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Medicinal Value of Turkey Tail Fungus Trametes versicolor (L.:Fr.) Pilat (Aphyllophoromycetideae). A Literature Review
Abstract
Trametes (=Coriolus) versicolor (L.:Fr.) Pilát, is a small, flexible polypore fungus that is an important part of the forest ecology as a recycler of dead and dying trees in forests throughout the world. Of all the mushrooms used today for their medicinal qualities, more research has been performed on this species than any other, including shiitake (Lentinus edodes), or reishi (Ganoderma lucidum).High-molecular-weight fractions from the mycelium have been studied in human clinical trials, especially polysaccharide Krestin (PSK), which is an approved drug paid for by national health care in Japan. PSK is given orally (often 3 grams/day), along with several chemotherapy protocols. Numerous in vitro and in vivo studies show enhancement of immune functions, antiviral effects, and cholesterol-regulating effects, among others. New clinical trials demonstrate improved quality of life after surgery and in combination with chemotherapy, as well as extended 5- and 10-year survival rates, especially for patients with colorectal and stomach cancers. Further studies are needed in order to clarify the most effective forms of the whole fruiting body extracts, mycelium extracts, and their high-molecular weight fractions, along with the optimum dose. Safety issues, while not completely determined for long-term treatment, during pregnancy, or in combination with pharmaceutical drugs, seem to be of low concern, with no noted published side effects or interactions with drugs reported.
... Since prehistoric times, and across different civilizations, mushrooms have been utilized as a dietary source and in medication [1]. Mushrooms possess bioactive constituents that are antioxidant, anti-inflammatory, immunomodulatory, and antidiabetic [2][3][4][5]. There are several mushrooms whose polysaccharides have been well characterized by biophysical and biochemical techniques, and their bioactivities show promise for different diseases [4,5]. ...
... Mushrooms possess bioactive constituents that are antioxidant, anti-inflammatory, immunomodulatory, and antidiabetic [2][3][4][5]. There are several mushrooms whose polysaccharides have been well characterized by biophysical and biochemical techniques, and their bioactivities show promise for different diseases [4,5]. Among these, Ganoderma, Trametes or Coriolus (commonly known as Turkey tail), Lentinus, Morchella, and several other genera have displayed both nutritional and medicinal properties [6]. ...
... A polysaccharopeptide obtained from a strain of the Coriolus species in China also had anticancer and immune-boosting properties [9]. In Japan, for cancer treatment, a few grams of PSK is given orally to patients during chemotherapy [4]. Different biological test results of PSK showed improvement of immune functions, antiviral defense, body regulation of cholesterol, and prebiotic activity [4,13]. ...
Mushroom polysaccharides are active medicinal compounds that possess immune-mod-ulatory and anticancer properties. Currently, the mushroom polysaccharides krestin, lentinan, and polysaccharopeptides are used as anticancer drugs. They are an unexplored source of natural products with huge potential in both the medicinal and nutraceutical industries. The northern parts of Pakistan have a rich biodiversity of mushrooms that grow during different seasons of the year. Here we selected an edible Morchella esculenta (true morels) of the Ascomycota group for polysaccharide isolation and characterization. Polysaccharopeptides and polysaccharides from this mushroom were isolated using the green chemistry, hot water treatment method. Fourier transform infrared spectroscopy revealed the sugar nature and possible beta-glucan type structure of these polysac-charides. Antioxidant assays showed that the deproteinized polysaccharides have moderate free radical scavenging activity. These isolated polysaccharides exhibited good acetylcholinesterase (AChE) and butyryl cholinesterase (BChE) inhibition activities. Therefore, these polysaccharides may be valuable for the treatment of Alzheimer's and Parkinson's diseases. Further bioassays are needed to discover the true potential of M. esculenta polysaccharides for medicinal purposes.
... Since prehistoric times, people from many different cultures have eaten mushrooms and used them as medicine (1). Antioxidants, antiinflammatory, antimutagenic, and anti-diabetic bioactive components have been found in mushrooms (2)(3)(4)(5). Biophysical and biochemical approaches have provided a detailed description of the polysaccharides in a number of mushrooms whose bioactivities hold promise for the treatment of a wide range of illnesses (2,5). ...
... Antioxidants, antiinflammatory, antimutagenic, and anti-diabetic bioactive components have been found in mushrooms (2)(3)(4)(5). Biophysical and biochemical approaches have provided a detailed description of the polysaccharides in a number of mushrooms whose bioactivities hold promise for the treatment of a wide range of illnesses (2,5). ...
... Firstly, Hobbs (2004) showed that T. versicolor contained triterpenoid sterols as ergosta-7,22-dien-3β-ol, as well as fungisterol and β-sitosterol. In the 2010s Kamiyama et al. (2013) characterized 73 compounds from the extracts of T. versicolor as 16 alkyl esters, acetals, and lactones, 15 alkyl acids, 14 heterocyclic compounds, 11 alkyl alcohols, 9 alkyl aldehydes and ketones, and 8 aromatic compounds. ...
... In addition, it is the most commonly used fungus for various cancers and affects the lungs, esophagus, breast, cervix, uterus, leukemia, lymphoma (lymphatic tissue that causes swollen nodes), melanoma (skin cancer), brain cancer, usually under the abdominal button. When metastases occur (Hobbs 2004). Polysaccharide-K has a broad spectrum of mechanism of action: 1) stimulates the immune system of the body, inhibits the growth and development of adenosarcoma, fibrosarcoma, mastocytoma, plasmacytoma, melanoma, sarcoma, carcinoma, lung and breast cancer, leukemia, adenocarcinoma, cancer of the liver, stomach, larynx. ...
Trametes betulina (L.) Pilát.; Trametes cinnabarina (Jacq.) Fr.; Trametes gibbosa (Pers.) Fr.; Trametes hirsuta (Wulfen) Lloyd; Trametes pubescens (Schumach.) Pilát; Trametes suaveolens (L.) Fr.; Trametes versicolor (L.) Lloyd - POLYPORACEAE
... The use of generally recognized as safe (GRAS) medicinal mushrooms already authorised for human consumption by the U.S. Food and Drug Administration (FDA), such as Basidiomycetes, have significant potential as immunostimulants for farmed fish. More particularly, a plethora of bioactive compounds have been isolated from Ganoderma lucidum (reishi) and Trametes versicolor (turkey tail, also referred as Coriolus versicolor), including polysaccharides, triterpenes, ganoderan and ganodermin; or protein-bound polysaccharides (PSK) and polysaccharopeptides (PSP) respectively [4][5][6][7]. Indeed, these have been involved in different biological activities, for instance antioxidant, anticancer, anti-inflammatory, hepatoprotective or immunomodulatory functions [8][9][10][11][12][13]. Such immunostimulant properties have already been demonstrated in terrestrial animals, humans or cellular models [5,6,[14][15][16], however to date only a few studies have investigated the effect of dietary supplementation of these both mushrooms and/or their extracts for aquaculture applications in crustaceans [17,18] and fish [17,19,20]. ...
... Indeed, these have been involved in different biological activities, for instance antioxidant, anticancer, anti-inflammatory, hepatoprotective or immunomodulatory functions [8][9][10][11][12][13]. Such immunostimulant properties have already been demonstrated in terrestrial animals, humans or cellular models [5,6,[14][15][16], however to date only a few studies have investigated the effect of dietary supplementation of these both mushrooms and/or their extracts for aquaculture applications in crustaceans [17,18] and fish [17,19,20]. ...
Misuse and overuse of antibiotics in aquaculture has proven to be an unsustainable practice leading to increased bacterial resistance. An alternative strategy involves the inclusion of immunostimulants in fish diets, especially fungal and herbal compounds already authorized for human consumption, hence without environmental or public health concerns. In this study, we used a holistic and cross-disciplinary pipeline to assess the immunostimulatory properties of two fungi: Trametes versicolor and Ganoderma lucidum; one herbal supplement, capsaicin in the form of Espelette pepper (Capsicum annuum), and a combination of these fungal and herbal additives on rainbow trout (Oncorhynchus mykiss). We investigated the impact of diet supplementation for 7 weeks on survival, growth performance, cellular, humoral, and molecular immune parameters, as well as the intestinal microbial composition of the fish. Uptake of herbal and fungal compounds influenced the expression of immune related genes, without generating an inflammatory response. Significant differences were detected in the spleen-tlr2 gene expression. Supplementation with herbal additives correlated with structural changes in the fish intestinal microbiota and enhanced overall intestinal microbial diversity. Results demonstrated that the different treatments had no adverse effect on growth performance and survival, suggesting the safety of the different feed additives at the tested concentrations. While the mechanisms and multifactorial interactions remain unclear, this study provides insights not only in regard to nutrition and safety of these compounds, but also how a combined immune and gut microbiota approach can shed light on efficacy of immunostimulant compounds for potential commercial inclusion as feed supplements.
... The study of the antiviral activity of mushrooms was started in the second half of the 20th century and was reported for the first time from an extract of the mushroom Lentinula edodes [49]. In 1977, the Ministry of Japan approved the polysaccharides (PSK) fraction obtained from Trametes versicolor, and by 1987, the fraction accounted for 25.2% of the total expenditure for the manufacturing of anticancerous agents [56]. [60]. ...
... The study of the antiviral activity of mushrooms was started in the second half of the 20 th century and was reported for the first time from an extract of the mushroom Lentinula edodes [49]. In 1977, the Ministry of Japan approved the polysaccharides (PSK) fraction obtained from Trametes versicolor, and by 1987, the fraction accounted for 25.2% of the total expenditure for the manufacturing of anticancerous agents [56]. In contrast, Liu et al. revealed that PSK can inhibit the growth of B cells and activate natural killer cells and T cells in EBV (Epstein-Barr virus)-infected blood lymphocytes of the umbilical cord and exert increased cytotoxicity against B cells infected with EBV [57]. ...
It is well known that the utilization of mushrooms as therapeutic agents is not new. Over the past years, they are used by the local individuals as food as well as medicines, throughout the world. Nowadays, mushrooms are excessively used in medicine, pharmacy, food, and fermentation fields, as well. Wild mushrooms are of particular interest, especially Trametes versicolor (commonly known as turkey mushrooms) due to their various uses in the food and pharmaceutical industries. They represent not only a huge storehouse of vitamins, minerals, and dietary fiber, but they are also an important source of bioactive polysaccharides. They are widely used in traditional oriental therapies. The fruiting bodies are used in the preparation of health tonics and tea. The present review is necessary to explore more about this mushroom-like classical taxonomy, morphology, nutritional value, bioactivity, various health attributes, mechanism of bioactive components against various diseases, and food applications. The influence of processing processes on the nutritional properties and bioactivity of the fungus is discussed. Potential bioactive components, promising health attributes of Trametes versicolor have been extensively described. Besides, several in vivo and in vitro studies have demonstrated beneficial effects of polysaccharopeptides (PSP) and Polysaccharide-K (PSK) on aspects related to immune function and inflammation, also presenting an anti-cancerous effect. Moreover, PSP and PSK were successfully described to decrease several life-threatening diseases. Potential food applications of Trametes versicolor were detailed to signify the effective utilization of the mushroom in functional food formulation.
... Coriolus versicolor (L.) Quél. which is now known by its accepted scientific name as Trametes versicolor (L.) Lloyd (family Polyporaceae) is the most common wood rotting species on dead hardwoods (Hobbs 2004). This species, whose folk names are Turkey Tail in western cultures, Yun-Zhi (cloud-like mushroom) in China, or Kawaratake (mushroom by the river bank) in Japan, is thought to have had a long history of use in traditional medicine, particularly in Asia (Chu et al. 2002;Hobbs 1995). ...
... This species, whose folk names are Turkey Tail in western cultures, Yun-Zhi (cloud-like mushroom) in China, or Kawaratake (mushroom by the river bank) in Japan, is thought to have had a long history of use in traditional medicine, particularly in Asia (Chu et al. 2002;Hobbs 1995). Turkey tail is one of the most potent and the best studied of all medicinal mushrooms, including shiitake (Lentinus edodes), and reishi (Ganoderma lucidum) (Hobbs 2004). Two polysaccharides, polysaccharopeptide (PSP) and Polysaccharopeptide Krestin (PSK), isolated from T. versicolor are effective immunostimulants which are used to supplement chemotherapy and radiotherapy of cancers and various infectious diseases (Habtemariam 2020;Jiménez-Medina et al. 2008). ...
