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Maitake MD-Fraction aid cancer patients?
Abstract
Maitake mushroom (Grifola frondosa) MD-fraction containing beta-1,6 glucan with beta-1,3 branched chains has previously exhibited strong anticancer activity by increasing immune-competent cell activity.1,2 In this non-random case series, a combination of MD-fraction and whole maitake powder was investigated to determine its effectiveness for 22- to 57-year-old cancer patients in stages II-IV. Cancer regression or significant symptom improvement was observed in 58.3 percent of liver cancer patients, 68.8 percent of breast cancer patients, and 62.5 percent of lung cancer patients. The trial found a less than 10-20 percent improvement for leukemia, stomach cancer, and brain cancer patients. Furthermore, when maitake was taken in addition to chemotherapy, immune-competent cell activities were enhanced 1.2-1.4 times, compared with chemotherapy alone. Animal studies have supported the use of maitake MD-fraction for cancer.
... Deficiency of vitamin A is a serious public health problem affecting most of the countries especially pregnant women and children of low income countries such as South-East Asia and Africa (Fig 12). [69][70][71][72][73][74][75][76][77][78][79][80][81][82][83][84] In year 2000 a variety of rice was genetically modified for beta carotene (vitamin A precursor) synthesis and iron proficiency. This vitamin A and iron proficient rice named "Golden Rice" was developed by Peter Beyer, Ingo Potrykus, Peter Burkhardt, and Xudong Ye in association with the company Syngenta. ...
... The D-and MD-fractions have been shown to have outstanding anti-tumor activity and have consequently been proposed for phase I/II clinical trials in the United States and Japan. The anti-tumor activity of D-Fraction in mice lies on the balance between T lymphocyte subsets Th-1 and Th-2 and potentiated the activation of helper T-cells, resulting by increasing cellular immunity and workers have suggested its useful immunotherapeutic agent for cancer patients (71). For the innate and adaptive immune responses, activated macrophages are responsible for the production of cytokines, interleukin-1 beta (IL-1β), tumor necrosis factor-alpha (TNF-), nitric oxide (NO), and other inflammatory mediators (72). ...
... Deficiency of vitamin A is a serious public health problem affecting most of the countries especially pregnant women and children of low income countries such as South-East Asia and Africa (Fig 12). Journal of Huazhong Agricultural University, 33 (2014) [69][70][71][72][73][74][75][76][77][78][79][80][81][82][83][84] In year 2000 a variety of rice was genetically modified for beta carotene (vitamin A precursor) synthesis and iron proficiency. This vitamin A and iron proficient rice named "golden rice" was developed by Peter Beyer, Ingo Potrykus, Peter Burkhardt, and Xudong Ye in association with the company Syngenta. ...
... The D-and MD-fractions have been shown to have outstanding anti-tumor activity and have consequently been proposed for phase I/II clinical trials in the United States and Japan. The anti-tumor activity of D-Fraction in mice lies on the balance between T lymphocyte subsets Th-1 and Th-2 and potentiated the activation of helper T-cells, resulting by increasing cellular immunity and workers have suggested its useful immunotherapeutic agent for cancer patients (71). For the innate and adaptive immune responses, activated macrophages are responsible for the production of cytokines, interleukin-1 beta (IL-1β), tumor necrosis factor-alpha (TNF-), nitric oxide (NO), and other inflammatory mediators (72). ...
In this study we have analysed the data set over dengue disease having different symptoms for India and abroad. We have collected the data for the years 1988-2009 using World Health Organization (WHO) report 2011 and have determined correlations among different symptoms for dengue and chikungunya disease; and also between the affected rate and mortality rate for dengue disease in India. However, we have also constructed a parabolic curve over affected and death rates of India and nations throughout the sea region (shown in Fig.-1) using least square method with the help of computer C programming. Finally, graphical illustrations have been made to interpret the trends study of the intensity of the proposed dengue disease.
... Deficiency of vitamin A is a serious public health problem affecting most of the countries especially pregnant women and children of low income countries such as South-East Asia and Africa (Fig 12). Journal of Huazhong Agricultural University, 33 (2014) [69][70][71][72][73][74][75][76][77][78][79][80][81][82][83][84] In year 2000 a variety of rice was genetically modified for beta carotene (vitamin A precursor) synthesis and iron proficiency. This vitamin A and iron proficient rice named "golden rice" was developed by Peter Beyer, Ingo Potrykus, Peter Burkhardt, and Xudong Ye in association with the company Syngenta. ...
... The D-and MD-fractions have been shown to have outstanding anti-tumor activity and have consequently been proposed for phase I/II clinical trials in the United States and Japan. The anti-tumor activity of D-Fraction in mice lies on the balance between T lymphocyte subsets Th-1 and Th-2 and potentiated the activation of helper T-cells, resulting by increasing cellular immunity and workers have suggested its useful immunotherapeutic agent for cancer patients (71). For the innate and adaptive immune responses, activated macrophages are responsible for the production of cytokines, interleukin-1 beta (IL-1β), tumor necrosis factor-alpha (TNF-), nitric oxide (NO), and other inflammatory mediators (72). ...
This edited book comprises of twenty four articles written by several authors. All articles are multidisciplinary in nature relating to diversified aspects of biotechnology, ecology etc including history of biotechnology, biotechnology in agriculture, biotechnological interventions in other areas, present and future scenarios in biotechnology, biotechnology in cancer research, biotechnology in waste management etc. The most noteworthy feature is that the book's last chapter has been coauthored by the world's master microbiologist and biotechnologist Prof Ananda M. Chakrabary of Illinois State University, USA, popularly known as Mr Pseudomonas, creator of the first GMO of the world.
... A glycoprotein (PCP-3A), purified from Pleurotus citrinopileatus, showed antitumor activity [108]. Kodama et al. [109] isolated a low molecular weight protein fraction from Grifola frondosa, which showed antitumor activity. ...
... Several terpenes isolated from G. lucidum showed anti-inflammatory activity. Some triterpenes from G. lucidum (ganoderic acid C and derivatives) are able to inhibit the biosynthesis of cholesterol [109], while other triterpenes (ganoderic acid F) contribute to atherosclerosis protection [134]. The antioxidative and free radical effects of triterpenoids from G. lucidum have also been shown [38]. ...
... A glycoprotein (PCP-3A), purified from Pleurotus citrinopileatus, showed antitumor activity [108]. Kodama et al. [109] isolated a low molecular weight protein fraction from Grifola frondosa, which showed antitumor activity. ...
... Several terpenes isolated from G. lucidum showed anti-inflammatory activity. Some triterpenes from G. lucidum (ganoderic acid C and derivatives) are able to inhibit the biosynthesis of cholesterol [109], while other triterpenes (ganoderic acid F) contribute to atherosclerosis protection [134]. The antioxidative and free radical effects of triterpenoids from G. lucidum have also been shown [38]. ...
... Maitake-derived polysaccharide-based drugs were subjected to clinical trials. The Japan group reported cancer regression in about 58.3% of liver cancer patients, 68.8% of breast cancer patients, and 62.5% of lung cancer patients [421]. At the same time, there was only a 10-20% improvement for leukemia, stomach cancer, and brain cancer patients. ...
