) Whereas the increase in protective effect of SPG was not observed in combination with carbenicillin or sulbenicillin, remarkable effects could be recognized in combination with dibekacin or gentamicin (GM). The combined therapy with SPG and GM proved to be most excellent.
(2) The time course for changes of viable number of Ps. aeruginosa in various organs of mice revealed that the multiplication of the infected bacteria was more markedly inhibited in mice treated with SPG and GM in combination than those treated with each alone.
(3) The increase in bactericidal activity of the peritoneal exudate cells was more remarkablydemonstrated in the combined treatment with SPG and GM than with each alone, showing the rapid clearance of bacteria from the peritoneal cavity in the former.
(4) The microscopic estimation demonstrated that the increase in both phagocytic index and intracellular digestion of bacteria by cultivated macrophages was larger in combination of SPG and GM than each alone.
(5) The measurement of viable number of bacteria in cultivated macrophages by the platecount method also showed that the ingestion and bactericidal activity within the cells were much higher in combined treatment with SPG and GM than each alone.
The macrophage expresses a variety of cell surface lectins with activities that support specific functional roles and correspond to various differentiation states characteristic of this cell type. Recently, research has been carried out to investigate the mannose receptor, the advanced glycosylation end products receptor, the mannose-6-phosphate-receptor, the beta-glucan receptor, sialoadhesin and several galactose-specific binding proteins.
Several hundred natural polysaccharides are currently known and provide one of the richest and oldest reservoirs of structurally and functionally diverse biopolymers. Water soluble polysaccharide hydrocolloids are abundant in nature, present in many plant sources but only a restricted number is of therapeutical interest. For medical purpose many uses were proposed and have been established ever since, and new areas of pharmaceutical/medical uses are constantly being discussed (1).
Activation of the alternative (APC) and classical (CPC) pathways of complement by fungal (1----3)-beta-D-glucans having different degrees of branching (DB) and different conformations were examined by using human serum and plasma. The glucans used in this study were curdlan (no branch; 0/1), grifolan (one branch in every third main chain unit; 1/3), schizophyllan (1/3), SSG (1/2), and OL-2(2/3). Triple or single helix conformer of these glucans were prepared by heating at 150 degrees C or dissolution in sodium hydroxide. Activation of APC by these glucans were dependent on incubation time, concentration, molecular weight, and DB. Interestingly, the triple helix conformer of all glucans tested activated APC stronger than a single helix one. The activity of branched glucans in plasma was weaker than those in serum. On the other hand, in the case of CPC, a single helix conformer activated CPC stronger than a triple helix one, and the activity was dependent on DB. Activation of CPC by a single helix conformer was thought to be dependent on the binding of beta-glucan to immunoglobulin in serum, because the complex was clearly detected by gel permeation chromatography only in the case of single helix one. From these results, it appears that the different conformers were recognized by the host complement systems in different ways. (1----3)-beta-D-Glucan is one of the major constituents of fungal cell wall and is thought to be clearly recognized by the host immune systems.(ABSTRACT TRUNCATED AT 250 WORDS)
We present additional evidence that plasma from patients with deep-seated mycoses contains (1-->3)-beta-D-glucan. Digestion of such samples with endo-(1-->3)-beta-D-glucanase completely abolished the ability of the plasma to activate factor-G, a horseshoe crab coagulation enzyme that is extremely sensitive to this polysaccharide. Measurement of plasma (1-->3)-beta-D-glucan is a promising method for the diagnosis of deep-seated mycoses and for monitoring the response of these infections to antifungal therapy.
The efficacy of Sizofiran(SPG), a highly purified beta-1,3-D-glucan from the culture broth of basidiomycetes Schizophyllum commune Fries, in combination with local irradiation was investigated using squamous-cell carcinoma NR-S1 and syngeneic hosts of C3H/He mice. NR-S1 tumor was implanted sc in the thigh of C3H/He mice. When tumor grew to 4 mm in diameter, the local irradiation of 55 Gy was delivered. SPG was injected im at a dose of 5 mg/kg. When SPG was administered after irradiation, remarkable inhibition of tumor growth was observed in comparison with the radiation alone group. Furthermore, the combination effect of radiation and active immunotherapy using mitomycin C-treated NR-S1 cells as vaccine was examined. When radiotherapy and active immunotherapy were combined with SPG, suppression of tumor growth was observed from an early stage in comparison with the group which was not administered SPG. SPG also inhibited the pulmonary metastasis of NR-S1 tumor after radiotherapy.