Today mankind confronts a heap of challenges for survival due to the advent of health-related issues, drug resistances, and imbalances in the ecosystems. In the era of technology, man has perpetually been endeavoring to search for diverse biotic components that can potentially be addressing the complicated life troubling issues. In this context, the fungi in general and mushrooms in particular have played an indispensable role in protecting and curing various health problems. Macrofungi or mushrooms are contemplated as biological and genetic resources with high nutritional, medicinal, and biotechnological potential. The interest in mushrooms has cultivated momentously in the last few decades, being promoted by the discovery of a repertoire of chemically disparate biologically active compounds having biopharmaceutical applications arbitrated through defined mechanisms (anti-tumor, anti-inflammatory, anti-cancer, anti-oxidative hepatoprotective, anti-viral, immunomodulating hypocholesterolemic, and anti-bacterial). The escalating knowledge about chemistry, biotechnology, and molecular biology of mushrooms as well as an improvement in screening methods has led to rapid surge in the application of mushrooms for medicinal purposes which in turn, have galvanized the development of several novel mycopharmaceuticals based on mushroom bioprospection. Taking into consideration the importance of mushrooms, this chapter aims to zero in on the nutritive value, functionalities of mushrooms, and potential applications in food industry.
... Japonya ve Çin'de binlerce yıldır ilaç olarak tanınmaktadır. 25 Batı dünyasındaki en yaygın adı ise Hindi Kuyruğu'dur ve farklı morfolojik özellikleri, başlığın üst tarafındaki (sapsız) eş merkezli çok renkli bölgeleri ve alt taraftaki spor içeren poliporları içerir. Mantar, tüm bölgelerinde kaydedildiği Birleşik Krallık da dahil olmak üzere ılıman Asya, Kuzey Amerika ve Avrupa'da yaygındır. ...
... 5 yıl içinde kanserden ölüm oranı PSK ile %21, olmadan %52 idi. 25 Yapılan bir çalışmada polisakkaritler insan yumurtalık kanseri hücreleri üzerindeki sitotoksisiteyi arttırdığı; lipit peroksit ve süperoksit dismutaz enzim aktivitesinde cisplatin kaynaklı değişiklik üzerindeki hücreye bağlı etkiyi modüle ettiği belirtilmiştir. 29 ...
Mantarlar, içerdikleri biyoaktif özellikteki maddeler ile gıda, ilaç ve kozmetik sanayisinde önemli bir doğal kaynak olarak kullanılabilmektedir. Ayrıca insan sağlığı üzerine bilinen etkileri nedeniyle uzun yıllardan beri halk arasında geleneksel tedavide kullanıldığı bilinmektedir. Çalışmamızda; jinekolojik kanserlerde kullanılan destek tedavilerden biri olan mantar kullanımının, etkilerinin ve tedavi sürecinde oluşabilecek risklerin güncel literatür kapsamında irdelenmesi amaçlanmıştır.Oldukça zor olan kanser hastalıklarının tedavi ve önleme sürecinde en çok önerilen yaklaşımlarından biri, benzersiz biyoaktif ikincil metabolitleri içerdikleri için bitki veya kullanılabilir mantar materyallerinin sık tüketilmesidir. Özellikle onkoloji alanında tedavi sürecinde kemoterapi ve radyasyonun olumsuz etkilerini azaltarak, yaşam kalitesini iyileştirerek hastaların süreci daha rahat geçirebilmelerini sağlamak amacıyla kullanılırlar. Mantar ekstraktları ile yapılan çalışmalar mantarların ve mantar ekstraktlarının koruyucu, güvenli ve genellikle de iyi tolere edilebilir düzeyde olduğunu göstermektedir. Mantarların veya mantar ekstraktlarının servikal, over ve endometriyal kanser üzerine etki mekanizmalarıyla ilgili yapılan çalışmalarda apoptozisi arttırdığı, over kanser oluşumunu engellediği ve sağkalım artışına destek olduğunun belirtildiği birçok çalışma bulunmaktadır. Bununla birlikte kanser hastalarında, özellikle bitkisel kaynaklı destek tedavi kullanımının ilaç etkileşimlerine neden olabildiği ve bu bitkilerin tedaviyi olumsuz etkileyebildiği de belirtilmektedir. Sonuç olarak jinekolojik kanserlerde koruma veya tedavi etme amacıyla direkt ya da indirekt yolla kullanılabilen mantarların hastalık sürecine etkileri göz ardı edilmemelidir ancak sağlık profesyonelleri ile kontrol altında tutulmalıdır.
... Moreover, A. blazei mycelium cultivated in liquid cultures excretes an extracellular antitumor proteoglycan with high molecular weight (1000-10,000 kDa), which was composed of mannose, glucose, galactose, and ribose groups [102]. One of the most successful therapeutic mushroom polysaccharides, which has been marketed as an anticancer drug (in combination with chemotherapy), krestin (polysaccharide-K, PSK) derives from the edible mushroom Coriolous versicolor (Trametes versicolor) [103]. It is a lowmolecular-weight proteoglycan, containing glucose as a major monosaccharide, but other sugar residues are also present, such as mannose, fucose, xylose, and galactose. ...
... It is a lowmolecular-weight proteoglycan, containing glucose as a major monosaccharide, but other sugar residues are also present, such as mannose, fucose, xylose, and galactose. The main chain of PSK is made of β-(1,4)-glucopyranoside, with β-(1,6)-glucopyranosidic sidechains at every fourth glucose unit [103,104]. Another source of therapeutic (immunomodulatory and antidiabetic) polysaccharides is the edible medicinal Tremmella mushrooms. Tremella polysaccharides are composed of a linear backbone of α-(1,3)-D-rhamnose, with side groups of xylose and glucuronic acid. ...
Selenosugars are a group of sugar derivatives of great structural diversity (e.g., molar masses, selenium oxidation state, and selenium binding), obtained as a result of biosynthesis, chemical modification of natural compounds, or chemical synthesis. Seleno-monosaccharides and disaccharides are known to be non-toxic products of the natural metabolism of selenium compounds in mammals. In the case of the selenium-containing polysaccharides of natural origin, their formation is also postulated as a form of detoxification of excess selenium in microorganisms, mushroom, and plants. The valency of selenium in selenium-containing polysaccharides can be: 0 (encapsulated nano-selenium), IV (selenites of polysaccharides), or II (selenoglycosides or selenium built into the sugar ring to replace oxygen). The great interest in Se-polysaccharides results from the expected synergy between selenium and polysaccharides. Several plant- and mushroom-derived polysaccharides are potent macromolecules with antitumor, immunomodulatory, antioxidant, and other biological properties. Selenium, a trace element of fundamental importance to human health, has been shown to possess several analogous functions. The mechanism by which selenium exerts anticancer and immunomodulatory activity differs from that of polysaccharide fractions, but a similar pharmacological effect suggests a possible synergy of these two agents. Various functions of Se-polysaccharides have been explored, including antitumor, immune-enhancement, antioxidant, antidiabetic, anti-inflammatory, hepatoprotective, and neuroprotective activities. Due to being non-toxic or much less toxic than inorganic selenium compounds, Se-polysaccharides are potential dietary supplements that could be used, e.g., in chemoprevention.
... A white rot fungus, T. versicolor is among the only organisms known to completely digest lignin (van der Wal et al. 2015), with the resulting wood becoming soft and spongy with a whitish color (Gao et al. 2010). Trametes versicolor also has welldocumented medicinal properties, which include antitumor, antimicrobial, immune-enhancing, antioxidant, and antiradical compounds (Chu et al. 2002;Hobbs 2004;Janjušević et al. 2017), as well as the ability to degrade several organic pollutants (Gao et al. 2010) and herbicides (da Silva Coelho-Moreira et al. 2013). ...
... Used medicinally for centuries, fruit bodies can be consumed in teas and soups. Wild strains have been shown to inhibit tumor growth and are used to treat a wide variety of cancers (Hobbs 2004). Research has shown that T. versicolor boosts the immune system by increasing natural killer cells, contains antiviral agents that may inhibit HIV replication, and has strong antibiotic compounds effective against several human pathogens (Chu et al. 2002). ...
Glossy privet ( Ligustrum lucidum W. T. Aiton) is a highly aggressive tree that has become globally invasive in a wide range of habitats and can quickly form dense thickets, shading and outcompeting native vegetation. Slowly decomposing slash following removal of dense infestations can create additional management challenges, including fire risk concerns, which curtailed planned invasive plant removal projects on certain tracts within the Balcones Canyonlands Preserve near Austin, TX. This prompted a pilot study to explore whether wood-decaying fungi could be used to hasten the recycling of L. lucidum logs back into the forest ecosystem. We inoculated 25 freshly cut L. lucidum logs with Trametes versicolor (Fr.) Pilat at two study sites and monitored the inoculated logs and 5 untreated control logs over a 3-yr period (February 2015 to March 2018). We found that inoculation significantly accelerated wood decay. By the end of our study, 100% of logs with >3 inoculation points were in advanced stages of decay, while only one of the control logs showed noticeable signs of decay. Inoculating logs in the field was easy and suitable for novices, requiring little or no previous experience to achieve successful results. An added benefit of using T. versicolor is its medicinal properties and potential for bioremediation. We have continued to inoculate logs with comparable success and are integrating them into forest restoration projects. Applied on a larger scale, these wood-decaying fungi have the potential to transform nonnative deadwood from a threat to an asset.
... The powder evaluated in this work contained 55% (w/w) carbohydrate and 25% (w/w) protein. Traditional preparations of medicinal species, used for thousands of years, might give some support to the idea that a heat-treatment might preserve at least part of the activity [30]. ...
... The higher index obtained for aqueous extract could be related with the presence in this fraction of immunostimulating glucans. It has been reported that hydroalcoholic extracts are likely to have less activity, partly because the high-molecular weight compounds are precipitated by alcohol and may not go into solution [30]. ...
Since the potentiation of host resistance is one of the most important objectives in cancer and AIDS therapy, the present study examined the immunomodulating effects of Pleurotus sp. fruiting bodies powder on cyclophosphamide (CY) treated mice. Pleurotus powder was administered during 7 days to Balb/c mice by oral route (1000 mg/kg) and the CY (100 mg/kg) was inoculated intraperitoneally, at the beginning of the experiment or at the fifth day. The influence of the supplement on CY immunosuppresion was evaluated on the eighth day. The prophylactic administration of Pleurotus powder increased the bone marrow cellularity (9.89 x10 6 vs. 4.94 x 10 6 per femur in therapeutically treated mice, p=0.035) and the white blood cell counts (7.8 x10 9 vs. 4.7 x10 9 cells/L, p=0.016). The Pleurotus supplement in the prophylactic treatment stimulated the liver protein synthesis; although no significant effects were found in serum protein concentrations. The effect of Pleurotus powder on cell-mediated immunity was determined by the delayed-type hypersensitivity reaction (DTH) in mice under the therapeutic schedule. The DTH response measured at 48 and 72 h after antigen challenge was similar that of normal control mice (p< 0.05). The induction of DTH reaction was associated with an increase in the mass index of popliteal lymph nodes (p= 0.044). An in vitro lymphoproliferative-stimulating response evaluated in mice spleen cells was also demonstrated with aqueous and ethanolic extracts obtained from Pleurotus powder. These effects suggest that Pleurotus supplement could potentiate the host defense mechanisms in vivo and should be promising for further pharmacological studies.
... Reducing sugars are structural constituents of beta-D-glucans, components of mycetes' cell walls with a well-documented immunity-stimulating effect [33]. On the other hand, amino acids are the structural units of proteins that may be associated to polysaccharides to form immunomodulating complexes, like PSP isolated from the mycelium of Trametes versicolor [34]. Moreover, fungal immunomodulatory proteins, purified from medicinal mushrooms comprise a group of novel proteins which possess immunomodulatory properties and have a strong potential of being applied to food or pharmaceutical products for commercial development [35]. ...
Mushroom science in Cuba allows the valorization of agricultural by-products into functional foods/nutraceuticals for human consumption to address objectives of sustainability and biotechnological development. Much research work done in Cuban eastern region has been performed on the Pleurotus genus, whose cultivation has increased greatly during the last few decades. Pleurotus species, like many edible and medicinal mushrooms, are a good source of immunomodulators and "host defense potentiators" (HDPs). In this context, dietetic supplements with a high therapeutic potential acting on the immune system and formulated from refined or partially refined mushroom extracts, or from dried mycelia/fruiting bodies biomass are referred as "mushroom immunoceuticals". The present study examined the synergy exerted by the structural diversity of biomolecules found in Pleurotus crude extracts and powders on immune responses of both immunocompetent and immunodeficient Balb/c mice. Pleurotus derived-products could potentiate the host defense mechanisms in vivo and should be promising for further pharmacological studies. The effects on cell immunity are especially valuable in the prophylaxis of tumors, immunodeficiencies and as co-adjuvant in chemotherapy. The results also demonstrate that not only mushrooms but also their mycelia may be a good candidate for nutraceuticals production. Through this immunological "window" we are assisting to a revolution in mushroom science characterized by the diversity of compounds found in mushrooms and on the other hand, by the possibilities given by the abundance of specific molecular targets. An extended knowledge of the immuno-enhancing activity of Pleurotus nutraceuticals would be useful in understanding their potential applications for immunonutrition and immunotherapy.