Traditional herbal medicine (THM) is a “core” from which modern medicine has evolved over time. Besides this, one third of people worldwide have no access to modern medicine and rely only on traditional medicine. To date, drugs of plant origin, or their derivates (paclitaxel, vinblastine, vincristine, vinorelbine, etoposide, camptothecin, topotecan, irinotecan, and omacetaxine), are very important in the therapy of malignancies and they are included in most chemotherapeutic regimes. To date, 391,000 plant and 14,000 mushroom species exist. Their medical and biochemical capabilities have not been studied in detail. In this review, we systematized the information about plants and mushrooms, as well as their active compounds with antitumor properties. Plants and mushrooms are divided based on the regions where they are used in ethnomedicine to treat malignancies. The majority of their active compounds with antineoplastic properties and mechanisms of action are described. Furthermore, on the basis of the available information, we divided them into two priority groups for research and for their potential of use in antitumor therapy. As there are many prerequisites and some examples how THM helps and strengthens modern medicine, finally, we discuss the positive points of THM and the management required to transform and integrate THM into the modern medicine practice.
... Lentinan, a β-D-glucan isolated from the mushroom Lentinula edodes was found to have synergistic effect with paclitaxel in prolonging patients survival in gastric cancer and to treat non-small cell lung cancer (Zhang et al., 2018). Mao et al. (2019) reported synergism of Grifola frondosa polysaccharides with 5-Fluorouracil on Heps-tumor mice, while Kodama et al. (2002) provided evidence for the combination of a glucan-enriched MD-fraction and whole Maitake (G. frondosa) powder on cancer regression and symptom improvement in breast cancer patients. ...
Mushroom β-d-glucans have demonstrated immunomodulatory activity, which is initiated by their recognition by specific receptors on immune system cells surfaces. Studies indicated that β-d-glucans may present a synergistic effect with chemotherapy drugs. In this study, a linear β-(1 → 6)-d-glucan (B16), isolated from A. bisporus and previously characterized (Mw: 8.26 × 10⁴ g/mol), was evaluated about its capacity to modulate THP-1 macrophages towards an M1 phenotype and induce an antitumoral activity. This was evidenced by the production of pro-inflammatory markers upon B16 treatment (30; 100 μg/mL). The breast tumor cells (MDA-MB-231) viability was not affected by treatment with B16, however, their viability markedly decreased upon treatment with the drug doxorubicin. The results showed a synergic effect of B16 and doxorubicin, which reduced the viability of MDA-MB-231 cells by 31%. Furthermore, B16 treatment provided a sustainable M1 state environment and contributed to diminish the resistance of breast cancer cells to the doxorubicin treatment.
... Agaricus and Pleurotus Gameiro et al. (2013); Kang et al. (2012)2.To upgrade the immune power, they have been used as medicine. They also respond against the cancerKodama et al. (2002);Gao et al. (2003) Maehara et al. (2012 ...
Environmental pollution with synthetic organic compounds has become a hazardous issue
world-wide. Thus, efforts are greatly required for bioremediation of soil pollutants and for the present
scenario of excessive use of harmful chemicals. A rapid cost effective and ecologically responsible method of
clean-up is “bioremediation” which utilizes micro-organisms to degrade toxic pollutants is an efficient
economical approach. It has been exposed newly that the mycelia of edible mushroom will hit a great
performance within the reclamation of defective surroundings (myco-restoration) through myco-filtration
(using mycelia to filter water or mycelia area unit used as a filter to get rid of cyanogenic materials and
microorganisms from water within the soil), myco-forestry, mycoremediation, and myco-pesticides. As we all
know that mushroom forming fungi, are amongst nature's most powerful decomposers, secreting strong extra
cellular enzymes due to their aggressive growth and biomass production, that’s why the present review article
basically emphasizes on the use of fungal mycelia in bioremediation (myco-remediation) and studies on the
uses of mushrooms for bioremediation.
... In particular, in the treatment of patients affected by astrocytoma, pain was reduced and various side effects such as appetite loss, vomiting, nausea, hair loss, and leukopenia were ameliorated. 15 The anticancer action and immune system influence of polysaccharides extracted from Ganoderma lucidum (Curtis) P. Karst. (GL-PS) was demonstrated in glioma-bearing rats, in which GL-PS inhibited glioma growth and increased rat survival. ...
Medicinal mushrooms are considered an unlimited source of polysaccharides (mainly β-glucans) and polysaccharide-protein complexes and possess various immunological and anticancer properties. In addition, their use in integrative medicine leads to a clear reduction of side effects in patients undergoing chemotherapy or radiotherapy. The literature reports a number of beneficial effects of using mushrooms as health supplements in patients affected by high-grade glioma. The effects of medicinal mushrooms on side effects in patients with brain cancer and a case study report are also described in this review.
... Maitake's effectiveness in fighting tumors was also highlighted in another study, in which patients with stage II-IV cancers were given mushroom powder or MD-fraction [72]. In high percentages of breast cancer patients (68.8%), lung cancer patients (62.5%), and liver cancer patients (58.3%), a cancer regression or a significant symptom improvement were observed, and the stimulation of immune-competent cell activities when the mushroom treatment was given alongside chemotherapy. ...
Medicinal mushrooms have important health benefits and exhibit a broad spectrum of pharmacological activities, including antiallergic, antibacterial, antifungal, anti-inflammatory, antioxidative, antiviral, cytotoxic, immunomodulating, antidepressive, antihyperlipidemic, antidiabetic, digestive, hepatoprotective, neuroprotective, nephroprotective, osteoprotective, and hypotensive activities. The growing interest in mycotherapy requires a strong commitment from the scientific community to expand clinical trials and to propose supplements of safe origin and genetic purity. Bioactive compounds of selected medicinal mushrooms and their effects and mechanisms in in vitro and in vivo clinical studies are reported in this review. Besides, we analyzed the therapeutic use and pharmacological activities of mushrooms.
... Due to the toxicity and side effects of the chemotherapeutic drugs, more and more cancer patients have turned to herbal medicine for complementary treatment. The MD-fraction from G. frondosa, the lentinan agent from L. edodes and PSK and PSP from T. versicolor are in clinical use for adjuvant tumor therapy (immunotherapy), in addition to the major cancer therapies like chemotherapy, radiotherapy and surgical operation [1,52] and in HIV patients [53]. Thus, the MD-fraction is known to reduce tumor cell viability and was found to be the most potent compound, enhancing the immune system, via oral administration or injection, leading to the highest reduction of the rate of cancer proliferation. ...
Mushrooms are widely used in Asian medicine, both as dietary supplements and as nutraceutical foods. Some principal fungi have recently become popular in Europe for their nutritional and health benefits, and a large number of bioactive compounds have been isolated in several taxa showing antioxidant, anti-inflammatory, antiviral, antitumor activities and other biological properties with great therapeutic application. Separate research has been done separately for the different species. The aim of the present review was to give an overview of the present knowledge regarding bioactive compounds in ten of the most common species, their options in therapeutic use and, for the first time, their possible toxicity or adverse effects. Boletus edulis, Ganoderma lucidum, Grifola frondosa, Hericium erinaceus, Hypsizygus marmoreus, Lentinula edodes, Morchella esculenta, Pleurotus ostreatus, Poria cocos and Trametes versicol have great potential as functional foods and as a source of drugs for pharmaceutical science and medicine. Some adverse effects, however, were found to occur in individual daily consumption and during clinical trials. More research is needed to make a good rational use of these medicinal compounds.