The effect of SPG on leukocytes has been studied in 20 patients with oral carcinoma and the actions have been analysed in vitro. SPG 1 mg/kg was administered intramuscularly twice weekly. Peripheral venous blood was collected before, and 1 week and 2 weeks after the initiation of SPG treatment. Both CD16+CD57- and CD16-CD57+ cell populations were significantly increased after treatment, but no T cell subset varied. While enhancement of lymphokine-activated killer activity could not be found, an increase in natural killer (NK) activity was observed in 15 of the subjects, and the mean NK level was significantly increased from an initial 34.7 +/- 18.7% to 46.4 +/- 16.5% after two weeks of injections. O2-production by polymorphonuclear leukocytes (PMNL) was stimulated 6 h after SPG injection. When PMNL were treated in vitro with SPG 32 micrograms/ml, enhanced O2-generation was induced and protein kinase C (PKC) activity in a membrane fraction increased. SPG did not directly affect non-specific PMNL killing of K562 cells or antibody-dependent cell mediated cytotoxicity against Raji cells, but non-specific PMNL killing was enhanced by culture-conditioned medium from peripheral blood mononuclear cells (PBMC) containing 10 micrograms/ml SPG. Interleukin-1 beta, -3, -4, -6, tumour necrosis factor-alpha, granulocyte-macrophage colony stimulating factor and IFN-gamma levels in the conditioned medium were not increased compared with medium from PBMC not treated with SPG. No clear increase of these cytokines was found in serum from the SPG-treated patients. From the above results, enhancement of PMNL O2-generation by SPG seems to be a direct action of SPG, but the mechanism of elevation of the non-specific killing activity of PMNL and NK cells is not known. Perhaps other cytokines than those assayed have participated in increasing non-specific cytotoxicity.
Augmentation of anti-tumor effect of interleukin 2 (IL-2) with sizofiran (SPG) was demonstrated with in vivo and in vitro experiments. C3H/He mice with subcutaneously inoculated X5563 tumor were used as experimental models. IL-2 at a dose of 2 X 10(4) units per mouse by subcutaneous injection, and/or SPG at a dose of 0.1 g per mouse by intramuscular injection were given every other day for a total of ten times. Tumor infiltrating lymphocytes (TIL) were investigated with the avidin-biotin peroxidase complex method. Cytotoxic activity of mice spleen cells after the therapies against YAC-1, X5563 and MH134 were tested with 51Cr release assay. IL-2 or SPG alone suppressed tumor growth in vivo, although not significantly. Combination therapy with IL-2 and SPG suppressed tumor growth in vivo significantly (p = 0.04). Mice treated with the combination survived longer than the mice treated with the single drug (p less than 0.05) and the controls (p less than 0.001). Immunohistologically, more TILs were seen in the combination group than the other groups. In the cytotoxicity study, 3 days after initiation of the therapies, augmentation of natural killer (NK) activity was greater by the combination than by IL-2 or SPG alone. After incubation with IL-2, the spleen cells from mice treated with the combination showed higher cytotoxicity against X5563 or MH134 tumors than those treated with the single drug or controls. Obtained results suggested that combination therapy with IL-2 and SPG effectively induced NK cells and lymphokine-activated killer cells in vivo and may lead to greater clinical benefit in the treatment of malignancies.
To examine whether sizofiran (SPG), a polysaccharide isolated from Schizophyllum commune Fries, could modulate the immune response of immunocompetent cells to hepatitis B virus (HBV) nucleocapsid antigens, we investigated in vitro the production of interferon-gamma (IFN-gamma) and antibody (antibody to HB core and e antigens; anti-HBc and anti-HBe), and proliferation by peripheral blood mononuclear cells (PBMC) from six patients with chronic hepatitis B and four control individuals in the presence of recombinant HBcAg and purified HBeAg. Sizofiran alone in culture and in combination with HBV Ag was found to enhance IFN-gamma production and the proliferative response of PBMC from the patients compared with corresponding medium or HBV Ag alone culture. In contrast, antibody production was not elicited by SPG alone, but amplified by the drug in HBcAg-stimulated culture. In vitro leukocyte IFN-alpha addition increased IFN-gamma production, but suppressed the proliferation of PBMC from both controls and patients in the presence or absence of SPG and HBV Ag. These results indicate that SPG is able to modulate both cellular and humoral immune responses specific for nucleocapsid antigens in patients with chronic hepatitis B.