... Fruit bodies of another polypore, Fomitopsis pinicola are dried and applied to wounds to stop bleeding (Rogers, 2012). The species Trametes versicolor is reported to have good immunomodulating activities (Hobbs, 2004). According to Kobayashi et al. (1994), the presence of T. versicolor polysaccharopeptides increases in vitro anticancer activity of the chemotherapy drug, cisplatin. ...
... 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.
... T. versicolor (Turkey tail), one of the most precious medicinal mushrooms, has been the most actively studied mushroom in the last twenty years and is the source and producer of polysaccharide krestin (PSK) and polysaccharide peptide (PSP). Also, T. versicolor has been reported to possess a great number of bioactive properties such as anticancer, antitumor, hepatoprotective, immunomodulating, antioxidant, antibacterial, anticholinesterase, and cardiovascular effects [10]. T. pubescens is an important mushroom used in Asian countries to treat gastrointestinal diseases and cancer in folk medicine [11]. ...
Trametes genus is one of the most important medicinal mushroom species in the world. The present study focused on phenolic profile, cholinesterase inhibitory and antioxidant activities of four Trametes species (T. bicolor, T. pubescens, T. suaveolens and T. versicolor). Phenolic profiles of the mushrooms were characterized by HPLC–DAD. ABTS·+ scavenging, β-carotene-linoleic acid, Cupric-reducing antioxidant capacity (CUPRAC), DPPH· scavenging, and metal chelating assays were performed to evaluate antioxidant activities of the extracts. Ellman method was used to test butyrylcholinesterase (BChE) and acetylcholinesterase (AChE) inhibitory activities of the extracts. The most abundant compound was fumaric acid (4.51 ± 0.10 µg/g) in T. bicolor, trans-cinnamic acid (0.49 ± 0.05 µg/g) in T. pubescens, catechin hydrate in T. suaveolens (0.92 ± 0.16 µg/g) and T. versicolor (0.96 ± 0.19 µg/g). T. pubescens acetone extract showed the highest antioxidant activity in CUPRAC (A0.50: 19.26 ± 0.21 µg/mL), ABTS·+ (IC50: 3.55 ± 0.16 µg/mL), DPPH· (85.12 ± 0.44%), β-carotene-linoleic acid (IC50: 1.12 ± 0.41 µg/mL) assays. The best metal chelating activity was found in T. versicolor hexane extract (56.78 ± 0.63%). It was determined that T. pubescens hexane extract (IC50: 7.37 ± 0.55, 15.24 ± 0.98 µg/mL, respectively) showed higher AChE and BChE inhibitory activities. The results of this study support the potential use of Trametes species to design new functional drug formulations.
... Trametes is traditionally consumed, popular medicinal mushrooms that have been used particularly in Asian countries from ancient times to improve longevity and health [35][36][37]. There are a number of research publications that report the abundance and variety of biological actions led by the primary metabolites of Trametes such as polysaccharides, proteins and sterols [36][37]. ...
Species of Trametes are important wood decomposers in natural ecosystems and they have been widely used as traditional medicines in Asia. In order to assess the fungal biodiversity of the Greater Mekong Subregion, surveys of Trametes were conducted in Laos. In this paper, Trametes cubensis is introduced as a new record from Laos based on morphology and molecular evidence. The collected specimens are described with colour photographs and illustrations, and compared with similar taxa. A phylogenetic analysis for the new collection of T. cubensis is provided based on ITS, LSU and TEF1 sequence data and the taxonomic status of the species is briefly discussed. Furthermore, the bioactive compounds, beneficial properties and biotechnological applications of Trametes species are also reviewed.
... The polysaccharide Crestin from T. versicolor is an even more widespread and better studied immunomodulator compared to PSP [33]. Of all the fungi used today because of their medicinal properties, more research has been conducted on this species than any other, including Lentinus edodes, or Ganoderma lucidum [34]. ...
... The polysaccharide Crestin from T. versicolor is an even more widespread and better studied immunomodulator compared to PSP [33]. Of all the fungi used today because of their medicinal properties, more research has been conducted on this species than any other, including Lentinus edodes, or Ganoderma lucidum [34]. In the period 2005-2007, five more PSK studies [35], [36] on colorectal cancer [37] were published, including one meta-analysis with 1,094 patients and all have had positive responses to clinical treatment [38]. ...
... Lloyd (= Coriolus versicolor, Polyporaceae, Agaricomycetes), represents a good source of components with antioxidant and antibacterial properties such as extracellular and intracellular polysaccharopeptides. [10][11][12] T. versicolor commercial preparations produced by deep-layer mycelium cultivation, i.e., krestin (PSK) and polysaccharopeptide (PSP) are already present on the market. 13 Additionally, our previous research confirmed significant antibacterial activity of T. versicolor crude exopolysaccharides (cEPS) isolated after submerged cultivation in stirred-tank bioreactor. 14 The objective of this study was to analyze antioxidative potential and perform additional chemical characterization of isolated cEPS to elucidate its composition and to determine its potential for application as a natural antioxidative food additive, as well as a natural taste and aroma enhancer. ...
Crude Trametes versicolor exopolysaccharides (cEPS) were used for antioxidative activity testing. Obtained results revealed high ability of cEPS for DPPH free radical scavenging and high chelating ability at the highest tested concentration (20 mg/mL), while the reducing power was significantly lower. However, based on the EC50 values, antioxidative activities of the cEPS decreased in the following order: reducing power > DPPH scavenging ability > chelating ability. Due to the high carbohydrate and β-glucan content it is assumed that they are the main carriers of cEPS antioxidative activities. D-glucose was the main monosaccharide (87.18 ± 0.27%) while the dominant amino acids were L-lysine (L-glutamic and L-aspartic acid), which are amino acids with taste similar to the monosodium glutamate. In addition, content of sweet tasting amino acids compared with the group of bitter tasting amino acid was 2.1 times higher, indicating favorable composition of cEPS protein fraction for food industry applying.
... In 1977, Health ministry of Japan gave approval to a polysaccharide (PSK-Polysaccharide Krestin) isolated from Trametes Versicolor to be used as an anticancer agent in human (Hobbs 2004). In a study carried in 2008, Trametes versicolor was orally administered in women with breast cancer as part of Phase I trial and a promising observation was made. ...
Mushrooms are macroscopic fungi which can be either epigeous or hypogeous and is estimated to be 140,000 on earth, yet only 10% are known. Since ancient time, it played a diverse role in human history for mycolatry, mycophagy and as medicine in folklore and religion. Many Asian and western countries consider mushrooms as panacea for a large number of diseases and utilized for consumption as a gourmet food for its taste as well as flavor. In recent years, scientific research fraternities have confirmed that various extracts and metabolites of mushrooms used traditionally are able to treat a wide range of diseases due to their balanced modulation of multiple targets thereby providing a greater therapeutic effect or equivalent curative effect to that of modern medicine. Medicinal mushrooms especially those belonging to higher basidiomycete groups are reservoir of bioactive compounds with multiple therapeutic properties. The present review provides historical importance as well as an updated information on pharmacologically relevant higher basidiomycetes belong to the genus Agaricus, Auricularia, Phellinus, Ganoderma, Pleurotus, Trametes and Lentinus and their biologically active secondary metabolites. This will help the researchers to understand various type of secondary metabolites, their therapeutic role and related in vivo or in vitro work at a glance. The mounting evidences from several scientific community across the globe, regarding various therapeutic applications of mushroom extracts, unarguably make it an advance research area worth mass attention.
... In 1977, Health ministry of Japan gave approval to a polysaccharide (PSK-Polysaccharide Krestin) isolated from Trametes Versicolor to be used as an anticancer agent in human (Hobbs 2004). In a study carried in 2008, Trametes versicolor was orally administered in women with breast cancer as part of Phase I trial and a promising observation was made. ...
This study investigates the hepatoprotective effect of a water-alcohol extract of the medicinal mushroom Phellinus caryophylli (Racib.) G. Cunn. (PCE) against acetaminophen (APAP)-induced hepatotoxicity in Swiss albino mice. The mice orally received APAP (150 mg/kg body weight), followed by PCE extract (250 or 500 mg/kg body weight). The liver damage induced by APAP was analyzed on the basis of blood serum parameters (glutamate pyruvate transaminase, glutamate oxaloacetate transaminase, and alkaline phosphatase), antioxidant assays (reduced glutathione and glutathione peroxidase), and tissue peroxidation based on malondialdehyde level. The molecular mechanism underlying the prevention of APAP-induced damage by PCE was also analyzed. Liver damage was confirmed on the basis of increased serum parameter values, decreased antioxidant levels, and cellular and molecular alterations, which PCE restored in a dose-dependent manner. At a transcriptional level, PCE downregulated expression of the preapoptototic gene Bax and the inflammatory gene Cox2 but upregulated the antiapoptotic gene Bcl2 in the mice that received APAP. PCE exerted a hepatoprotective effect by preventing apoptotic and inflammatory events caused by APAP. Thus, this study demonstrates a hepatoprotective effect of PCE, which could be explored further for managing hepatopathy.
... It was reported that the polysaccharide peptide krestin from T. versicolor can be potentially used as an adjuvant in preventing breast cancer. 33 This polysaccharide manifested antiproliferative activity in vitro and in vivo against the human QGY hepatocarcinoma cancer cell line by inhibiting its growth at concentrations below 20 µg · mL −1 , with a half-maximal inhibitory concentration as low as 4.25 µg · mL −1 . ...
We analyzed the antiproliferative activity of 6 medicinal wood-destroying mushrooms (Fomes fomentarius, Fomitopsis pinicola, Trametes versicolor, Trichaptum biforme, Inonotus obliquus, and Coniophora puteana) that are common in deciduous and mixed coniferous forests in Central Russia. Morphological identification of strains collected from the wild was confirmed based on ribosomal DNA internal transcribed spacer phylogenetic analysis. We observed cytotoxic and cell growth–inhibitory effects of hot water extracts from mycelial biomass of 5 species—T. versicolor, C. puteana, F. fomentarius, F. pinicola, and I. obliquus—on leukemia cell lines (Jukart, K562, and THP-1); the effective extract concentrations were mostly less than 50 µg · mL⁻¹. However, we observed no antiproliferative activity of dry biomass from methanol–chloroform (1:1) extracts of C. puteana and F. fomentarius. A chemosensitivity assay showed that the most effective polypore mushroom extract was the methanol extract of T. versicolor (strain It-1), which inhibited the growth of 6 various solid tumors (A-549 and SWi573 [lung], HBL-100 and T-47D [breast], HeLa [cervix], and WiDr [colon]) at concentrations below 45 µg · mL⁻¹, with a concentration as low as 0.7–3.6 µg · mL⁻¹ causing 50% reduction in the proliferation of cancer cells in lung and cervix tumors. Methanol extracts of F. pinicola and I. obliquus were less effective, with proliferation-inhibiting capacities at concentrations below 70 and 200 µg · mL⁻¹, respectively. Thus, T. versicolor is a prospective candidate in the search for and production of new antiproliferative chemical compounds.
... Krestin , or polysaccharide - K ( PSK ) , is one of the most successful thera - peutic mushroom polysaccharides ( or polysaccharopeptide as it is often referred to ) that have been marketed as anticancer drugs ( in combination with chemotherapy ) and nutraceuticals . It derives from the edible mushroom Coriolous versicolor ( also known as Trametes versicolor ) ( Hobbs 2004 ) . Ooi and Liu ( 2000 ) reported that it is a low - molecular - weight ( 94 , 000 Da ) proteo - glucan containing 25 – 38% protein residues . ...
Mushrooms have been used for centuries in Asian and other traditional cuisine
and traditional medicines due to their culinary and medicinal properties,
but their properties remained unknown to the wide scientific community for
a long time. In the last few decades, a large amount of research has focused on
the types, sources, biosynthesis, and medicinal properties and applications of
many mushrooms, mainly members of the Basidiomycetes family. The most common active ingredients in these higher fungi are their extracellular,
intracellular, or cell wall polysaccharides, which exhibit immunostimulating,
antitumor, antimicrobial, anti-inflammatory, antioxidant, prebiotic, hypoglycemic,
and hypocholesterolemic effects. In the last few years, some of these
mushrooms or their biopolymers have been commercialized in pharmaceutical
applications, but their application in food and nutraceuticals is still at
an early stage. However, the fact that many of these mushrooms are edible
(and thus nontoxic) as well as tasty makes them, or their polysaccharides,
potentially ideal ingredients for the formulation of novel functional foods
and nutraceuticals. However, their biological properties might be affected
after addition to food, due to food processing and/or interaction with food
ingredients. This chapter describes the most important and studied types
and sources of bioactive mushroom polysaccharides, the biosynthesis and
bioprocess conditions used for the production/cultivation in solid or liquid
media, the relation between molecular/structural characteristics and bioactivity,
their medicinal properties, and their existing or potential applications
in human nutrition.