... Our search yielded a total of 272 studies from the electronic databases. After sorting out repetitive hits, irrelevant and several single arm studies with various outcomes, e.g., dose escalation studies (Kodama et al., 2002;Gao et al., 2003b;Yoshimura et al., 2010;Palomares et al., 2011;Torkelson et al., 2012;Ohno et al., 2013;Suzuki et al., 2013;Twardowski et al., 2015) as well as many publications on in vitro and animal models, nine studies met our inclusion and exclusion criteria for a narrative review on medicinal mushrooms in human cancer therapy (eight RCTs, one CCT) ( Table 1). A large variety of cancer entities, studied sample sizes, outcomes, treatment durations and observation times were seen ( Table 1). ...
Medicinal mushrooms are widely used in East Asia for the treatment of various diseases, especially in complementary cancer care. While there is a growing interest in medicinal mushrooms in Western countries and an increasing number of pre-clinical studies indicate distinct anti-cancer and regenerative properties, little is known about their potential relevance for clinical practice. This review aims to provide an overview of the clinical evidence, significance and potential role of medicinal mushrooms in complementary cancer care. Scientific databases for (randomized) controlled clinical trials evaluating whole spectrum formulations of medicinal mushrooms (mushroom powder and mushroom extracts) in cancer patients during and/or after conventional oncological treatment were searched. Eight studies met our inclusion criteria (eight randomized controlled trials, one controlled clinical trial). The medicinal mushrooms investigated were Agaricus sylvaticus (two trials), Agaricus blazei murill (two trials), Antrodia cinnamomea (one trial), Coriolus versicolor (one trial) and Ganoderma lucidum (three trials); all were compared to placebo and administered orally. A variety of cancer entities, outcomes and treatment durations were observed. Study results suggested beneficial effects of medicinal mushrooms, particularly quality of life and reduction of adverse effects of conventional therapies. Also, positive effects on antitumor activity and immunomodulation were reported, e.g., an increased activity of natural killer cells. In addition, results might suggest a longer survival of cancer patients receiving mushroom preparations, although in most studies this was not significant when compared to placebo. Adverse events of treatment with medicinal mushrooms were poorly reported; gastrointestinal reactions and a decrease in platelet cell count occurred in some cases. The methodological quality of most studies was generally unsatisfying and most results were insufficiently reported in several respects. Medicinal mushrooms may have a therapeutic potential for cancer patients during and after conventional oncological care with regards to quality of life, reduction of adverse effects of conventional care and possibly other surrogate parameters like immune function. There is an urgent need to investigate the safety and possible interactions of medicinal mushrooms. High-quality clinical research is warranted in order to clarify the potential of medicinal mushrooms in cancer therapy.
... It was concluded that G. lucidum could be administered as an adjunct to conventional treatment in consideration of its potential of enhancing tumor response and stimulating host immunity (Jin et al. 2016). An increase in immunological parameters, improvement in life quality, and in single cases prolongation of survival time could be demonstrated also after treatment with A. brasiliensis (Ahn et al. 2004;Talcott et al. 2007) and G. frondosa (Kodama et al. 2002;Konno 2009;Rajamahanty et al. 2009). It should be noted that several mushrooms appear to increase the effects of chemotherapy (Guggenheim et al. 2014). ...
Historical data and current research in Italy reveal the permanent interest of people and scientists toward the importance of fungi as functional food and medicine. This chapter reports the main studies on medicinal mushrooms carried out by Italian researchers on the antibacterial activity, the characterization of β-glucans content, antitumor activity, Alzheimer’s disease, characterization of bioactive compounds, antimicrobial activity, dietary supplementation, chemical contents, and animal health. Currently, in vitro experiments are prevalent with respect to clinical trials on human and animals.
... The findings of clinical trials involving the regular consumption of A. brasiliensis Wasser (syn. A. blazei Murrill sensu Heinemann) (Ahn et al. 2004;Talcott et al. 2007;Motoi et al. 2015) and G. frondosa (Kodama et al. 2002;Konno 2009;Rajamahanty et al. 2009) by healthy volunteers showed improved immunity and, in S. M. Badalyan et al. sylvie.rapior@umontpellier.fr single cases, increased rate of survival and general quality of live (QoL). However, a randomized, double-blind, placebo-controlled trial showed that the extract of A. blazei had no stimulating effect on IL-6, IFN-γ, or TNF-α levels in elderly females (Lima et al. 2011). ...
Fungi are considered one of the most diverse, ecologically significant, and economically important organisms on Earth. The edible and medicinal mushrooms have long been known by humans and were used by ancient civilizations not only as valuable food but also as medicines. Mushrooms are producers of high- and low-molecular-weight bioactive compounds (alkaloids, lectins, lipids, peptidoglycans, phenolics, polyketides, polysaccharides, proteins, polysaccharide-protein/peptides, ribosomal and non-ribosomal peptides, steroids, terpenoids, etc.) possessing more than 130 different therapeutic effects (analgesic, antibacterial, antifungal, anti-inflammatory, antioxidant, antiplatelet, antiviral, cytotoxic, hepatoprotective, hypocholesterolemic, hypoglycemic, hypotensive, immunomodulatory, immunosuppressive, mitogenic/regenerative, etc.). The early record of Materia Medica shows evidence of using mushrooms for treatment of different diseases. Mushrooms were widely used in the traditional medicine of many countries around the world and became great resources for modern clinical and pharmacological research. However, the medicinal and biotechnological potential of mushrooms has not been fully investigated. This review discusses recent advances in research on the pharmacological potential of mushrooms and perspectives for their clinical application. _____Key-words:
Bioactive compounds · Clinical application · Ethno-mycopharmacology · Medicinal mushrooms · Pharmacological potential.
... Certain species of medicinal mushrooms produce bioactive compounds with antitumor activity that could work as adjuvants together with cancer chemotherapy. Indeed, polysaccharide-rich extracts from Grifola frondosa and Trametes versicolor species have already shown to play relevant clinical benefits in cancer patients [21,22]. Recent evidence suggested a direct antitumor effect of polysaccharides-extracts in cancer cells independently of its action on the immune system. ...
Colorectal cancer (CRC) is one of leading causes of mortality in western countries and novel treatment strategies are required. The medicinal application of mushrooms has been used in traditional medicine in many oriental countries. Polysaccharide-rich extracts obtained from certain medicinal mushroom species have shown antitumor effects in different experimental models. In the present study, we have developed polysaccharide-rich extracts from Trametes versicolor (TV) and Grifola frondosa (GF) fruit bodies. We aim to evaluate the anticancer effects of these polysaccharide-rich extracts in LoVo and HT-29 human colon cancer cells. The in vitro effects were determined by cytotoxicity assay, proliferation assay, wound healing assay and invasion assay. Moreover, the effect on anchorage independent-cell growth was also determined. Our results showed that TV and GF extracts did inhibit human colon cell proliferation and induce cytotoxicity. Furthermore, both fungal extracts significantly inhibited oncogenic potential, cell migration and invasion in colon cancer cells. In addition, extracts induce a more epithelial phenotype, observed by phase contrast images, together with an increase expression of the E-cadherin epithelial marker, detected by western-blotting analyses. Moreover, by using gelatin zymography assays, it was detected a decrease of MMP-2 enzyme activity, a crucial metalloproteinase important for the degradation of the extracellular matrix. Finally, the combination of the extracts with one the most clinical used agents for colorectal cancer, 5-fluorouracil, increases cell cytotoxicity. Taken together our results underscore a potential antitumor effect of polysaccharide-rich extracts obtained from TV and GF in human colon cancer cells lines. These finding may contribute to the reported health effects of fungal extracts.