The number of bone marrow cells in C3H/He mice was reduced 3-4 days after treatment with 130 mg/kg intraperitoneal 5-fluorouracil (5-FU). Higher rates of spontaneous proliferation and natural killer (NK) activity, accompanied by an increase in asialoGM1-positive cells, were observed in treated mice. When sizofiran at a dose of 200 micrograms/animal was intramuscularly injected after 5-FU treatment, the rates of proliferation and NK activity of bone marrow cells were higher than with 5-FU alone. The cell number was not influenced by sizofiran alone. These results indicate that all precursors of the various mature cell types (including NK cells) differentiate and regenerate rapidly to replace cells damaged by 5-FU treatment, and that sizofiran has the potential to assist this recovery. These results suggest that administration of sizofiran after chemotherapy may be useful in cancer patients.
Twenty mg of sizofiran (Schizophyllum glucan: SPG) was i.m. administered one day prior to surgery, or the same dose was injected 8 days and one day before surgery to 40 patients with cervical cancer and 15 with a benign tumor. Frozen sections of fresh pelvic lymph nodes from these patients obtained during surgery were stained by the ABC (Avidin-biotin-peroxidase complex) method with several monoclonal antibodies to define the surface phenotype of mononuclear cells. SPG led to a great increase in the number of cells stained with interleukin-2 receptor (IL-2R) and Leu 3a antibodies, mainly in PC, but with only a slight increase in the number of cells stained with Leu 2a, 7, 11, and M3 antibodies. This augmenting effect was more prominent in patients receiving two SPG injects that in those with a benign tumor. These results suggest that stimulus with some antigen (cancer antigen in the present study) may be required to induce immuno-augmentation by SPG which has no antigenicity. Interestingly, the above augmenting effects could be seen even in metastatic lymph nodes from advanced cervical cancer patients. SPG was thus revealed to be a potent biological response modifier leading to augmented helper T (Th) cell functions of pelvic lymph nodes in cervical cancer patients, among which an enhanced IL-2/IL-2R system was noted.
Degradation and excretion of Sizofiran (SPG), an anti-tumor polysaccharide, were studied in rats after a single or multiple administration. After a single intravenous injection of [14C]SPG (3 mg/kg), SPG distributed in the liver was degraded at very slow rate to SPG-like substances (SPGLS) having lower molecular weight than that of SPG, while SPG in the spleen and mesenteric lymph node was metabolized at much slower rate than that in the liver. In the experiment with multiple subcutaneous administration, SPG was also found to be present mainly as SPGLS in the liver, but almost as an unchanged SPG in the spleen. SPG was excreted in the urine mainly as metabolites with a molecular weight of less than 10000. These results indicate that degradation of SPG to lower molecular weight-SPGLS is a prerequisite for efficient urinary excretion and the degradation occurs mainly in the liver.
Sixty-two patients with gynecological disease, who were treated with sizofiran (SPG) intramuscularly before laparotomy or with recombinant interferon gamma (IFN) intraperitoneally on the day of the laparotomy, were studied to investigate the change on the number and function of peritoneal macrophages (PM) obtained by peritoneal washing on the day and on the 1st and 4th days after the laparotomy. SPG significantly increased the number of PM by the 1st day, and IFN by the 4th day (p less than 0.05). However, IL-1 and IFN-gamma secretion by PM were not activated by SPG or IFN treatment, respectively. When patients were treated with these two agents simultaneously, the number of PM was significantly increased by both the 1st and the 4th day (p less than 0.05), and IL-1 and IFN-gamma secretion by PM were also significantly activated by the 1st day (p less than 0.05). These data suggest that SPG and IFN had a synergistic effect on increasing the number of PM and on activating the secretion of cytokines by PM, and that the priming with SPG played an important role in the activation of PM function by IFN.