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... High molecular-weight fractions from the mycelium have been studied in human clinical trials, especially polysaccharide Krestin (PSK), which is an approved drug paid for by national health care in Japan. PSK is given orally (often 3 grams/day), along with several chemotherapy protocols (Hobbs 2004). "PSK", accounted for 25.2% of the total national expenditure for anticancer agents in Japan. ...
Tramete versicolor (known as "turkey tail") is one of the most potent, and the best studied, of all medicinal mushrooms. This mushroom is known to possess anti cancer, anti viral properties and stimulates the immune system. It is native to tropical, subtropical and temperate zones and is highly adaptive. No attempt had been made in India to cultivate this precious mushroom. T. versicolor was collected from Sampaje forest area of Coorg, Karnataka (Western ghats), India. It occurred as a classic bracket fungus with multicolored, closely concentric zonations with slightly hairy surface, the stem was central and short. Pure culture was made on MEA and the cultural requirements were studied. The ambient temperature and pH for the mycelial growth was 25°C and 4.5 to 6.0 respectively. The maximum mycelial growth was observed on MEA (14.93 mm/day), mycelium was pure white in color and moderately fluffy. The spawn was made on sorghum grain and the fructification was attempted on sawdust 90% + rice bran 10% substrate formulation. Spawn run was completed within 18-20 days at 25± 2°C. Fructification was observed at 25 ± 2°C and 80-85% R H. This is the first report of successful cultivation of T. versicolor from India. Successful cultivation of this mushroom will play a key role in the diversification of mushroom industry in India.
... Thus, L. deliciosus and C. cibarius seem to have a fine nutritive value besides their antioxidant properties. In vitro and in vivo studies have so far revealed that T. versicolor demonstrated anticancer, antitumor, anticarcinogenenic, and antiproliferative effects (Hobbs, 2004), whereas its ethanol extract did not exhibit remarkable anti-AChE and antioxidant activities in our assays, probably due to its low phenol content. ...
In the present study, we investigated the acetylcholinesterase (AChE) inhibitory activity of the ethanolic extracts of a number of mushroom species growing in Turkey, including mainly Polyporus species (Polyporus gilvus, Polyporus sulphureus, Polyporus annosus, Polyporus radiatus, Polyporus pinicola, Polyporus volvatus, Polyporus fomentarius, Polyporus stevenii, Polyporus badius), as well as Cantharellus cibarius, Lactarius deliciosus, and Trametes versicolor. The analyses were carried out using the spectrophotometric method of Ellman in ELISA microplate reader at 500μg/ml. Since Alzheimer's disease (AD) is associated with oxidative degeneration of cells, several methods of antioxidant activity were applied to the mushroom extracts such as 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity, ferrous ion-chelating effect, ferric-reducing antioxidant power (FRAP), and beta-carotene bleaching tests. Total phenol contents of the extracts were also determined by Folin–Ciocalteu reagent. In anti-AChE assay, the most active one was P. sulphureus having 31.44% of inhibition. P. voluatus showed the best scavenging effect against DPPH, while all of the extracts exerted low capacity in chelating ferrous ions and reducing ferric ion.
... Several polysaccharides with immunomodulatory and anticancer properties have been isolated from Trametes (Coriolus) versicolor (Mizuno, 1999). For instance, protein-bound polysaccharide Krestin (PSK) extracted from the mycelium of T. versicolor is prescribed for treatment of digestive system cancer (stomach, oesophagus, and colon) in Japan (Fukushima, 1989;Hobbs, 2004). PSK was the top-selling anticancer drug in Japan in 1987. ...
Analysis of genetic relationship of important Aphyllophorales germplasm accessions of the National Research Centre for Mushroom, Solan, India, was conducted using RAPD and ITS rDNA sequences. RAPD profiles exhibited significant variations among Trametes versicolor, Tyromyces chioneus, and Ganoderma species. The resulting RAPD-based phylogram grouped Ganoderma spp. accessions into four clades. Phylogeny inferred from ITS rDNA sequence distinguished Trametes versicolor, Tyromyces chioneus, and Ganoderma spp. at the generic level due to different lengths and variations of the 5.8S rDNA conserved region. At the intrageneric level, Ganoderma accessions were divided into two distinct groups based on nucleotide substitution in ITS-1 and ITS-2 regions. It is presumed that some of the Ganoderma sp. samples might be G. lucidum. Single nucleotide substitutions turned out to be more useful for genetic cataloguing of isolates within a species than sequence alignment using NCBI databse.
... Reducing sugars are structural constituents of beta-D-glucans, components of mycetes' cell walls with a well-documented immunity-stimulating effect (Rop, Mlcek, & Jurikova, 2009). On the other hand, amino acids are the structural units of proteins that may be associated to polysaccharides to form immunomodulating complexes, like PSP isolated from the mycelium of Trametes versicolor (Hobbs, 2004). Moreover, fungal immunomodulatory proteins, purified from medicinal mushrooms comprise a group of novel proteins, possess immunomodulatory properties and have a strong potential of being applied to food or pharmaceutical products for commercial development (Ou, Hsiao, Wang, Ko, & Lin, 2009). ...
This study examined the phytochemical profile and the effects of Pleurotus fruiting bodies powder on cell-mediated immune response in both in vivo and in vitro assays. Although carbohydrates (55%, w/w) appear to be the most important immunomodulatory compound, secondary metabolites (terpenoids, phenols and flavonoids) would also enhance immunity. Pleurotus powder was administered orally during 7 days to Balb/c mice (1000 mg/kg) and cyclophosphamide (CY; 100 mg/kg) was inoculated intraperitoneally at the beginning of the experiment. The delayed-type hypersensitivity reaction measured at 48 and 72 h after antigen challenge was similar to that of control mice and it was associated with an increase in the mass index of popliteal lymph nodes (p< 0.05). An in vitro lymphoproliferative-stimulating response was also demonstrated with aqueous and ethanolic extracts obtained from Pleurotus powder. These effects suggest that Pleurotus supplement could potentiate the cellular immune response and should be promising for further immunotherapy studies.
This comprehensive literature review delves into the multifaceted attributes of Trametes versicolor, commonly known as turkey tail mushroom. The turkey tail mushroom stands as a noteworthy source of diverse bioactive compounds with potent health benefits. This review offers a contemporary synthesis of its phytochemical constituents and their multifaceted impacts on human health. The mushroom's intricate composition, encompassing polysaccharides, phenols, and triterpenes, underpins its remarkable therapeutic potential. Focusing on key attributes such as anti-cancer, anti-microbial, and immunomodulatory activities, this review delves into the intricate mechanisms by which the turkey tail mushroom exerts its effects. In addition, the exploration extends to the enzymatic constituents inherent in the mushroom and their industrial significance. Mechanisms of action for both phytochemicals and enzymes are studied, providing a well-rounded understanding of their roles in conferring therapeutic and industrial benefits. This synthesis of research aims to provide an up-to-date perspective on turkey tail mushrooms' versatile applications. By intertwining the exploration of health benefits and enzymatic constituents, this review offers insights into the potential of harnessing this natural resource for innovative therapeutic strategies and industrial applications. Overall, it contributes to the advancement of knowledge and utilisation of turkey tail mushrooms' diverse properties for human health and industrial progress.
The environmental impact and denaturing propensity of organic solvents in the extraction of plant bioactives pose great challenges in extraction systems. As a result, proactive consideration of procedures and evidence for tuning water properties for better recovery and positive influence on the green synthesis of products become pivotal. The conventional maceration approach takes a longer duration (1-72 h) for product recovery while percolation, distillation, and Soxhlet extractions take about 1 to 6 h. An intensified modern hydro-extraction process was identified for tuning water properties with an appreciable yield similar to organic solvents within 10-15 min. The percentage yield of tuned hydro-solvents achieved close to 90% recovery of active metabolites. The additional advantage of using tuned water over organic solvents is in the preservation of the bio-activities and forestalling the possibility of contamination of the bio-matrices during extractions with an organic solvent. This advantage is based on the fast extraction rate and selectivity of the tuned solvent when compared to the traditional approach. This review uniquely approaches the study of biometabolite recovery through insights from the chemistry of water under different extraction techniques for the very first time. Current challenges and prospects from the study are further presented.
Thousands of organisms fall under the umbrella of fungal species, many with unique properties; some innocuous, some useful and some harmful.
This book covers the chemical composition and nutraceutical and pharmaceutical properties of edible fungi. It provides updates, future trends and perspectives on edible fungi, their nutritional properties, chemical features and different biological activities ascribed to them. Linking their functional use with different food products, it details the many health related properties of edible fungi. Phenolic acids, fatty acids, macromolecules, and different terpenes and steroids are presented as compounds with health improving properties. The book also discusses current technologies for mushroom cultivation and cultural use of mushrooms around the globe.
Intended for food scientists and technologists, this book offers insights into current research and developments on edible fungi and will stimulate additional research in this area. It could also be considered as a supplementary text for courses such as applied or medical mycology.
Background:
Mushrooms exist as an integral and vital component of the ecosystem and are very precious fungi. Mushrooms have been traditionally used in herbal medicines for many centuries.
Scope and approach:
There are a variety of medicinal mushrooms mentioned in the current work such as Agaricus, Amanita, Calocybe, Cantharellus, Cordyceps, Coprinus, Cortinarius, Ganoderma, Grifola, Huitlacoche, Hydnum, Lentinus, Morchella, Pleurotus, Rigidoporus, Tremella, Trametes sp., etc., which play a vital role in various diseases because of several metabolic components and nutritional values. Medicinal mushrooms can be identified morphologically on the basis of their size, color (white, black, yellow, brown, cream, pink and purple-brown, etc.), chemical reactions, consistency of the stalk and cap, mode of attachment of the gills to the stalk, and spore color and mass, and further identified at a molecular level by Internal Transcribed Spacer (ITS) regions of gene sequencing. There are also other methods that have recently begun to be used for the identification of mushrooms such as high-pressure liquid chromatography (HPLC), nuclear magnetic resonance spectroscopy (NMR), microscopy, thin-layer chromatography (TLC), DNA sequencing, gas chromatography-mass spectrometry (GC-MS), chemical finger printing, ultra-performance liquid chromatography (UPLC), fourier transform infrared spectroscopy (FTIR), liquid chromatography quadrupole time-of-flight mass spectrometry (LCMS-TOF) and high-performance thin-layer chromatography (HPTLC). Lately, the matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) technique is also used for the identification of fungi.
Key finding and conclusion:
Medicinal mushrooms possess various biological activities like anti-oxidant, anti-cancer, anti-inflammatory, anti-aging, anti-tumor, anti-viral, anti-parasitic, anti-microbial, hepatoprotective, anti-HIV, anti-diabetic, and many others that will be mentioned in this article. This manuscript will provide future direction, action mechanisms, applications, and the recent collective information of medicinal mushrooms. In addition to many unknown metabolites and patented active metabolites are also included.
Mushrooms degrade matter to produce metabolite for sustaining life. For degradation they produce enzymes and certain metabolites. Both the enzymes and the metabolites are of use for human. The metabolites have medicinal applications. The traditional use and the scientific work on some traditionally used medicinal mushrooms have been discussed here. Some of the mushrooms are Auricularia delicata, A. polytricha, A. auricular, Agaricus blazei, Coprinus comatus, Cordyceps spp., Fomes fomentarius, Fomitopsis pinicola, Ganoderma lucidum, etc. Auricularia delicata has been used in the traditional medicine of Manipur, India, for dysentery and liver healing therapy. A scientific investigation done by one of the authors on traditionally used Auricularia species showed its hepatoprotective activity. The compound isolated from the ethyl acetate extract was chlorogenic acid. It is known to have hepatoprotective activity. This has been a good example illustrating that traditional medicine is a good lead to drug discovery.
Medicinal mushrooms have tremendous potential in production of bioactive compounds with diverse bioactivities while the biochemical potential of some specific mushroom strains (autochthonous for the region) in production of specific bioactive agents may be of the main importance in a continuous search for novel strains with supreme activities all over the world.
In this study, the ethanolic (EtOH) and water (H2O) extracts of wild‐growing polypore mushroom species were investigated: Trametes versicolor (L.) Lloyd and Stereum subtomentosum Pouzar. This study was designed to determine total phenol (TP), flavonoid (TF) and protein content (TPR) as well as LC/MS/MS phenolic profile related to in vitro antioxidant, antiproliferative (MTT assay) (AP) and DNA fragmentation properties.