... Treatment with beta-(1 → 3)-d-glucan resulted in an increased rate of tumor inhibition in a dose-dependent manner, and significantly potentiated immune responses in mice [59]. In another study, Maitake D-Fraction extracted from Grifola frondosa (Maitake mushroom) decreased the size of lung, liver, and breast tumors in > 60% of patients when it was combined with chemotherapy in a two-arm controlled study compared with chemotherapy alone [60]. In a prospective clinical trial of the short-term immune effects of oral beta-glucan in patients with advanced breast cancer, 23 female patients with advanced breast cancer were compared with a control group of 16 healthy females [61]. ...
Purpose
Beta-glucans are biologically active polysaccharides having antioxidant, immunomodulatory, and antiinflammatory properties. This study investigated the transcriptomic profile in peripheral blood of rats with LPS-induced enteritis, which were fed a diet supplemented with high- (G1) and low- (G2) molecular-weight oat beta-glucans.
Methods
Two-color rat gene expression microarrays were applied and the analysis was performed using a common reference design to provide easy means of comparing samples from various experimental conditions against one another. Common reference sample was labeled with cyanine 3 (Cy3) and investigated samples from each experimental group: C-G0 (control group fed semi-synthetic diet), LPS-G0 (LPS-challenged group fed semi-synthetic diet), LPS-G1 (LPS-challenged group fed G1 beta-glucan enriched diet), and LPS-G2 (LPS-challenged group fed G2 beta-glucan enriched diet) were labeled with cyanine 5 (Cy5). Each microarray was performed in quadruplicate. Statistical analysis was performed using one-way ANOVA and Tukey’s HSD post-hoc test (p < 0.05). A multiple testing correction was performed using Benjamini and Hochberg False Discovery Rate < 5%. A quantitative real-time RT-PCR was performed to verify the expression of chosen transcripts.
Results
The microarray analyses revealed differentially expressed transcripts between: the LPS-G0 and the control groups: C-G0 (138 genes), the LPS-G1 and LPS-G0 groups (533 genes), and the LPS-G2 and LPS-G0 groups (97 genes). Several differentially expressed genes in the beta-glucan-supplemented groups encoded proteins belonging to TLR and NLR signaling pathways, as well as prostaglandin synthesis and regulation pathways. Both beta-glucans up-regulated the expression of Atg10, which belongs to the family of autophagy-related genes, suggesting a possible link between autophagy induction and beta-glucan supplementation.
Conclusion
The changes in gene expression observed in the peripheral blood indicate that oat beta-glucans exerted a protective effect in rats with an induced inflammatory state caused by LPS challenge. The greater number of differentially expressed genes was observed in group supplemented with G1 beta-glucan, pointing at the differences in the mode of action of high- and low-molecular-weight beta-glucans in the organism.
... More research is needed before use of medicinal mushrooms can be recommended during breast cancer treatment. [21][22][23][24] ...
A majority of women undergoing conventional treatment for breast cancer also undertake complementary and integrative approaches. Practitioners knowledgeable about the evidence base behind common integrative approaches can help patients attain improved quality of life, and at times, improved survival. Evidence-based recommendations include the following: a plant-based diet for general health after diagnosis, and carbohydrate restriction for patients with estrogen receptor-positive postmenopausal breast cancer may be prudent. Other dietary recommendations include a 13-h daily overnight fast. Carefully selected patients may choose to fast the day before and the day of chemotherapy to decrease side effects. Specific food recommendations include avoidance or limitation of alcohol, and liberal culinary use of cruciferous vegetables, coffee, green tea, soy, and flaxseed. Promising supplements include diindolylmethane and melatonin. Omega 3 fatty acids may help with bone density in patients on aromatase inhibitors, but may increase chemotherapy resistance. Findings regarding the usefulness of multivitamins, vitamin D, vitamin C, and vitamin E are weak and/or mixed different exercise modalities may have different effects and thus play different roles in breast cancer therapy. Aerobic and resistance training combined during breast cancer chemotherapy may confer a survival benefit, while yoga may improve outcome in lymphedema patients. Current evidence suggests that meditation, yoga, breathing, music therapy, guided imagery, and hypnosis may improve mood and quality of life during breast cancer treatment. Acupuncture is useful for treating side effects of breast cancer therapies, including hot flushes, aromatase inhibitor-induced joint pain, chemotherapy-induced peripheral neuropathy, and vulvodynia. Vaginal moisturizers and vaginal rings supplying low-dose estrogen can be useful in the treatment of symptoms of estrogen-deprivation states caused by breast cancer treatments; such symptoms include vaginal dryness, dyspareunia, and sexual dysfunction. Carbon dioxide laser technology can rejuvenate atrophied vaginal mucosa and relieve dyspareunia, allowing avoidance of estrogen therapy. Tertiary sexual health centers are available for referral.
... The β-glucan doesn't have any direct effects on the cancer calls, the effects may be due to the interaction between the gut microbiota and β-glucan, which results in active metabolites which can increase the immune response and results in the apoptosis [77]. Another study on maitake D-fraction was found to reduce the effects of lung, liver and breast tumors and the effects was efficient along with the chemotherapy [78]. The patients with lung cancer were treated with ganoderma polysaccharides for 12 weeks resulted in the altered cytokines levels [79]. ...
... G. frondosa, also known as Maitake, is a culinary as well as medicinal mushroom native to China, North America, and northeastern part of Japan but cultivated worldwide in several countries because of its useful efects [81]. The mushroom is progressively being perceived as a powerful wellspring of polysaccharide with sensational well-being and advanced potential. ...
... times, compared with chemotherapy alone. Animal studies have supported the use of maitake MD-fraction for cancer (38). ...
ß-Glucans are naturally occurring polysaccharides. These glucose polymers are constituents of the cell wall of certain pathogenic bacteria and fungi. The healing and immunostimulating properties of mushrooms have been known for thousands of years in the Eastern countries. These mushrooms contain biologically active polysaccharides that mostly belong to group of ß-glucans. These substances increase host immune defense by activating complement system, enhancing macrophages and natural killer cell function. The induction of cellular responses by mushroom and other ß-glucans is likely to involve their specific interaction with several cell surface receptors, as complement receptor 3 (CR3; CD11b/CD18), lactosylceramide, selected scavenger receptors, and dectin-1 (ßGR). ß-Glucans also show anticarcinogenic activity. They can prevent oncogenesis due to the protective effect against potent genotoxic carcinogens. As immunostimulating agent, which acts through the activation of macrophages and NK cell cytotoxicity, ß-glucan can inhibit tumor growth in promotion stage too. Antiangiogenesis can be one of the pathways through which ß-glucans can reduce tumor proliferation, prevent tumor metastasis. ß-Glucan as adjuvant to cancer chemotherapy and radiotherapy demonstrated the positive role in the restoration of hematopiesis following by bone marrow injury. Immunotherapy using monoclonal antibodies is a novel strategy of cancer treatment. These antibodies activate complement system and opsonize tumor cells with iC3b fragment. In contrast to microorganisms, tumor cells, as well as other host cells, lack ß-glucan as a surface component and cannot trigger complement receptor 3-dependent cellular cytotoxicity and initiate tumor-killing activity. This mechanism could be induced in the presence of ß-glucans.