The effect of a single or multiple administration of sizofiran (SPG), an anti-tumor polysaccharide, on a hepatic drug-metabolizing enzyme system was studied in rats. When SPG was given intravenously at a single dose of 0.5 or 10 mg/kg, no alteration was observed in activities of aminopyrine (AP) N-demethylase and aniline hydroxylase, and in cytochrome P-450 (P-450) content in the livers of rats 48 h after dosing. However, only AP demethylase activity decreased by 34% after the administration of 200 mg/kg. Similarly, no change in the hepatic enzyme activities and P-450 content was observed for up to 180 d after a single dose of 10 mg/kg. Subcutaneous treatment of animals with either 10 or 40 mg/kg dose for 3 and 6 months resulted in no alteration in the enzyme activities and P-450 content. These results may indicate that the therapeutically effective dose of SPG has no effect on a hepatic drug-metabolizing enzyme system in rats.
SPG1 and SPG2 are polysaccharides extracted respectively from fermented cultural mycelium and fermentation fluid of Schizophyllum commune. This paper reports the effect of SPG1 and SPG2 on concanavalin A (Con A) induced proliferation of lymphocyte from C57BL/6J mice in vitro. SPG1 (10, 25, 50 and 100 micrograms/ml) and SPG2 (10, 50 and 100 micrograms/ml) was found to significantly increase lymphocyte proliferation. In addition, SPG1 (10, 25, 50 and 75 micrograms/ml) antagonized the suppressive effect of hydrocortisone on proliferation of mouse spleen cells, while SPG2 did not. In vivo, at the dose of 2.5 and 5.0 mg/kg ip for 9 days, SPG1 and SPG2 remarkably enhanced the delayed-type hypersensitivity to 2, 4-dinitrochlorobenzene (DNCB) in mice. SPG1 (1.25, 2.5 and 5.0 mg/kg, ip for 1 day) and SPG2 (2.5 and 5.0 mg/kg, ip for 1 day) promoted the plaque forming cell (PFC) response to sheep red blood cells (SRBC) in mice. The effects of SPG1 and SPG2 on immune function were studied in aged immunodeficient mice. SPG1 (10 and 25 micrograms/ml) and SPG2 (25 micrograms/ml) was found to enhance the Con A induced lymphocyte proliferation in 14 months aged mice. At the dose of 2.5 mg/kg, SPG1 and SPG2 produced respectively 162.1 and 136.0% increase in PFC response in 14 months aged mice.
Correlation between the higher structure and biological functions of lentinan, a beta-1,6;1,3-glucan capable of potentiating T- and non-T-cell-mediated responses, were investigated by measurements of optical rotation and some biological responses. The addition of urea or dimethyl sulfoxide decreased specific rotation at 589 nm, [alpha]D, of lentinan in a concentration-dependent manner and the removal of these denaturants resulted in the recovery of [alpha]D values. Measurements of optical rotatory dispersion in the spectral region between 600 and 200 nm showed the change in the higher structure of lentinan more clearly. Denaturation and renaturation of lentinan using urea and dimethyl sulfoxide were associated with the decrease and the recovery of antitumor activity against P-815 mastocytoma and vascular dilation and hemorrhage-inducing activity, found to be T-cell-mediated responses. Lentinan was also denatured by NaOH and the transition of [alpha]D values and optical rotatory dispersion curves were seen in the manner of two concentration-dependent phases. Removal of NaOH led to the recovery of optical rotation of lentinan and its antitumor and vascular dilation and hemorrhage-inducing activity. However, recovery of these bioactivities was more difficult in the case of the higher concentrations of NaOH above 2% than the lower ones. During the process of renaturation of lentinan, random aggregation may take place. An increase of serum acute phase proteins, a non-T-cell-mediated response caused by lentinan, was not affected by the change of the higher structure of lentinan.
Mixed-function oxidase activities of hepatic microsomal preparations from rats were examined after intraperitoneal administration of sizofilan (SPG), an immunomodulator. Repeated doses of SPG (3 mg/kg/12 hr, 4 times) depressed the hepatic cytochrome P-450 content and the activities of aminopyrine N-demethylase and aniline hydroxylase.