The H2O extracts expressed better antioxidant scavenging potential than EtOH showing the highest activity for the T. versicolor (IC50=5.6 μg/mL, IC50=0.6 μg/mL for DPPH. and OH., respectively) while O2.− activity achieved the best activity for S. subtomentosum (IC50=4.1 μg/mL). In contrary, the highest AP activity was obtained for the EtOH extracts of S. subtomentosum (IC50=141.1 μg/mL). The EtOH extracts of both species showed the highest TP, TF and TPR content. Obtained results of DNA degradation indicate genotoxicity potential of the extracts at high concentration. The LC/MS/MS detection showed that the majority of analyzed extracts contained phenolic acids, p‐hydroxybenzoic and protocatechuic acid.
The obtained results suggest that analyzed medicinal mushroom species, T. versicolor and S. subtomentosum, could be of potential interest as new sources of strong natural antioxidants as well as antiproliferative agents in the future.
Analgesia with opioids such as morphine is an effective clinical strategy for the treatment of cancer pain and chronic inflammatory pain. However, long-term use of morphine can cause morphine tolerance (MT), which limits the clinical application of opioids. Polysaccharopeptide from Trametes versicolor (TPSP) is a biologically active macromolecule that exerts anti-tumor, immune-enhancing and pain-relieving effects. In order to address the clinical problem of MT, herein, we investigated the inhibitory effect and mechanism of TPSP in rats with inflammatory pain-morphine tolerance. A chronic inflammatory osteoarthritis pain-morphine tolerance model was simulated by injection of complete Freund's adjuvant (CFA) through the ankle joint cavity and continuous intrathecal administration of morphine. Different doses of TPSP (50 μg/kg, 100 μg/kg and 200 μg/kg) were intrathecally administered for consecutive 3 weeks. Our results indicate that TPSP can significantly inhibit the development of morphine dependence and acute withdrawal in rats, alleviate the decrease of paw withdrawal mechanical threshold and heat stimulation retraction latency. In addition, mechanistically at the molecular level, these effects are elicited via up-regulation of the cannabinoid type 2 receptor, up-regulating the level of β-endorphin, and reducing the levels of IL-1, NO and PGE2. In summary, we report for the first time the application of TPSP as an adjunctive therapy strategy for the relief of MT in clinic.
Approximately 130 medicinal functions are thought to be produced by medicinal mushrooms and fungi, including: antitumor, immunomodulating, antioxidant, radical scavenging, cardiovascular, anti-hypercholesterolemia, antiviral, antibacterial, anti-parasitic, antifungal, detoxification, hepato-protective, anti-diabetic, and other effects. Many, if not all, higher Basidiomycetes mushrooms contain biologically active compounds in fruit bodies, cultured mycelium, and cultured broth. Special attention is paid to mushroom polysaccharides. The data on mushroom polysaccharides and different secondary metabolites are summarized for approximately 700 species of higher Hetero- and Homobasidiomycetes. Numerous bioactive polysaccharides or polysaccharide-protein complexes described from medicinal mushrooms appear to enhance innate and cell-mediated immune responses, and exhibit antitumor activities in animals and humans. Whilst the mechanism of their antitumor actions is still not completely understood, stimulation and modulation of key host immune responses by these mushroom compounds appear central. Particularly, and most importantly for modern medicine, are polysaccharides and low-molecular-weight secondary metabolites with antitumor and immunostimulating properties. Approximately 400 studies have been conducted worldwide with numerous published clinical trials on medicinal mushrooms. Several of the mushroom compounds have proceeded through Phase I, II, and III clinical studies, and are used extensively and successfully in Asia to treat various cancers and other diseases. Special attention is stressed to many highly important unsolved problems in the study of medicinal mushrooms.
This review highlights some of the most promising information on five common medicinal mushrooms that are being used in clinical practice throughout the world. Although medicinal mushrooms have been used since ancient times, only recently has western medicine begun to look at research to support its use. Immunomodulating and antitumor effects of mushrooms appear to hold potential benefits through their polysaccharides, either in the form of beta glucans or protein complexes. This article will review the current literature focusing on the evidence supporting the clinical efficacy of mushrooms and their extracted derivatives and the purported mechanisms by which they modulate the human body.
Edible fungi have been consumed as medicines and food in Asian countries since time immemorial. Health benefits of edible fungi are mainly associated to polysaccharides, which are major bioactive components. Contemporary phytochemical and pharmacological studies have proved that polysaccharides are one of the major active ingredients in different types of edible and medicinal fungi. It has been demonstrated that polysaccharides exhibit significant biological activities, including immunomodulation, antitumor, antioxidant, anticancer, and antiviral activities. The purpose of the present review was to summarize previous and current references regarding structural characterization and biological activities of different fungal polysaccharides.
OBJECTIVE: To elucidate the chemical structure of polysaccharide CUP from fungus Coriolus unicolor, and compare with the polysaccharides from Coriolus versicolor in the aspects of compoments and structure. METHODS: GC analysis, infrared spectrum, periodate oxidation, methylation and NMR were used to determine the structure of CUP. RESULTS: CUP was composed of glucose. Its molecular weight was about 1.3 × 104. The main linkage form in CUP was β-(1→3). But some α-(1→3), β-(1→6), α-(1→4), (1→3,6) and (1→4,6) linkages also existed in the molecules. CONCLUSION: CUP is similar with the polysaccharides from Coriolus versicolor in monosaccharide composition and chemical structure, but it is different in molecular weight and protein content.
Mycelial characteristics of dikaryotic collections of 6 medicinal polypore mushrooms (Fomes fomentarius, Fomitopsis pinicola, Ganoderma adspersum, G. applanatum, G. lucidum, and G. resinaceum) with different geographical origins (Armenia, China, France, Iran, Italy, and Russia) were screened. A total of 42 polypore collections were molecularly identified by sequencing the internal transcribed spacer region of the ribosomal RNA genes' cluster, and a phylogenetic tree was constructed. Morphological characteristics of 37 cultures were observed on agar media (malt extract agar, potato dextrose agar) at different temperatures (25, 30, 35, and 38°C) at a pH of 6.0. Colony morphology, pigmentation of mycelium and agar, mycelial growth rate, in vitro teleomorph formation, and other macromorphological characteristics were thoroughly described and illustrated. Micromorphological features of mycelia, such as different hyphal structures, clamp cells, presence and type of asexual sporulation, chlamydospores, and others were observed. The taxonomic significance of the mycelial characteristics revealed was estimated. The obtained results will assist further biotechnological cultivation of medicinal polypore mushrooms to develop novel health care biotechnological products.
The Trametes (=Coriolus) versicolor polysaccharide (CVP) is well known as an antitumor drug in clinical applications. Although recent studies have demonstrated that CVPs can inhibit the proliferation of cancer cells in vitro and in vivo, different purity levels of CVPs have a different affect on various cancer cells. In this study, crude CVPs were extracted and purified from T. versicolor dry fruit bodies by hot-water extraction, ethanol precipitation, and phenol-vitriolic colorimetry. The in vitro cytotoxic activities of CVPs were examined on the human hepatoma cancer (QGY) cell lines by using an MTT assay. The cell cycle and cell death (apoptosis) of QGY cells were investigated by flow cytometry. The expression of genes involved in the apoptosis process, such as p53, Bcl-2, and Fas, was also studied using reverse transcriptase-polymerase chain reaction (RT-PCR) techniques. These results showed that CVPs inhibited the proliferation of QGY in low concentrations (<20 mg/L) and the IC 50 value was 4.25 mg/L. Changes that are characteristic of apoptosis, such as a found trapezoidal belt with DNA, were observed in the QGY cells treated with CVPs. There was a significant decrease in the expression of the cell cycle-related genes (p53, Bcl-2, and Fas) in these cells following treatment with CVPs. These results thus indicate that CVPs can be a potential candidate to ameliorate toxic effects when used in cancer therapy.
The main target of the present review is to draw attention to the current perspectives, advances, evidences, challenges, and future development of medicinal mushroom science in the 21st century. Medicinal mushrooms and fungi are thought to possess approximately 130 medicinal functions, including antitumor, immunomodulating, antioxidant, radical scavenging, cardiovascular, anti-hypercholesterolemic, antiviral, antibacterial, anti-parasitic, antifungal, detoxification, hepatoprotective, and antidiabetic effects. Many, if not all, higher Basidiomycetes mushrooms contain biologically active compounds in fruit bodies, cultured mycelium, and cultured broth. Special attention is paid to mushroom polysaccharides. The data on mushroom polysaccharides and different secondary metabolites are summarized for approximately 700 species of higher hetero- and homobasidiomycetes. Numerous bioactive polysaccharides or polysaccharide-protein complexes from the medicinal mushrooms described appear to enhance innate and cell-mediated immune responses, and exhibit antitumor activities in animals and humans. Whilst the mechanism of their antitumor actions is still not completely understood, stimulation and modulation of key host immune responses by these mushroom compounds appear central. Polysaccharides and low-molecular-weight secondary metabolites are particularly important due to their antitumor and immunostimulating properties. Several of the mushroom compounds have been subjected to Phase I, II, and III clinical trials, and are used extensively and successfully in Asia to treat various cancers and other diseases. Special attention is given to many important unsolved problems in the study of medicinal mushrooms.
The relationship between mushrooms and man can be traced far back into antiquity. More recently, certain mushrooms (medicinal mushrooms) have been shown to be a valuable source of bioactive compounds with potent and unique medicinal properties. Mushroom-derived polysaccharides can modulate animal and human immune responses and inhibit certain tumour growths. Several of these compounds are now used extensively and successfully in Asia as complimentary and mainstream therapies to treat various cancers in combination with chemo and radiotherapy.
Approximately 14,000 described species of the 1.5 million fungi estimated in the world produce fruiting bodies that are large enough to be considered as mushrooms. The world market for the mushroom industry in 2005 was valued at over $45 billion. The mushroom industry can be divided into three main categories: edible mushrooms, medicinal mushroom products, and wild mushrooms. International bodies/forums have developed for each of these segments of the mushroom industry that have helped to bring them to the forefront of international attention: (1) International Society of Mushroom Science, for edible mushrooms; (2) World Society for Mushroom Biology and Mushroom Products, for mushroom biology and medicinal mushroom products; and (3) International Workshop on Edible Mycorrhizal Mushrooms, for some wild mushrooms. The three international bodies/forums have done much to promote each of their respective fields, not the least of which is bringing together scientists in international forums for useful discussions, encouraging research, and the dissemination of valuable information. The outlook for many of the known mushroom species is bright. Production of mushrooms worldwide has been steadily increasing, mainly due to contributions from developing countries such as China, India, and Vietnam. There is also increasing experimentally based evidence to support centuries of observations regarding the nutritional and medicinal benefits of mushrooms. The value of mushrooms has recently been promoted to tremendous levels with medicinal mushrooms trials conducted for HIV/AIDS patients in Africa, generating encouraging results. However, harvests of highly prized edible mycorrhiza mushrooms are continuously decreasing. This has triggered research into devising methods for improved cultivation. It is hoped that there will be even more research into this area, so that larger quantities can be massively harvested through semicultivation methods. Technological developments in the mushroom industry in general have witnessed increasing production capacities, innovations in cultivation technologies, improvements to final mushroom goods, and utilization of mushrooms' natural qualities for environmental benefits. However, there is always the need to maintain current trends and to continue to seek out new opportunities. The challenge is to recognize opportunities such as increasing consumption capabilities with the increase in world population and to take advantage of this by promoting the consumption of mushrooms.
The present review analyzes the history, current status, and future trends in the study of medicinal mushrooms. The target of the present review is to draw attention to many critically important unsolved problems in the future development of medicinal mushroom science in the 21st century. Special attention is paid to mushroom polysaccharides. Many, if not all, higher Basidiomycetes mushrooms contain biologically active polysaccharides in fruit bodies, cultured mycelium, and cultured broth. The data on mushroom polysaccharides are summarized for approximately 700 species of higher Hetero- and Homobasidiomycetes. The chemical structure of polysaccharides and its connection to antitumor activity, including possible ways of chemical modi fication, experimental testing, and clinical use of antitumor or immunostimulating polysaccharides, as well as possible mechanisms of their biological action, are discussed. Particularly, and most importantly for modern medicine, are polysaccharides with antitumor and immunostimulating properties. Several of the mushroom polysaccharide compounds have proceeded through Phase I, II, and III clinical trials and are used extensively and successfully in Asia to treat various cancers and other diseases. A total of 126 medicinal functions are thought to be produced by medicinal mushrooms and fungi, including antitumor, immunomodulating, antioxidant, radical scavenging, cardiovascular, antihypercholesterolemia, antiviral, antibacterial, antiparasitic, antifungal, detoxification, hepatoprotective, and antidiabetic effects.
Fungal Diversity, 55 (1), 1-35 (2012).