... In a non-randomized human clinical trial, 36 patients with advanced (stage II-IV) breast, liver, or lung cancer were administered a combination of oral MD-fraction and Maitake tablets. The treatment demonstrated immuneenhancing properties such as increased numbers of IL-2 and CD4+ cells [40]. Furthermore, it was suggested that β-glucans can cooperate with antitumor monoclonal antibodies that are used for cancer immunotherapy [41]. ...
Culinary and medicinal mushrooms are widely used in Asian countries, both as dietary supplements and as nutraceutical foods. They have recently become popular in Europe, as well, for their nutritional and health benefits. In particular, epidemiological studies conducted in Asia suggest that mushroom intake, together with other phytotherapy substances, protects against cancer, specifically gastrointestinal (GI) and breast cancers. Most of the data come from in vitro studies and in vivo experimental animal models. Therefore, in order to translate the updated knowledge to clinical research (i.e., from bench to bedside) a systematic translational research program should be initiated. Future randomized controlled trials comparing the effects of G. frondosa and G. lucidum on conventional treatment outcomes are warranted.
The purpose of this review was to describe the emerging mechanisms of action of the mushrooms’ anticancer functions which makes their use in clinical practice so promising. Clinical effects of mycotherapy (specifically, the use of Ganoderma lucidum and Grifola frondosa) on long-term survival, tumor response, host immune functions, inflammation, and QoL in cancer patients were also addressed. Adverse events associated with mycotherapy were also investigated. Emerging data point to a potential role of G. lucidum for modulating the carcinogenic potential of GI microbiota, which suggests a new complementary and integrated approach to breast cancer treatment.
... In the clinical trials of the anticancer activity of natural β-glucans, schizophyllan was used in combination with the chemotherapy to improve the survival rate in ovarian cancer patients [89]. In addition, maitake D-fraction extracted from Grifola frondosa (Maitake mushroom) was reported to reduce the tumor size mainly lung, liver, and breast tumors in more than 60% of the treated patient [90]. Furthermore, the stimulation of the immune response in lung and colorectal cancer patients treated with ganoderma polysaccharides has been reported upon administration of 5.4 g/day for 12 weeks [91,92]. ...
Natural products with immunomodulatory activity are widely used in treatment of many diseases including autoimmune diseases, inflammatory disorders in addition to cancer. They gained a great interest in the last decades as therapeutic agents since they provide inexpensive and less toxic products than the synthetic chemotherapeutic agents. Immunomodulators are the agents that have the ability to boost or suppress the host defense response that can be used as a prophylaxis as well as in combination with other therapeutic modalities. The anticancer activity of these immunomodulators is due to their anti-inflammatory, antioxidant, and induction of apoptosis, anti-angiogenesis, and anti-metastasis effect. These natural immunomodulators such as genistein, curcumin, and resveratrol can be used as prophylaxis against the initiation of cancer besides the inhibition of tumor growth and proliferation. Whereas, immunostimulants can elicit and activate humoral and cell-mediated immune responses against the tumor that facilitate the recognition and destruction of the already existing tumor. This review represents the recent studies on various natural immunomodulators with antitumor effects. We have focused on the relationship between their anticancer activity and immunomodulatory mechanisms. The mechanisms of action of various immunomodulators such as polyphenolic compounds, flavonoids, organosulfur compounds, capsaicin, vinca alkaloids, bromelain, betulinic acid and zerumbone, the affected cancerous cell lines in addition to the targeted molecules and transcriptional pathways have been review and critically analyzed.
... Fractions of Maitake mushrooms decreased the size of lung, liver and breast cancer when combined with chemotherapy. On the other hand, these effects were less evident in patients with leukemia, stomach and brain cancer which were also treated with Maitake mushroom extracts (Kodama et al., 2002;2003). The D-fraction Maitake combined with the agonist nine of the Toll-like receptor increased the expression of dendritic cell maturation markers and also, increased the interleukin-12 in dendritic cells, but did not increase the production of interleukin-10. ...
A public health issue, Diabetes mellitus, affects millions of people around the globe. Ingestion of foods with a low glycemic index - fiber-rich meals-such as beta-glucans, is increasing as an important alternative for diabetes control. These compounds act reducing parameters such as blood glucose, cholesterol and triglycerides, by decreasing the absorption of glucose and lipids by enterocytes and eventually promote weight loss. Beta-glucans are also described as immunomodulatory agents by stimulating phagocytosis and the production of pro-inflammatory cytokines, increasing host resistance to viral, bacterial, fungal and parasitic infections; or production of anti-inflammatory cytokinesto return homeostasis after an immune response. Besides, some studies are also evidencing anti-tumoral activity. Beta-glucans main effect depends on their origin-yeast, plants or bacteria. Reports of collateral effects and/or toxicity associated with the use of beta-glucans are rare, which contribute to consider this compound for inclusion in a range of therapies. This review aims to evaluate the most different effects of beta-glucans in metabolic and immune systems, discussing its advantages and limitations. © 2017 Viviam de Oliveira Silva, Natalia Oliveira de Moura, Larissa Jahnel Rodrigues de Oliveira, Ana Paula Peconick and Luciano José Pereira.
... It was concluded that G. lucidum could be administered as an adjunct to conventional treatment in consideration of its potential of enhancing tumor response and stimulating host immunity (Jin et al. 2016). An increase in immunological parameters, improvement in life quality, and in single cases prolongation of survival time could be demonstrated also after treatment with A. brasiliensis (Ahn et al. 2004;Talcott et al. 2007) and G. frondosa (Kodama et al. 2002;Konno 2009;Rajamahanty et al. 2009). It should be noted that several mushrooms appear to increase the effects of chemotherapy (Guggenheim et al. 2014). ...
Higher Basidiomycetes and Ascomycetes mushrooms possess various immunological and anticancer properties. They also offer important health benefits and exhibit a broad spectrum of pharmacological activities including antibacterial, antifungal, antiviral, cytotoxic, immunomodulating, anti-inflammatory, antioxidative, antiallergic, antidepressive, antihyperlipidemic, antidiabetic, digestive, hepatoprotective, neuroprotective, nephroprotective, osteoprotective, and hypotensive activities. This minireview summarizes the perspectives, recent advances, and major challenges of medicinal mushrooms with reference to their nutraceutical properties and dietary value, the production of mushroom biomass on various substrates, and the purification, characterization, and pharmaceutical effects of biologically active compounds from medicinal mushrooms.
... A glycoprotein (PCP-3A) was purified from Pleurotus citrinopileatus, which showed antitumor activity (Chen et al. 2009). Kodama et al. (2002) isolated a low molecular weight protein fraction from G. frondosa, which showed antitumor activity. Ngai and Ng (2008) isolated a novel and potent antifungal protein lentin (27.5 kDa) from the fruiting bodies of L. edodes. ...