Excretion and distribution of sizofiran (SPG), an antitumor polysaccharide, were investigated after a single intravenous (i.v.) injection of ¹⁴C-labelled SPG(¹⁴C-SPG) to rats. Radioactivity was very slowly eliminated from the body. It was mainly excreted in the urine. When ¹⁴C-SPG was given at doses of 0.2mg and 2 mg/kg, the radioactivity recovered in the urine within 6 months was 41% and 26%, respectively. Radioactivity much less than urinary excretion was also observed in the feces and expired gas. In whole-body autoradiographic study, radioactivity was distributed selectively in the reticuloendotherial tissues such as liver, spleen, mesenteric lymph node and bone marrow at 24 h after dosing, and still remained to be considerably high in the spleen, lymph node, liver and thymus at six months after dosing. SPG-like substances, isolated from the livers, spleens and mesenteric lymph nodes of rats given non-radioactive SPG, seemed to have a similar chemical structure to that of SPG and were shown to have a similar potent antitumor activity to that of SPG against sarcoma-180 murine tumor.
Antitumor effect against syngeneic or allogeneic tumor and biological response modifying activities of schizophyllan (SPG, a β-1,3-D-glucan with a β-1,6 linked D-glucose residue isolated from Schizophyllum commune Fries) were investigated. SPG exhibited the significant antitumor effects against syngeneic murine tumors, adenocarcinoma 755 (C57BL/6 mice) and MM 46 mammary carinoma (C3H/He mice) as well as sarcoma 180. Antitumor effect of SPG significantly diminished in mice neonatally thymectomized and treated with antithymus globulin. SPG markedly augmented the developments of allogeneic cytotoxic lymphocytes in vivo, or in vitro. Thus, antitumor effect of SPG was considered to be due to the augmentation of host defense mechanism closely connected with the T-cell functions. SPG enhanced the carbon clearance rate, accumulated into the reticuloendothelial system (RES) and increased the serum lysozyme activity, showing the stimulation of RES. Moreover, the macrophages activated with SPG exhibited the increases of cellular enzyme activities and spreading in addition to the development of cytolytic activity against tumor cells. These results taken together with the loss of antitumor effect of SPG in mice treated with trypan blue show that the mode of antitumor effect is expressed by cytotoxic macrophages in addition to T-lymphocytes. The enhancing effects of SPG on natural killer cell activity and serological factors possibly related to its antitumor activity were also observed. In conclusion, the present results of the pharmacological and toxicological studies suggest that SPG is a safe and useful immunoadjuvant of cancer therapy.
Anti-tumor activity was studied in mice injected with Schizophyllan (SPG), a glucan produced by Schizophyllum commune Fries. SPG-injected mice rejected subcutaneously inoculated sarcoma-180 and the anti-tumor activity was shown to be mediated by host spleen and lymph node cells. The anti-tumor activity lasted as long as 60 days after the SPG administration as assessed by transfer of cells into normal recipients. Cells involved in anti-tumor activity were shown to be T lymphocytes since anti-tumor activity was diminished when lymph node cells from SPG-treated mice were treated with anti-Thy-1.2 sera plus complement, whereas cells passed through a nylon wool column retained the activity. Macrophages were also shown to be involved since administration of carrageenan or trypan blue into the host decreased the inhibition ratio of tumor growth. It was concluded that anti-tumor activity in SPG-treated mice was mediated by the cooperation of T lymphocytes and macrophages, thus the impairment of either function decreased anti-tumor activity.
The effect of a glucan, Schizophyllan (SPG), on pulmonary metastases in syngeneic mice bearing Lewis lung carcinoma (3LL) was examined. As a model of pulmonary metastases, 3LL cells were implanted into the footpads of C57BL/6 mice, the resulting primary tumor was removed 9-10 days later. The inhibitory effect of SPG was evaluated from the number of pulmonary surface nodules on the lungs about 3 weeks after tumor implantation. SPG was found to have antimetastatic activity, which depended on its dose and time of injection. A single injection of 100 or 200 mg/kg or daily injections of 20 or 50 mg/kg of SPG after removal of the primary tumor markedly inhibited pulmonary metastases. Combined therapy with cyclophosphamide and SPG significantly prolonged the survival of mice with pulmonary metastases. Enhancement of the in vitro cytotoxic activity of peritoneal macrophages and bronchoalveolar or whole lung cells against 3LL cells was noted in SPG-treated mice on day 7 after a single intraperitoneal injection of 100 mg/kg SPG. Intravenous transfer of peritoneal macrophages activated with SPG inhibited the development of pulmonary micrometastases.