Medicinal mushrooms have been valued as natural sources of bioactive compounds since times immemorial and have been recognized as potential immunomodulating and anti-cancer agents. Their consumption has consistently been shown to have beneficial effects on human health. Cancer is a generic term for several types of diseases that can be chronic and are responsible for a large number of deaths worldwide. Although there has been considerable progress in modern cancer therapy research, difficulties in understanding the molecular behavior of various types of cancers and the numerous side effects experienced by patients from treatments means that this whole subject area is still problematic. Thus, biological immunotherapy using natural bioactive compounds as supportive treatments in conventional cancer therapies has become in vogue. Bioactive metabolites isolated from medicinal mushrooms have shown potential successes in cancer treatment as biological immunotherapeutic agents that stimulate the immune system against cancer cells. They also act as an effective source of anti-cancer agents, capable of interfering with cellular signal transduction pathways linked to cancer development and progression. In this review we compile available data on the characteristics of medicinal mushrooms that appear to be particularly effective as biological immunotherapeutic agents. Major consideration is given to biological constituents and the putative mechanisms of action by which bioactive compounds act on the human body. Consideration is also given to the benefits that have been claimed for the use of mushrooms in treating cancer and the future prospects of using medicinal mushrooms as potent supportive candidate bioagents for treatment of cancers is discussed.
Fungal Diversity, 56 (1), 1-29 (2012).
Diabetes mellitus is a life-threatening chronic metabolic disease caused by lack of insulin and/or insulin dysfunction, characterized by high levels of glucose in the blood (hyperglycemia). Millions worldwide suffer from diabetes and its complications. Significantly, it has been
recognized that type 2 diabetes is an important preventable disease and can be avoided or delayed by lifestyle intervention. Presently, there are many chemical and biochemical hypoglycemic agents (synthetic drugs), that are used in treating diabetes and are effective in controlling hyperglycemia. However, as they may have harmful side-effects and fail to significantly alter the course of diabetic complications, natural anti-diabetic drugs from medicinal plants have
attracted a great deal of attention. Medicinal mushrooms have been valued as a traditional source of natural bioactive compounds over many centuries and have been targeted as potential hypoglycemic and anti-diabetic agents. Bioactive metabolites including polysaccharides, proteins, dietary fibres, and many other biomolecules isolated from medicinal mushrooms and their cultured mycelia have been shown
to be successful in diabetes treatment as biological antihyperglycemic
agents. In this review we discuss the biological nature of diabetes and, in particular, explore some promising mushrooms that have experimental anti-diabetic properties, preventing or reducing the development of diabetes mellitus. The importance of medicinal mushrooms as agents of medical nutrition therapy and how their metabolites can be used as supportive candidates for prevention and
control of diabetes is explored. Future prospects for this field of study and the difficulties and constraints that might affect the development of rational drug products from medicinal mushrooms are discussed.
Coriolus versicolor (CV) is a medicinal mushroom widely prescribed for the prophylaxis and treatment of cancer and infection in China. In recent years, it has been extensively demonstrated both preclinically and clinically that aqueous extracts obtained from CV display a wide array of biological activities, including stimulatory effects on different immune cells and inhibition of cancer growth. The growing popularity of aqueous CV extracts as an adjunct medical modality to conventional cancer therapies has generated substantial commercial interest in developing these extracts into consistent and efficacious oral proprietary products. While very limited information is available on the physical, chemical, and pharmacodynamic properties of the active principles present in these extracts, there has been sufficient scientific evidence to support the feasibility of developing at least some of these constituents into an evidence-based immunodulatory agent. In this article, the background, traditional usage, pharmacological activities, clinical effects, adverse reactions, active constituents, and regulatory aspects of CVare reviewed. Presented also in this review are the current uses and administration, potential drug interactions, and contraindication of aqueous extracts prepared from CV
A total of 103 patients with advanced gastric carcinoma were randomized after curative surgery to receive an alternate administration of carbazilquinone (CQ and PSK (Krestin) or carbazilquinone alone. Each course of therapies started 1 week after the surgical operation and therapy schedules consisted of 9 courses. In each course of 6 weeks, CQ (2 mg/m2/week) was administered on day 0, 8, and 15. In combined immunochemotherapy group, PSK was given orally in 3-divided doses of 2 g/m2/day from the day of the third CQ administration for consecutive 4 weeks. Estimated survival rate and cumulative survival curve were compared utilizing the data up to 7 years after the operation. There was no overall significant difference in survival rates between the CQ plus PSK group and the CQ alone group, but a group of patients whose disease was classified as S1 + S2(N1–2) survived significantly longer when treated with the combination of CQ and PSK. Neither in more advanced cases (> S3 or > N3) nor in cancers of early stages, the addition of PSK provided an additive effect. The favorable result obtained in one subgroup treated with PSK, suggests that the use of this agent in treating gastric cancers should be carefully evaluated in terms of serosal infiltration and nodal metastasis.
A controlled study using adjuvant PSK immunotherapy in patients with nasopharyngeal carcinoma was initiated with the aim of improving survival by enhancing the host immune system against tumour cells. A total of 38 patients were randomly selected, all of whom had previously received radiotherapy with or without chemotherapy. Eight patients in the PSK immunotherapy group (n = 21) developed local recurrence, three of whom later died due to distant metastasis. In the control group (n = 17) three patients developed local recurrence while six patients developed distant metastasis. All of these six patients later died due to disease progression. It seems that PSK exerts its antitumour effect systemically; the risk of distant metastasis occurring is decreased, but it is apparently ineffective in improving local disease control. The estimated median survival time of the PSK-treated group compared with the control was significantly increased (35 months versus 25 months, P = 0.043). The 5-year survival rate was also significantly better in the PSK immunotherapy group (28% versus 15%, P = 0.043). It is concluded that PSK deserves careful consideration as an important immunotherapeutic agent in the management of nasopharyngeal carcinoma.
2nd edition of the first book on the topic published in North America. The first edition was self-published in October, 1986.
An exploration of tradition, healing, and culture. Covers the history of the uses of fungi for healing, including nutritional value, summary of cultural uses, history, and science on over 100 species. Shamanistic uses of hallucinogenic fungi.
Botanica Press Imprint, published by The Book Publishing Co., Summertown, TN. 251 pp. with illustrations.
To investigate the molecular mechanism of polysaccharide krestin (PSK) on atherosclerosis's prevention and treatment. Macrophages were cultured and treated with or without PSK initially, Macrophage apoptosis was induced by NO and oxidized low-density lipoprotein (ox-LDL), Expression of inducible nitric oxide synthase (iNOS) mRNA by Raw264.7 macrophages as assessed by RT-PCR. PSK can inhibit ox-LDL-induced macrophage apoptosis and promote NO-induced macrophages apoptosis; Raw264.7 macrophages can be induced to express iNOS mRNA when stimulated with PSK, IFN-γ and LPS in vitro, PSK can enhance the effects of IFN-γ and LPS, suppress the inhibition effects of ox-LDL. The prevention and treatment effects of PSK on atherosclerosis may be realized by inducing iNOS.
Objective: To study the analgesic effect of polysaccharide peptide (PSP) isolated from Coriolus versicolor on acute and chronic inflammatory pain. Method: The analgesic effect of PSP was investigated with three inflammatory pain models including liquor formaldehyde test, carrageenan-induced inflammation and adjuvant-induced arthritis in Wistar rats. Results: A significant dose-dependent analgesic effect of PSP was observed both on acute (liquor formaldehyde and carrageenan-induced inflammation) and chronic (adjuvant-induced arthritis) inflammatory pain. The analgesic effect of PSP lasted about two hours. As compared with pethidine, the analgesia induced by PSP was weaker in intensity and shorter in duration. Conclusion: The polysaccharide peptide has a significant analgesic effect on acute and chronic inflammatory pain.
Sixty-six different species of higher fungi (72 different collections) were coded and evaluated for pharmacologic activity using the hippocratic screening procedure in rats. Twenty-two species exhibited no significant activity and were considered inactive. Four species were considered neither inactive nor active (no apparent dose-response activity since symptoms were detected only at the highest dosage administered). Of the remaining species, three had definite parasympathomimetic activity, eight had psychotropic activity, five contained metabolic poisons, six had some mild depressant activity on the central nervous system, fourteen had some potency as diuretics, two possessed the ability to relax skeletal muscle, three had some tranquilizing activity, and one species appeared to contain a sympathetic stimulant. These figures include two fungi with apparent dual activity depending on when and where collected: Clitocybe oreades, and Helvella lacunosa.
BACKGROUND: Numerous studies demonstrated that patients with advanced cancer have impaired cell-mediated immunity caused by an imbalance between Th1 and Th2 responses. Recently a dichotomy in monocytes analogous to the Th1 and Th2 cell dichotomy has been proposed. Proinflammatory M1 monocytes express a MHC class II+ B7+ CD16- phenotype. In contrast, anti-inflammatory M2 monocytes express the MHC class II- B7- CD16+ phenotype and mediate ADCC. M1 cells generate IL-12, which facilitates the development of Th1 cells, whereas M2 cells generate IL-10, which facilitates the generation of Th2 cells. The balance of the two types of monocytes is one of the most important factors for regulation of the immune system. METHODS: Peripheral blood samples were collected preoperatively from 27 patients with digestive cancers, and 9 healthy volunteers. The proportions of MHC class II+ monocytes and monocytes producing intracellular cytokines (IL-10, MCP-1 and IL-12) were determined with flow cytometry. In 10 patients with colorectal cancers, these analyses were performed before and after oral administration of PSK (three g/dayx7 days). The proportions of CD16+ neutrophils producing intracellular cytokines (IL-10, MCP-1 and IL-12) were analysed simultaneously. RESULTS: The percentages of MHC class II+ monocytes decreased as the cancer progressed. The percentages of monocytes producing IL-10 and MCP-1 were significantly higher in the far-advanced cancer group than in the healthy group (p<0.01). The proportions of monocyte producing IL-10 and MCP-1 in the patients with colorectal cancers decreased significantly after PSK administration (p<0.05). No significant difference was noted between the groups in the percentages of neutrophils producing intracellular cytokines. CONCLUSION: Cancer patients tend to develop an M2-dominant status. Such monocyte evaluations could find applications in the diagnosis and therapeutic monitoring of cancer patients. PSK can apparently counteract the M2-dominant condition in patients with digestive cancers and may improve the balance between Th1 and Th2.
Based on the results of randomized controlled trials against malignant tumors, protein-bound polysaccharide (PSK) was approved in Japan for treatment of resected cases of gastric cancer, curatively resected cases of colorectal cancer, and for palliation of small, cell lung cancer, on the condition that PSK was administered in combination with chemotherapeutic agents. Various mechanisms in the anti-tumor activity of PSK on the molecular and genetic levels have been elucidated to a considerable extent. Even though the evidence for the usefulness of PSK in cancer biotherapy is thought to be sufficient, however, the greater part of medical and surgical oncologists still do not have confidence in it. To overcome this difficulty, it is necessary not only to determine the criteria for selecting responders to PSK, but also to decide its optimal dosage. Essentially, PSK should be administered in combination with chemotherapeutic agents, which are able to modulate or preserve host immune response in cancer patients. In the near future, hopefully, PSK will be a useful immunopotentiator in postoperative adjuvant biotherapy against gastroenterological cancer, promoting the immune surveillance system that can eradicate relatively small tumor burdens such as from micrometastases remaining after curative resection. In addition, by potentiating the basic immune activity of a cancer-bearing host, PSK could augment the therapeutic effect of specific immunotherapies, such as tumor vaccine therapy, immuno-cell therapy, and gene therapy.
The antitumor effect of extracts obtained from Agaricus blazei was compared with that of extracts obtained from Coriolus, PSK. BALB/c mice received simultaneous intradermal injections of Meth-A tumor cells in both the right primary tumor (2 × 106 cells) and left metastatic tumor (2 × 105 cells), and were then injected with 5 mg of extracts in the right tumor on days 3, 4 and 5 (double grafted tumor system). PSK induced cure of not only the primary solid tumor but also the metastatic, distant tumor. Agaricus extracts induced regression of the primary tumor and inhibition of growth of the metastatic tumor. The tumor cells on day 7 from extract-treated primary tumors and from metastatic tumors were cultured for 24 hours and their culture supernatants were assayed for macrophage chemotactic activity (MCF). Significant MCF activity was detected in PSK-treated primary and metastatic tumor tissue and in Agaricus extract-treated metastatic tumor tissue. Immunosuppressive acidic protein (IAP) was found to be produced by activated macrophages. IAP in serum was increased transiently soon after intradermal injection of both extracts. The physicochemical analysis showed that both extracts were protein (17-30%)-bound glucan. These results indicate that Agaricus preparation has a direct cytotoxic effect on primary tumor and PSK induced a sequential antitumor immune mechanism on primary and metastatic tumors.