Mushrooms have been consumed and appreciated worldwide for their exquisite flavor, nutritional value, and medicinal properties. Some of them being nonedible are known only for their medicinal properties. These organisms belong to a taxonomic group of basidiomycetes
or ascomycetes
, which produce multiple potential bioactive compounds such as polysaccharides, proteoglycans, terpenes, phenolic compounds, lectins, peptides, and proteins, among others. These bioactive compounds confer to mushrooms’ antioxidant
, antimicrobial
, antitumor, anti-inflammatory, antineurodegenerative
, antidiabetic, anticancer, antidepressant
, immunomodulating, and others properties. The increasing isolation and purification of new compounds are leading to the discovering of new therapeutical drugs. However, some of the mushrooms of medicinal importance cannot be cultivated and can be only wild-harvested in the specific growing season, which results in a long time and high cost for producing mushroom bioactive compounds. In this sense, it is very important to improve and optimize conditions for mycelial growth in vitro and create new strains by genetic modification in order to produce large amounts of those compounds of interest. These organisms offer an increasing potential in medical applications due to their chemical composition and a wide range of bioactivities. Most of the reports about biologically active compounds
have been focused on in vitro and in vivo (in animal studies) evidence; however, clinical trials need to be carried out.
... A few clinical trials have studied the effect of β-glucans derived from various sources in lung cancer patients (Table 1). Maitake D-Fraction containing β-(1 → 6)-glucan was shown to decrease the size of a lung tumor in >60% of patients when it was combined with chemotherapy in a clinical cohort comparing with chemotherapy alone [88]. Ganoderma polysaccharides are βglucans derived from Ganoderma lucidum (Lingzhi, Reishi) with an antitumor activity which enhance host immune responses in patients with advanced solid tumors. ...
The potential of natural substances with immunotherapeutic properties has long been studied. β-glucans, a cell wall component of certain bacteria and fungi, potentiate the immune system against microbes and toxic substances. Moreover, β-glucans are known to exhibit direct anticancer effects and can suppress cancer proliferation through immunomodulatory pathways. Mortality of lung cancer has been alarmingly increasingly worldwide; therefore, treatment of lung cancer is an urgent necessity. Numerous researchers are now dedicated to using β-glucans as a therapy for lung cancer. In the present attempt, we have reviewed the studies addressing therapeutic effects of β-glucans in primary and metastatic lung cancer published in the time period of 1991–2016.
... Like Shiitake, Maitake is a common food. Conventional toxicology studies are more limited than that found for Shiitake, but include several subchronic (up to 120 days) studies in mice (oral) (Kodama et al., 2002;Nanba, 1997) and a chronic (13 months) study Table 4 Reishi Mycelium -Contribution of mass spectral features that differ from culinary mushrooms to the estimated difference of the raw material from food. in mice (oral) (Nanba, 1997). None of these reported toxicity at any dose. ...
Despite growing popularity in dietary supplements, many medicinal mushrooms have not been evaluated for their safe human consumption using modern techniques. The multifaceted approach described here relies on five key principles to evaluate the safety of non-culinary fungi for human use: (1) identification by sequencing the nuclear ribosomal internal transcribed spacer (ITS1) region (commonly referred to as ITS barcoding), (2) screening an extract of each fungal raw material against a database of known fungal metabolites, (3) comparison of these extracts to those prepared from grocery store-bought culinary mushrooms using UHPLCPDA- ELS-HRMS2, (4) review of the toxicological and chemical literature for each fungus, and (5) evaluation of data establishing presence in-market. This weight-of-evidence approach was used to evaluate seven fungal raw materials and determine safe human use for each. Such an approach may provide an effective alternative to conventional toxicological animal studies (or more efficiently identifies when studies are necessary) for the safety assessment of fungal dietary ingredients.
... and in addition, the side effects of chemotherapy were reduced. The mush- room exerts an antitumour effect primarily by stimulating the immune system through the activation of immune cells and increased production of cytokines -mediators of the immune response (Nanba 1997; Kodama et al. 2002). Maitake polysaccharides have been shown to exert hypoglycaemic effects in patients with type 2 diabetes by reducing their blood sugar levels by over 30% ( Konno et al. 2002). ...
Medicinal mushrooms have been used in traditional medicine and human diet for thousands of years. Nowadays, medicinal mushrooms and their active compounds are being increasingly recognised by conventional medicine, since more and more scientific studies support their therapeutic value. In this book, therapeutic properties and applications of 16 most popular medicinal mushrooms are concisely presented based on scientific research, including clinical trials. In addition, the use of medicinal mushrooms for the treatment of companion, domestic and sport animals is also described.
... The U.S. researchers have been exploring these fascinating organisms for their medicinal properties [5,6]. The βglucan D-fraction of Maitake exerts profound effects on the immune system [7]. It is reported that the Maitake D-Fraction join Dectin-1 receptors present in the outer membrane of macrophages and other white blood cells including natural killer (NK) cells and cytotoxic T (Tc) [8]. ...
The understanding of the molecular mechanisms of the immune tolerance induced by the tumoral microenvironment is fundamental to prevent cancer development or to treat cancer patients using immunotherapy. Actually, there are investigations about "addressed-drugs" against cancer cells without affecting normal cells. It could be ideal to find selective and specific compounds that only recognize and destroy tumor cells without damaging the host normal cells. For thousands of years, mushrooms have been used for medicinal purposes because of their curative properties. D-Fraction, an extract of Maitake (from the edible Grifola frondosa mushroom), rich in β-glucans, exert notable effects in the immune system. Until now, some published articles suggest that Maitake D-Fraction could have anti-tumoral activity, prevent oncogenesis and metastasis in some tumor types. However, there are no clear data about Maitake D-Fraction action on breast cancer prevention and its exact molecular mechanisms are not yet elucidated. The experiments were performed employing 25 female BALBc mice that were treated with and without Maitake D-Fraction Pro4X or Maitake Standard for 15 days by daily intraperitoneal injection. After treatment period, all mice were implanted with murine tumor cells LM3 to induce mammary tumorigenesis. Animals were checked weekly and killed after 46 days of LM3 transplant; percentage of cancer prevention, rate of tumor growing, and overall survival were determined. Under dissection, the internal organs were evaluated histologically and genetically by RT-PCR. We found that 5 mg/kg per day of Maitake D-Fraction Pro4X, administered dairy during 15 days to BALBc mice was able to block more than 60% breast cancer development. However, Maitake Standard prevents oncogenesis in 26% to respect control. In this work, we found that Maitake D-Fraction Pro4X, administered to BALBc mice, prevents breast carcinogenesis, block tumor invasiveness, reduce angiogenesis, and increase overall survival.