The antitumor activity of schizophyllan (SPG) against syngeneic ACI/N rat tumor, AMC-60 fibrosarcoma and BC-47 bladder cancer was investigated. Intramuscular injection of SPG caused a marked suppression of AMC-60 tumor growth. Results obtained with cytotoxicity tests in vitro and lymphoblastogeneic response in vitro suggest the association of enhanced macrophage cytostasis and high reactivity of lymphoid cells with the resistance of the host to AMC-60 tumor. Moreover, SPG showed pronounced antitumor activity against BC-47 bladder cancer. The highest therapeutic effectiveness was obtained when SPG injection was started at an advanced stage of the tumor, 4 out of 15 rats treated being completely cured of cancer. Cytotoxicity tests in vitro and neutralization tests in vivo indicated the important role of cytotoxic lymphocytes as well as activated macrophages in the host defence mechanism against BC-47 cancer. This, taken together with the fact that the rats cured completely by SPG therapy acquired transplantation resistance to BC-47 cancer, shows that SPG may promote tumor immunity in the host.
We tested anti-tumor activities of macrophages treated with a neutral polysaccharide, schizophyllan (SPG), against syngeneic and allogeneic tumor cell lines. SPG was a macrophage stimulant which was not mitogenic to lymphocytes. That made a sharp contrast with the data that Corynebacterium parvum, BCG, and muramyl dipeptide (MDF) were macrophage stimulants which had lymphocyte-activating properties. Treatment of SPG-treated PEC with Thy12 monoclonal antibody and guinea pig complement did not affect the capabilities of tumor-cell-growth suppression by the treated PEC. Thus, the effector cells were peritoneal adherent cells (macrophages morphologically) and effector-to-target contact seemed to be necessary for effective tumor-cell-growth inhibition, although contradictory data exist for this. Murine peritoneal adherent cells harvested 4 days after a single IP injection of SPG at a dose of 100 mg/kg body weight of mouse showed the most prominent cytostatic and cytotoxic activities against syngeneic and allogeneic tumor cells. The distribution of anti-tumor activity in macrophages of various sizes followed the same pattern as macrophages treated with C. Parvum, i.e., larger macrophages showed more remarkable anti-tumor activity. Crude nonadherent peritoneal cells incubated with SPG at a concentration of 10 micrograms/ml, 100 micrograms/ml, or 1 mg/ml did not secrete lymphokine that rendered macrophages cytotoxic, while ConA-treated nonadherent cells did so. Furthermore, spleen cells treated with SPG in vivo did not secrete macrophage-activating lymphokine in the presence of SPG. On the other hand, addition of 1 mg/ml of SPG-treated peritoneal adherent cells and bone-marrow-derived macrophages in vitro rendered them cytotoxic to a moderate degree. This implies that SPG may activate macrophages directly, allowing them to become cytotoxic in the peritoneal cavity. Lastly, SPG could induce production of II-1-like factor to a moderate degree. SPG, whose molecular structure is well elucidated, will provide us with a strong tool to analyze the mechanism of macrophage activation both in vitro and in vivo.
Schizophyllan, a water-soluble beta-D-glucan elaborated by Schizophyllum commune Fries, was partially depolymerized by ultrasonic irradiation to a low-molecular-weight polysaccharide, designated "sonic-degraded schizophyllan". Both native and degraded polysaccharides exhibited essentially the same antitumor activities against Sarcoma-180 ascites. Both glucans are comprised solely of D-glucose residues and have a main chain of (1 leads to 3)-beta-D-glucopyranosyl residues, one out of three glucose residues being attached as single, (1 leads to 6)-beta-D-glucopyranosyl groups. Although both glucans have similar structural features, significant differences are observed in such physical properties as molecular weight and intrinsic viscosity. End-group analysis by using radioisotope-labeled glucans suggests that ultrasonic degradation occurs mainly by cleavage of glycosidic bonds of the main chain of schizophyllan. The molecular weights of the native and sonic-degraded schizophyllan were shown to be 75% of those of corresponding, original schizophyllan preparations, suggesting that there is no anomalous linkage sensitive to periodate oxidation, and ultrasonic irradiation may cause random hydrolysis of (1 leads to 3)-beta-D-glucosidic linkages in the main chain.