PSK (Krestin), a protein-bound polysaccharide, is known to be an immunomodulating agent. In addition, PSK was reported to have an anti-angiogenic effect in vivo, but the mechanism was unknown. In this study, we investigated the mechanism by which PSK affects angiogenesis. PSK inhibited the proliferation of human umbilical vein endothelial cells (HUVECs) in the absence of basic fibroblast growth factor (bFGF) but inhibited more effectively in its presence. PSK at a high concentration slightly suppressed tube formation of HUVECs and their adhesion to extracellular matrix proteins. PSK also suppressed the bFGF-dependent MAP kinase phosphorylation. A gel filtration experiment demonstrated direct binding of PSK to 125I-bFGF. PSK (5mg/kg, i. v.) injection reduced the bFGF-induced angiogenesis in an in vivo rat cornea assay. These data suggest that PSK binds to bFGF and interferes with its signal transduction to inhibit the proliferation of HUVECs, resulting in the suppression of angiogenesis.
The fruit bodies of 97 species of wood-rotting fungi, mainly of Polyporaceae and related families, were examined for the distribution of triterpenes and sterols. Triterpene acids of lanostane group were detected exclusively from the fungi causing brown-rot of woods, while sterols were found to occur commonly in both brown-rot and white-rot fungi. The most abundant sterol was found to be ergosta-7,22-dien-3β-ol. The presence and absence of the triterpene acids is discussed from the point of view of fungal phylogeny.
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.
The aim of this report is to evaluate retrospectively the data from a prospective randomized study of 158 esophageal cancer patients who actually completed therapy with protein-bound polysaccharide P (PSK) and the 5-year survivals with and without raised α1-antichymotrypsin and sialic acid levels to determine the value of these parameters in predicting effectiveness of immunotherapy.
There was a significant difference in survival between the patients with and without PSK therapy. The survival of the radiochemotherapy plus PSK group treated for >3 months was significantly better than that of the radiochemotherapy group. Among the patients with abnormal levels of α1-antichymotrypsin and sialic acid, those who received PSK may have a significantly better survival than those without PSK.
These results indicate that the preoperative serum levels of α1-antichymotrypsin and sialic acid may possibly predict the effectiveness of immunotherapy using PSK.
The crude extracts of the European wood-rotting fungus Polyporus versicolor contain cytotoxic principles. Two of these have been isolated by monitoring the purification by tests on hepatoma cells grown in vitro. They are polyoxygenated derivatives of ergosterol, characterized by the partial structure Δ7, 9α-OH.
We examined the effectiveness of postoperative adjuvant chemotherapy with mitomycin C (MMC), 1-(2-tetrahydrofuryl)-5-fluorouracil (tegafur), plus PSK, an immunomodulator, for patients with advanced gastric cancer who underwent histological curative resection. The effect of chemotherapy on prognostic serosal (ps) invasion [ps(−) or ps(+)] and lymph node metastasis [n(−) or n(+)] was examined. One hundred eighteen patients were in the no-chemotherapy group and 137 were on the drugs. The median follow-up time for the 86 survivors at the time of analysis was 13.8 years. With regard to prognostic factors, there were no differences between the two groups. Generalized Wilcoxon test of the two survival patterns revealed a P value of .0351, and the survival rate for 15 years was 45.7% for patients in the no-chemotherapy group and 56.9% for those of the chemotherapy group. In particular, adjuvant chemotherapy was effective for patients with ps(−)n(+) (P <.05) and ps(+)n(−) ( P <.05), but not for those with ps(−)n(−) and ps(+)n(+).
Our findings show that the concomitant prescription of MMC, tegafur, and PSK improves the 15-year survival rate for patients with advanced gastric cancer, following curative resection. As the survival rate is low for the patients with ps(+)n(+), an even more aggressive postoperative chemotherapy is recommended.
Transforming growth factor β1 (TGF-β1) and matrix metalloproteinases (MMPs) produced by tumor cells play important roles in
tumor invasion. PSK, a protein-bound polysaccharide, is widely used in Japan as an immunopotentiating biological response
modifier for cancer patients. In this study, we focused on the effects of PSK on invasiveness, TGF-β1 production, and MMPs
expression in two human tumor cell lines, pancreatic cancer cell line (NOR-P1) and gastric cancer cell line (MK-1P3). PSK
significantly decreased the invasiveness of both cell lines through Matrigel-coated filters but did not affect cell viability,
proliferation, or adhesion. Decreased invasion was associated with the inhibition of TGF-β1, MMP-2, and MMP-9 at both mRNA
and protein levels as assessed by reverse transcriptase-polymerase chain reaction, gelatin zymography, and enzyme-linked immunosorbent
assay. Antibody against TGF-β1 neutralized the MMP activities of both cell lines. PSK also suppressed the expression of urokinase
plasminogen activator (uPA) and uPA receptor but did not change plasminogen activator inhibitor-1 (PAI-1) expression. Western
blot analysis showed that PSK reduced uPA protein expression but not PAI-1 expression in the both cell lines. These results
indicate that PSK suppresses tumor cell invasiveness through down-regulation of several invasion-related factors including
TGF-β1, uPA, MMP-2, and MMP-9.
A randomized, controlled trial of adjuvant immunochemotherapy with PSK
(Kureha Chemical Industry Co., Tokyo, Japan) in curatively resected colorectal cancer was studied in 35 institutions in the Kanagawa prefecture. From March 1985 to February 1987, 462 patients were registered. Four hundred forty-eight of those patients (97.0 percent) satisfied the eligibility criteria. The control group received mitomycin C intravenously on the day of and the day after surgery, followed by oral 5-fluorouracil (5-FU) administration for over six months. The PSK
group received PSK
orally for over three years, in addition to mitomycin C and 5-FU as in the control group. At the end of February 1990, the median follow-up time for this study was four years (range, three to five years). The disease-free survival curve and the survival curve of the PSK
group were better than those of the control group, and differences between the two groups were statistically significant (disease-free survival,P
=0.013; survival,P
=0.013). These results indicate that adjuvant immunochemotherapy with PSK
was beneficial for curatively resected colorectal cancer.
We investigated the action of a protein-bound polysaccharide, PSK, on transforming growth factor-β (TGF-β). (1) In in vitro-mixed culture of peripheral blood mononuclear cells (PBMC) from healthy human and mitomycin C-treated human colon cancer cells, PSK or polyclonal antibody to TGF-β significantly enhanced incorporation of -thymidine into PBMC, and apparently decreased TGF-β1 levels of acid-treated culture supernatant. (2) PSK or the antibody interfered with the quantitation by enzyme immunoassay of TGF-β1 in acid-treated supernatant of the mixed culture. (3) PSK was suggested to form a complex with -human recombinant TGF-β1 standard, when changes in molecular weight of radioactivities were assessed by gel filtration. Recombinant human TGF-β1 inhibited growth of mink lung epithelial cell line Mv1Lu and promoted collagen synthesis in rat kidney fibroblast cell line NRK49F, but the complex did not have such activities. (4) In addition to TGF-β1, PSK bound with TGF-β2 and platelet-derived growth factor; however, PSK did not bind with 22 other species of cytokines and growth factors. (5) Protein moiety of PSK is suggested to play an important role in the expression of the activity. These results suggest that PSK modulates the biological activity of TGF-β1 by binding to its active form.
Long-term adjuvant immunochemotherapy carried out on the gastrectomized patients with stomach cancer was reported. The protocol comprises the administration of large-dose of Mitomycin-C (20+10) mg just after gastrectomy and the long-term administration of PSK, FT-207 or (PSK+FT-207). Almost no side effects were observed. According to the studies on the immunological parameters, the increased reactions in PPD skin test and lymphocyte blastogenesis induced by PHA and PWM were observed remarkably in group (P+F) 3 or 6 months after gastrectomy. As for the survival rate, group (P+F) showed the most preferable results at one year in stage IV, at two years in stage III and at three years in all the stages, respectively after gastrectomy.
A prospective clinical trial was undertaken in 121 patients with stomach cancer to compare immunochemotherapy with 5-fluorouracil and FT-207 combined with OK-432 or PS-K, immunostimulators, and plain chemotherapy with 5-fluororacil and FT-207. Of the 121 patients who received immunochemotherapy, 67 patients (group A) had undergone curative removal of the tumor. The other 54 patients had undergone noncurative tumor removal or had recurrence after non-curative tumor removal and they were divided into two groups (groups B and C) on the basis of lymphocyte reactivity induced with PHA. Although group A exhibited a significant increase in PHA-induced lymphocyte transformation and a trifling increase in lymphocyte counts, its survival rate within a 36 month period did not differ from that of the peer controls. Group B, composed of 21 patients showing improvement of PHA-induced lymphocyte transformation, significantly prolonged its survival compared to the peer controls. The survival of group C, composed of 33 patients showing a gradual drop in PHA-induced lymphocyte transformation, was not prolonged compared to the peer control patients; and they showed significant decreases in lymphocyte counts. The overall survival of group B and group C was not superior to that of the 48 peer controls.
A postoperative long term chemotherapy was carried out against stage IV gastric cancer with Mitomycin-C, Futraful and a plant polysaccharide, PS-K. The 2-year survival rate was 15 per cent in patients who received an intraoperative Mitomycin-C alone, while it increased to 34 per cent in those receiving the anticancer agents for a prolonged period. The postoperative long term chemotherapy is assumed to be an effective means of improving the therapeutical results of gastric cancer.
A new small polypeptide was isolated from the crude extraction of polysaccharide peptide of Coriolus versicolor (Cov-1) by HPLC and CIEF. It has a smaller molecular weight (10K) compared with that of PSP (100K) and was named small peptide of Coriolus versicolor, SPCV. It was found that SPCV possesses potent cytotoxic effect on human tumor cell lines of HL-60, LS174-T, SMMU-7721, and SCG-7901. The IC50 of SPCV on HL-60 was 30 micrograms/ml. The inhibition rates of leukemia cells and SCG-7901 were significantly higher in SPCV treated group than that in PSP and PSK groups. SPCV also has immunopotentiating effect as it increased WBC and IgG levels. Pretreatment of SPCV for two weeks decreased the incidence of tumor mass in nude mice inoculated with tumor cells.
The prognostic value of immunosuppressive acidic protein (IAP), which is known to suppress various immune responses in cancer patients, was studied in a prospective randomized trial of advanced gastric cancer patients, designed to evaluate the effect of PSK, a kind of biological response modifier with protein-bound polysaccharides. Preoperative serum IAP levels were determined in 228 patients who received radical gastric resection and tests conducted in one laboratory by the single radial immunodiffusion (SRID) method. All patients were followed up for 24 months or more. There was an overall significant difference in disease-free survival time in favour of the PSK-treated group compared with the control group. Preoperative IAP values were strongly associated with disease-free survival time. The statistical analysis to define an appropriate cut-off level for IAP was performed using Cox's proportional hazards model. The most significant difference was observed at the threshold value of 580 micrograms/ml, the hazard ratio being 2.13 with a 95% confidence interval [1.17, 3.88] (P = 0.013). Patients in the PSK-treated group with a preoperative IAP of lower than 580 micrograms/ml showed improved disease-free survival (P = 0.029), however, no significant difference was seen between the two groups when the preoperative IAP exceeded the threshold level. From these results, 580 micrograms/ml is postulated to be the most appropriate threshold value for predicting the prognosis of advanced gastric cancer patients, and it is suggested that PSK would be most effective in patients whose preoperative IAP level is lower than the threshold level.
The present study was designed to assess the effects of the protein-bound polysaccharide PSK on the immunological status of patients with gastrointestinal cancer. Twenty-nine gastric and 18 colorectal cancer patients were randomly assigned to either the control or PSK group. Patients in the PSK group were given 3.0 g of PSK orally before surgery, either daily or every other day. Patients in the control group received no PSK. The data of peripheral blood lymphocytes (PBL) were compared before and after administration of PSK, and those of the regional node lymphocytes (RNL) were compared between the control and the PSK group. The results indicate that the effects of PSK were significantly influenced by the duration of administration, but not by the frequency of administration. In the patients belonging to the short term PSK group (administration <14 days), the response of the PBL to PSK and Con A become significantly stronger compared to before the administration of PSK, whereas the cytotoxicity against K562 and KATO-3, and the proportion of CD16+ cells increased significantly in those patients belonging to the long term PSK group (≧14 days). In addition, the proportion of CD9 + 11b + suppressor T cells decreased in the RNL of the short term PSK group, whereas the proportion of CD4 + Leu8 - helper T cells in the RNL increased in the long term PSK group.
These results suggest that the oral administration of PSK leads to the suppression of suppressor cells in the RNL. Thus, increased numbers of cytotoxic effector cells appear to be activated in the PBL while helper T cells predominate in the RNL.
A protein-bound polysaccharides (PSP) isolated from Coriolus versicolor in Shanghai, at the concentrations of 100-800 micrograms/ml promoted lymphocyte proliferation. PSP 25 mg/kg ip into mice for 5 d antagonized the inhibition of IL-2 production by cyclophosphamide from activated T lymphocytes and restored the suppressed T-cell-mediated delayed, type hypersensitivity response to normal. PSP 10-1000 micrograms/ml induced interferon alpha and gamma production from human peripheral leukocytes 4 and 8 times respectively higher than that of the control groups. Moreover, PSP also increased phagocytic functions of host reticulo-endothelial system. The results suggest that the anti-tumor effects of PSP may be related to its potentiation of host immunological responses.