Although the living standard and life expectancy have been increasing significantly, we face numerous arising challenges in modern medicine, such as the presence of increasing exogenous triggers of oxidative stress that lead to the emergence of multiple diseases and disorders, the appearance of an increasing number of resistant microorganisms, an immense number of patients suffering from cardiovascular diseases, cancers, diabetes, neurodegenerative disorders as well as autoimmune and rare diseases. Therefore, we need the help of natural sources of active compounds, among which mushrooms are important. They have been an integral part of traditional medicine for centuries, and modern research has confirmed their bioactivities and given them a scientific basis. Numerous species, primarily from the genera Ganoderma, Lentinus, Pleurotus, Innonotus, Trametes, Cordyceps, Agaricus, etc., have shown exceptional immunomodulatory, antioxidative, antihypercholesterolemic, antihypertensive, antitumor, antineurodegenerative, antidiabetic, antimicrobial as well as numerous other potentials. Studies have shown that the mushrooms’ crude extracts, as well as various metabolites, especially polysaccharides, phenolic compounds, terpenoids, and proteins, possess mentioned activities and thereby could be the basis for the development of new, more efficient drugs. However, numerous problems and challenges need to be overcome before mushrooms from the domain of traditional medicine move into the modern one and become part of conventional therapy.KeywordsBioactivitiesDrug developmentFunctional foodMedicinal mushroomsTraditional medicine
This volume of the book “Therapeutic Mushrooms for Diabetes Mellitus: Current Evidences and Future Scope” focuses on the prevalence, causes, management of diabetes mellitus type II. It gives an insight in to the role of mushrooms such as Ganoderma lucidum, Innotus obliquus, Grifola frondosa, Phellinus species, etc. against diabetes mellitus. It highlights the use of mushrom powder, extracts and their bioactive components for the management of diabetic syndrome, various in vitro, in vivo and clinical studies performed to lower hyperglycemia and other diabetes associated secondary abnormalities as well as provides information regarding the mushrooms based antidiabetic market products.The initial part provides information about diabetes mellitus, its causes, treatments available, natural resources for the management of diabetes mellitus, history of use of mushrooms especially against diabetes. The middle part of the book comprises of chapters highlighting 1) the presence of bioctive contituents of antidiabetic mushrooms, 2) the mechanism of action of these antidiabetic mushroom components and 3) in vitro and gestational diabetes mellitus studies performed using antidiabetic mushrooms. The closing portion of the book lays emphasis on 1) in vivo studies and clinical trials done using antidiabetic mushrooms and the avaialble antidiabetic market products of mushrooms.
Agaricus blazei Murrill (AbM) is a medical mushroom which has huge potential commercial value with various health-promoting functions. However, the chemical composition and therapeutic mechanisms of AbM have not been concluded systematically yet. Thus, this study aims to comprehensively summarize the phytochemical profiles and thoroughly characterize the health promotion effects such as the antitumor and antidiabetic impact of AbM in in vivo and in vitro. The AbM consists of abundant bioactive substances; polysaccharides, lipids including ergosterol, sterols, proteins, vitamin B, C and D, and phenolic compounds. Several studies have claimed that Agaricus blazei Murrill polysaccharides (AbMP) had immunoregulation, anti-inflammatory, hepatoprotective, and antitumor function both in vivo and in vitro. Meanwhile, AbM extracts were thought to cure diabetes and bacterial infection, exhibiting anticarcinogenic and antimutagenic functions. But some principles behind health-promoting effects have not been clarified. Additionally, AbM related clinical trials are limited and further discovery need to be conducted. Therefore, this paper has concluded the health promotion impact with corresponding mechanisms of AbM and indicated its potential medical usage as functional food in the future.
Cancer is the leading cause of mortality worldwide and in particular is the fourth most common cause of mortality in women every year. Conventional treatments for cancer are chemotherapy and radiation therapy, which have various kinds of side effects. Hence, there is a high need to develop alternative, efficient, and safer therapies for cancer treatment. β-Glucan, a novel polysaccharide isolated from baker’s yeast Saccharomyces cerevisiae, shows noteworthy cytotoxicity toward a variety of cancer cell lines in vitro. In this research, we characterized the β-glucan with high-performance thin-layer chromatography (HPTLC) analysis and found that d-glucose units with β-1,3 links are the major component of the extracted β-glucan particles. Fourier transform IR (FTIR) analysis confirmed a β-(1→3)-linked glucan structure. In vitro cell cytotoxicity was evaluated by MTT with IC50 136 μg/ml, and therapeutic potential was assessed by various assays using values below and above the IC50. A significant reactive oxygen species (ROS) generation at 50–150 μg/ml of concentrations indicated the apoptosis of cervical cancer cells. Along with ROS generation, these concentrations were also found to induce morphological changes such as fragmentation in DNA upon staining HeLa cells with DAPI. Mitochondrial membrane potential was significantly reduced after increasing the dose of treatment, assessed with the help of MitoTracker dye. Hence, by all these experimental supports, we observed that β-glucan has the potential to slow down the growth of cervical cancer cells, and it can be further investigated for unfolding its complete anticancer potential.
Mushrooms either alone or in combination with conventional cancer treatment have been enhanced the efficacy of chemotherapy and radiotherapy improving the patients' quality of life. These therapy effects have been attributed to polysaccharides; the most potent compounds found in the fungi kingdom. Due to their wide range of biological activity and the backbone of glucose residues linked by β-(1 → 3)-glycosidic bonds, often with attached side-chain glucose residues joined by β-(1 → 6) linkages, the mushroom's polysaccharides, particularly the β-glucans, are the most versatile metabolites. Lentinan, D-fraction, and schizophyllan from Lentinula edodes, Grifola frondosa, and Schizophyllum commune, respectively are well-known β-glucans, however, the precise immunomodulation and anticancer mechanisms of action remain to be uncovered. According to several studies, β-glucan can interact with certain receptors on macrophages and dendritic cells, such as dectin-1 and TLRs, producing different cytokines and, in turn, indirectly activating other immune cells including T and B cells. Moreover, recent findings have proved that β-glucans have a direct cytotoxic effect on cancer cells suppressing proliferation and enhancing apoptosis possibly via multiple pathways such as PI3K/Akt/mTOR, NF-κB-, ERK-, ERα-, caspase- and p53-dependent pathways.
Indeed, this study intends to provide information on the lentinan, D-fraction, and schizophyllan by examining the extraction procedures, chemical composition, and immunostimulatory and antitumoral biological activities. Future research directions should be directed toward improving the validity and reliability of randomized trials to confirm the potential role of β-glucans on the immune system and as anticancer therapy.
This article is a brief, informative work about the health effects of Hen of the Woods (Grifola frondosa).
Fődi A: Gyógyhatású gombák : Az ágas tapló (Grifola frondosa) gyógyhatásáról. In: Magyar Gombász, 2016. vol. 14. (11th official volume) No. 42. pp. 15–16. [Medicinal Mushrooms : Healing properties of Hen of the Woods (Grifola frondosa), in Hungarian]
Magyar Gombász ISSN 1788-4136
The plasticity of the gut microbiota (GM) creates an opportunity to reshape the biological output of gut microbes by manipulating external factors. It is well known that edible fungal polysaccharides (EFPs) can reach the distal intestine and be assimilated to reshape the GM. The GM has unique devices that utilize various EFPs and produce oligosaccharides, which can selectively promote the growth of beneficial bacteria and are fermented into short-chain fatty acids that interact closely with intestinal cells. Here we review EFPs-based interventions for the GM, particularly the key microorganisms, functions, and metabolites. In addition, we discuss the bi-directional causality between GM imbalance and diseases, and the beneficial effects of EFPs on host health via GM. This review can offer a valuable reference for the design of edible fungal polysaccharide- or oligosaccharide-based nutrition interventions or drug development for maintaining human health by targeted regulation of the GM.