When treated with fungal polysaccharide schizophyllan, mice survived otherwise lethal Sendai virus infection. Both intraperitoneal and oral administrations were effective when sonicated schizophyllan with a relative molecular mass (M(r)) of 4.6 x 10(5) was used. Antiviral antibody in the serum could be detected at an earlier time after virus infection and virus spread in the lung was more efficiently inhibited in schizophyllan-treated mice than in untreated controls. Schizophyllan also augmented protective immune responses induced by low doses of a live Sendai virus vaccine that were insufficient to confer complete protection against challenge infection with a virulent strain. On the other hand, schizophyllan did not influence interferon production in mice whether or not infected with Sendai virus. The present results suggest that schizophyllan confers better protection against virus infection through augmentation of antiviral immune responses and can be used as an immune enhancer.
(1-->3)-beta-D-Glucans exhibit a variety of biological and immunopharmacological activities, and the degree of these activities depends on the nature of the individual glucans e.q. molecular weight, degree of branching and conformation. Based on the generally accepted evidence that the conformation of Sonifilan (SPG) used clinically is a triple helix, we prepared alkali-denatured SPG (SPG-OH) as a single helix conformer. In this report, we measured the concentration of beta-glucan administered to mice by using a beta-glucan-specific reagent prepared from limulus amebocyte lysate (Gluspecy [G test], Seikagaku Corporation, Tokyo) and discuss the blood clearance of SPG and SPG-OH following intraperitoneal (i.p.) or intravenous (i.v.) administration. Comparing the clearance of SPG-OH from the blood with that of SPG, SPG-OH was removed faster than SPG following both i.p. and i.v. administration. This strongly suggests that the clearance of beta-glucans is dependent on their conformation.
The anti-tumor effects of recombinant human interleukin-2 (rIL-2) and sizofiran (SPG) were evaluated individually and in combination in C57BL/6 mice intraperitoneally inoculated with EL-4 lymphoma. The anti-tumor effects were evaluated by analysis of the intraperitoneal cell population in Giemsa-stained specimens, surface marker analysis of peritoneal exudative cells with flow cytometry, cytotoxic assay of cells against autologous tumor and Yac-1 lymphoma and a negative selection method, to identify the anti-tumor effector cells showing cytotoxic activity. The administration of SPG and/or rIL-2 reduced the lymphoma cells and proliferating lymphocytes, resulting in a decreased tumor/lymphocyte ratio in the order:control mice > SPG-treated mice > rIL-2-treated mice > rIL-2 plus SPG-treated mice. On day 5 after tumor inoculation, elevations in the number of L3T4+, Lyt2+, asialo GM1+ or Mac-1+ were demonstrated in the order:control mice < SPG-treated mice < rIL-2-treated mice < rIL -2 plus SPG-treated mice. The cytotoxic activity of peritoneal exudative cells against autologous tumor and the NK (natural killer) activity were increased in the same order. The anti-tumor effector cells which showed cytotoxic activity against autologous tumor cells were cytotoxic T lymphocytes, NK cells and cytotoxic macrophages. In the mice treated with SPG and rIL-2 plus SPG, especially, cytotoxic macrophages were shown to be the main anti-tumor effector cells. On day 10 after the inoculation, both a marked reduction in Lyt2+ lymphocytes and an elevation of L3T4+ lymphocytes were observed in all groups of mice. NK cells and cytotoxic macrophages were thought to be the main effector cells against autologous tumor, but their cytotoxic activities were lower than those examined on day 5. It was demonstrated that the administration of SPG and/or rIL-2 to the EL-4 lymphoma-bearing mice activated immune response cells in the peritoneal cavity such as T lymphocytes, NK cells or macrophages, which caused a reduction in lymphoma cells. The combination rIL-2 and SPG therapy was shown to activate the anti-tumor immune response at the tumor site more effectively than when either agent was administered alone.
Treatment of squamous cell carcinoma (SCCVII) bearing mice with the immunostimulant schizophyllan (SPG) raised the relative content of Mac-1 positive host cells infiltrating the tumor and increased photofrin retention in these tumors. In vitro colony formation assay following photofrin-based photodynamic therapy (PDT) in vivo revealed a greater killing of tumor cells in the SPG pre-treated group, particularly pronounced when the tumor excision was delayed for 8 h after PDT. The tumor cure rate increased approximately three times when PDT was preceded by the SPG therapy. In contrast, the administration of SPG after PDT was of no benefit for tumor control.