A cooperative study on surgical adjuvant immunochemotherapy for prevention of postoperative recurrence of gastric cancer was carried out by Kondo's group from July 1974 to December 1977. A total of 848 patients with gastric cancer underwent curative resection were eligible. Of 848 patients, 819 cases with complete description of patient's background were evaluable: Group A (surgery + MMC + 5-FU:chemotherapy) 253 cases, group B (surgery + MMC + 5-FU + OK-432 or PSK:immunochemotherapy) 282 and group C (surgery alone) 284. The 5-year corrected survival rates of total cases using Cox's proportional hazard model were 76.2% with group A, 73.6% with group B and 73.3% with group C. And the 10-year survival rates were 67.6% with group A, 64.3% with group B and 63.9% with group C. The difference in survival rate among groups A, B and C was not statistically significant. In the evaluation of prognostic factors by Cox's proportional hazard model, level of curative resection, extent of resection, histological stage and Kajitani's classification had an influence upon survival rates, in which degrees of metastasis in lymph node and serous infiltration were also involved. The significance of postoperative adjuvant immunochemotherapy has not been clarified.
To examine the clinical efficacy and the mechanism of action of polysaccharide K (PSK), a protein-bound polysaccharide extracted from a Basidiomycetes fungus, a randomized double-blind trial was performed by administering PSK to 56 patients and a placebo to another group of 55 patients after surgical operations on their colorectal cancers. The rate of patients in remission (or disease-free) was significantly higher in the PSK group than in the placebo group; the difference between both groups was statistically significant at P less than 0.05 by the log-rank test. The survival rate of patients was also significantly (P less than 0.05) higher in the PSK group than in the control group. The most significant laboratory finding was that polymorphonuclear leukocytes from PSK-treated patients showed remarkable enhancement in their activities, such as random and/or chemotactic locomotion, and phagocytic activity, when compared with those in the control group. In conclusion, PSK was useful as a maintenance therapy for patients after their curative surgical operations for colorectal cancer. The beneficial effects were probably due to the activation of leukocyte functions as one of the many biological-response-modifying (activities induced by PSK).
After oral administration of 20 mg/kg of PSK, a significant level of interferon (IFN) activity was detected in the sera of BCG (1 mg/mouse)-sensitized mice. A low titer of IFN was also detected in the sera of all of 4 cancer patients after 3 g/day oral administration of PSK for 7 consecutive days. Intratumoral administration of PSK (5 mg/mouse) strongly inhibited the growth of Meth-A solid tumors in male BALB/c mice and led to complete regression of tumors and resistance to reinoculated tumors in the host animals. Subsequently, the antimetastatic effect of PSK was examined in a "double grafted tumor system" in which mice first received simultaneous intradermal inoculations of Meth-A in the right (10(6) cells) and left (2 X 10(5) cells) flanks and were then injected with PSK in the right tumor on day 3. PSK significantly inhibited the growth of the left, non-treated tumor. When mice received an inoculation of Meth-A (2 X 10(5) cells) in the left flank and PSK was injected subcutaneously in the right flank on day 3 (single tumor system), the growth of the tumor was not inhibited. These findings suggest that intratumoral PSK immunotherapy in one region has an effect on tumor growth in another region.
We found that PSK has an antiviral effect on human immunodeficiency virus (HIV) in vitro. One of the mechanisms of this effect is attributable to the inhibition of binding of HIV with lymphocytes. Here, we found that PSK inhibits reverse transcriptase in a non-competitive way in vitro. Such inhibition may be important in its anti-HIV effect as well as its inhibitory effect on the binding of HIV with lymphocytes.
The ability of various known anti-HIV antivirals to inhibit four different strains of human immunodeficiency virus type 1 (HIV-1), a strain of type 2 (HIV-2), and a human T-cell lymphotropic virus type I (HTLV-I) was tested. The tested substances included two sulfated polysaccharides (lentinan sulfate and dextran sulfate) and a nonsulfated polysaccharide PSK, E-P-LEM, glycyrrhizin sulfate, and nucleoside analogues (AZT and DHT). The effects of the substances were measured quantitatively with two different assays: (i) inhibition of cell-free viral infection and (ii) inhibition of the fusion reaction induced by cell-to-cell infection. The results showed that cell-free infection of HIV-1 and HIV-2 was almost completely blocked in the presence of all of the substances tested. However, cell-to-cell infection by HIV-1, HIV-2, and HTLV-I was inhibited only by the polysaccharides, E-P-LEM, and glycyrrhizin sulfate but not by the two nucleoside analogues. Moreover, the extent of inhibition of the fusion reaction by the substances varied significantly from strain to strain in HIV-1.
The Gastric Cancer Immunochemotherapy Study Group, constituted of 412 institutions, carried out six independent trials simultaneously from 1978 to 1981. A total of 4,456 cases were subjected to the study, from which 826 cases (18.5%) were excluded due to the violence of entry criteria. Curative gastrectomy, followed by a combination of mitomycin C (MMC), Ftorafur (FT)and Krestin (PSK) produced better postoperative survivals than either combination of MMC and FT, or MMC and PSK (5-year survival rate: 71.7% in MMC + FT + PSK, 64.1% in MMC + PSK, and 58.5% in MMC + FT). In the subset of patients with negative nodes (n(-)), and with involved serosa by histological examination (ps(+)), a combination of FT and PSK after gastrectomy seemed to be more favorable for the post-operative survivals than the single use of either drug. Four drug combinations of MMC, FT, PSK and Picibanil (OK-432) also had a clinical benefit in the group of patients with poorly differentiated adenocarcinoma, compared with chemotherapy alone. These results, though there are biases due to excluding 18.5% of cases, suggest some clinical benefits in the control of cancer relapse after surgery. The conclusion should be confirmed by a further elaborate trial.
To evaluate the efficacy of PSK for adjuvant immuno-chemotherapy in patients who had undergone radical gastrectomy, a randomized controlled trial has been in progress in collaboration with 46 institutions in the Chubu district of Japan. A total of 262 patients were registered for this trial during the two years from July 1985 to June 1987 with a centralized registration system, and were allocated into the 5-FU+PSK group (Group P) and 5-FU alone group (Group C) by the minimization method following the random permuted blocks method. Between the two groups, the parameters of sex, age, serosal invasion (S), lymph-node metastasis (N), and the combination of S . N factor levels were distributed without significant differences. An induction treatment with MMC 6 mg/m2 was given to all patients following curative gastrectomy and on the 7th post-operative day. Two weeks after surgery, Group P received alternately PSK 3 g/day for 4 week and 5-FU 150 mg/day for 4 weeks as one course, and 10 courses were given. Group C received 5-FU alone for 4 weeks using alternate rest interval for 4 weeks. Since both experimental and clinical studies suggested that alternate treatments using PSK and anticancer agents were effective, treatment in this trial alternated PSK and 5-FU. A final follow-up study will be completed in June 1992, when all patients shall have survived more than 5 years after surgery. The administration of 5-FU was completed by January. 1989, but PSK has been administered to group P. The period from 18 to 42 months after surgery was reached in all eligible patients (253) at the end of December 1988. The disease-free survival curves and overall survival curves of group P were significantly (p = 0.018 and p = 0.045,) better than those of group C.
The Japanese consume enormous amounts of drugs on prescription, some of which are not legally available elsewhere in the world. The reason is a defective national system for drug approval and dispensing.
In order to improve the postoperative prognosis of gastric cancer patients we have performed preoperative endoscopic intratumoral administration of various biological response modifiers. In the present study we have investigated the kinetics and the immune response augmenting effect of intratumorally injected PSK, a protein-bound polysaccharide preparation, by immunohistochemical methods using anti-PSK antibody and various other antibodies. PSK-containing cells were located in the tumor tissues and follicular marginal zones of regional lymph nodes. Intratumorally administered PSK appeared to be phagocytized by the histiocytes and to cause them to become antigen-presenting cells. These cells may play a major role in augmenting immune responses in gastric cancer patients.
The mouse macrophage-like cell line, J774.1, spontaneously released differentiation-inducing factor(s). When these cells were treated with a protein-bound polysaccharide, PSK, significantly higher amounts of differentiation-inducing activity were accumulated in the culture supernatant. PSK directly stimulated human myelogenous leukemic cell differentiation induced by J774.1 conditioned medium or by tumor necrosis factor. Among four subfractions of PSK, only the highest molecular weight fraction (MW greater than 200 kD) exerted such a stimulating effect.
PSK, a biological response modifier (BRM), was studied to determine its anti-viral activity on human immunodeficiency virus (HIV) in vitro. Either a novel infection system using human T-cell lymphotropic virus type I (HTLV-I)-carrying MT-4 cells or a coculture system using MOLT-4 cells and its virus-producing cells MOLT-4/HIVHTLV-IIIB which induces multinucleated giant cells very efficiently was used. PSK almost completely blocked the cytopathic effect such as giant cell formation and HIV-specific antigen expression both in MT-4 cells and MOLT-4 cells at a concentration of 0.4 and 0.8 mg/ml, respectively. Pretreatment of the virus with PSK may specifically interfere with early stages of HIV infection by modifying the viral receptor.
Body fluids from cancer patients (sera, pleural effusions and ascites) tended to inhibit phosphofructokinase (ATP: D-fructose-6-phosphate 1-phosphotransferase, EC 2.7.1.11) (PFK), the rate-limiting key enzyme in the glycolysis pathway, when analysed using aqueous ATP solution separately from the main reaction mixture. A protein-bound polysaccharide from Coliolus versicolor QUEL (Krestine, PSK) antagonistically elevated the activity of the enzyme. It was found that PSK stabilized PFK in a similar way to certain enzyme stabilizers such as proteins and polysaccharides. Furthermore, it was clarified that PSK worked as an ion radical scavenger that could capture 1O2, O-2, and OH X radicals released from lipoperoxides. In other words PSK protects PFK from hyperoxidation by lipoperoxides.
The host-mediated antiviral effect of two biological response modifiers (BRM), OK-432 and PS-K, against murine cytomegalovirus (MCMV) was evaluated in normal and immunologically deficient mice of the same litters. In normal littermate mice, BALB/c (nu/+) or C57BL/6 (bg/+), the BRM-induced resistance against MCMV infection was evidenced by increase in fifty percent lethal doses, decrease in titers of viruses replicated in the target organs and augmentation of natural killer (NK) cell activity of the spleen cells. In T cell-deficient, athymic nude mice, BALB/c (nu/nu), the protective effect was manifested by prolongation of the survival, decrease in the virus titers, and increase in the NK-cell activity, but without decrease in mortality. In NK cell-deficient, beige mutant mice, C57BL/6 (bg/bg), the BRM-induced protection was nullified or minimized, and there was little difference in those parameters between BRM-treated and untreated mice. However, with higher doses of OK-432, but not PS-K, or with sublethal doses of MCMV, the NK cell activity was slightly augmented in the beige mutant mice. Thus both NK cell and T cell activity are essential for mice to overcome acute MCMV infection and it is likely that the protective effect of BRM manifests itself fully, at least in immunologically intact mice.
For a period of about three years from September 1980, a randomized controlled study was performed on colo-rectal cancer patients who had undergone an absolute curative operation. After operation and administration of 30 mg of Mitomycin (20 mg on the day and 10 mg on the day following the operation), all patients were randomly divided into two groups which received the treatments as follows; Group A, 750 mg x 2/day of FT-207 suppositories, was administered for one year from the 2 nd week after operation; Group B was given FT-207 3.0 g/day of PSK orally for one year. Group A included 71 patients, of whom 46 had colon cancer and 25 had rectal cancer. Group B included 53 patients, of whom 30 patients had colon cancer and 23 had rectal cancer. There was no difference between the two groups in terms of patients' background factors. In regard to the 5-year survival rates of these patients by means of the Kaplan-Meier Method, Group A and B showed 80.8% and 91.4%, respectively, but no significant difference was observed. In the colon cancer patients, 5-year survival rates were 88.6% and 93.0% in Group A and B, and in the rectal cancer patients, they were 68.0% and 87.5% in Group A and B, respectively. The survival rate of Group B was always slightly higher than that of Group B in all analyses, in which we considered such factors as degree of progression, depth of cancer invasion of the wall, lymphnode metastases and vascular invasion. There were no differences between both groups in the patterns and times of recognition of the recurrences, but the number of cases evidencing recurrences within 2 years tended to be smaller in Group B. Thus, it was suggested that PSK was effective for prolongation of the survival period in colo-rectal cancer patients after absolute curative operation.