Aldolase A (ALDOA) facilitated aerobic glycolysis in cancer cells is a potential target in the treatment of hepatocellular carcinoma (HCC). However, only few effective inhibitors of ALDOA have been reported until now. In this research, we found a polysaccharide called HDPS-4II from Holotrichia diomphalia Bates, which can specifically bind to ALDOA with a dissociation constant of 2.86 µM. HDPS-4II with a molecular weight of 19 kDa was a linear triple-helix glucan composed of ɑ-D-1,4-Glcp and ɑ-D-1,6-Glcp in a ratio of 1.0:10.0. HDPS-4II significantly inhibited aldolase enzyme activity, glycolysis, and further inhibited the expression of phosphorylated AMPKα in HCC cells. Through analyzing ALDOA-overexpressing and -knockdown cells, it was confirmed that ALDOA mediated the viability and glycolysis inhibition of HDPS-4II. Moreover, HDPS-4II administration markedly inhibited tumor growth in mice xenografted with HCCs. These findings suggest that HDPS-4II, as an ALDOA antagonist, is a promising remedy in the treatment and prevention of HCC.
There is significant interest in the use of mushrooms and/or mushroom extracts as dietary supplements based on theories that they enhance immune function and promote health. To some extent, select mushrooms have been shown to have stimulatory action on immune responsiveness, particularly when studied in vitro. However, despite their widespread use for potential health benefits, there is a surprising paucity of epidemiologic and experimental studies that address the biologic activities of mushrooms after oral administration to animals or humans. There have been a number of studies that have addressed the ability of mushrooms to modulate mononuclear cell activation and the phenotypic expression of cytokines and their cognate receptors. There have also been a number of attempts to determine antitumor activities of mushrooms. Such studies are important because many of the components of mushrooms do potentially have significant biologic activity. All data, however, should be tempered by the Possibility that there are toxic levels of metals, including arsenic, lead, cadmium, and mercury as well as the presence of radioactive contamination with ¹³⁷Cs. In this review, we will Present the comparative biology with respect to both immunological and antitumor activities of mushroom extracts and also highlight the need for further evidence-based research.
Mushrooms are macro‐fungi that bear spores enclosed within a fruiting body. They are a well‐known food for humans and have very important nutritional components. They also have great esthetic, culinary, ecological, and commercial importance. Human survival depends upon food, and humans have consumed mushrooms since prehistoric times because edible mushrooms contain an abundance of vitamin B and other several important minerals; they are also low in calories. Several birds and other animals also consume mushrooms, and thus mushrooms are considered an important component of the terrestrial food chain. However, many mushroom species contain toxins and have caused numerous diseases, and death in rare cases.
Microbiological studies have proposed that bacteria are associated with all diseases; hence, the notion of microorganisms facilitating cancer. Cancer cells have become more resistant to chemotherapy treatments. The aim of this review was to advance the association of microbes to cancer development among basic science researchers and clinical scientists in order to direct the processes to minimize the cancer epidemic. Furthermore, a view on a large number of microbes being observed in the areas of tumor than that of normal tissue is presented. Microbes can be identified in precancerous tissues, suggesting their presence before the induction of cancer; therefore they should be referred to as hidden killers. Overall, cancer development is caused by infected injuries by most fungi (Aspergillus species), viruses (human papillomaviruses), bacteria (Helicobacter pylori), and parasites (Schistosoma haematobium). There is minimal awareness on the relationship between cancer and microbes including their metabolites, especially in the developing world, which further increases the risk of cancer development by microbes that can be easily eradicated using basic drugs.
Changes in immunological pathways are involved in all stages of cancer. The immune system is composed of cells which are extremely sensitive to environmental changes. Antitumor immune response involves several pathways. The innate immune response is carried out by neutrophils, macrophages, eosinophils, mast cells, and natural killer (NK) cells, while the adaptive immune response is carried out by B-lymphocytes (B-cells) and T-lymphocytes (T-cells). Overall, lymphocytes act through the recognition of specific antigens circulating in the blood or on the cell surface. Connections between the innate and adaptive immune systems are made either by direct cell contact or by release of cytokines. Under normal conditions, inflammatory response is self-limiting because the production of pro-inflammatory cytokines (TH1 cytokines) is followed by generation of anti-inflammatory (TH2) cytokines such as interleukin (IL)-1, IL-10, or IL-13. Under special circumstances and defects in the resolution process or if its underlying factors continue, then inflammation will turn into chronic inflammation linked to increased risk of cancer. Chronic inflammation can increase the risk of cancer through promoting tumor initiation, the rate and extent of cell division, neovascularization, and angiogenesis. In addition, chronic inflammation results in an overload of reactive oxygen species (ROS), which, in turn, may lead to the development and progression of chronic diseases like cancer. Upregulation of cyclooxygenase (COX)-2, which is not expressed in most cells, may contribute to cancer development and progression through the release of prostaglandins (PGs). Signal transduction pathways like nuclear factor-kappa B (NF-κB) promote inducible expression of several proteins, such as cytokines, chemokines, acute-phase response proteins, cell adhesion molecules, antimicrobial peptides, inducible nitric oxide synthase (iNOS), and COX-2. Antitumoral immune response is mainly produced by T-cells to destroy tumor cells. However, immune escape mechanisms are a hallmark of tumor progression. Recent efforts have been devoted to develop small-molecule drugs that stimulate antitumoral immunity. While immunotherapy alone seems not to be sufficient to eradicate tumors, results of adjuvant immunotherapy are becoming ever more convincing. Bioactive dietary components that antagonize immune escape mechanisms would have potential to prevent tumor development or enhance tumor regression.
As of ancient times, fungi have been and still are a source of food and medicine. Dueto their nutraceutical value, they have been used to maintain and improve health, preserve youth and promote longevity. They are also a source of bioactive chemical compounds, which are, in turn, useful for the preparation ofnutriceuttical andpharmaceutical products.Of the 700 edible mushroom species investigated to date, only 50 have medicinal value. Among these 50 is Grifolafrondosawhich is one of the most thoroughly investigated, particularly as a stimulator of the immune system and for its antitumoralproperties. GrifolagargalSinger and G. sordulenta(Mont.) Singer, two representatives of the genus Grifola, in the andean patagonian forest in Argentina and Chile, have not been fully studied to date. Nor have their medicinal properties with their corresponding therapeutic applications been investigated. The purpose of this Ph. D. thesis was therefore to study the possibilities of cultivating G. frondosaunder control conditions. On the other hand, the medicinal activity observed in polypores, particularly in G. frondosa, gives support to the hypothesis on the presence of antioxidant and /or antigenotoxic activity in these species. Confirming such properties is absolutely necessary to conduct further research in favor of its medicinal properties and to promote the proposal of possible varieties of products derived from them, which would, in turn increase the value of these fungi.To further learn about the growth conditions of these species four campaigns were done in the oakforests located within Lanín National Park. With the help of mycologists and people living in the area, fruiting bodies were collected. Growth data and samples of rotting G. gargalwere also collected. Two new strains (strain B and G9) of G. gargalwere isolated, one from a standing tree and another from a fallen oak which had been producing fruitsfor a period longer than 20 years.Previous research on the history of oak forests reveals that during the last ice age they were fragmented, thus inducing the development of processes of genetic variability. Some of thesesources of variabilityvariables are the content and quality of certain polyphenolic compounds which are known to be important in the biology of fungal decomposers of wood. This could therefore be indicative of variability among different strains of oak woodlands to G. gargal. Two strains, corresponding to G. gargal(strain A) and G. sordulenta, were obtained fromthe Centro de Investigación y Extensión Forestal Andino Patagónico(CIEFAP).Reaching to the optimal conditions for the production of mycelium and fruiting bodies is key to the optimized production of compounds with nutritional, nutraceutical and also as a source for nutriceuticals and pharmaceuticals hypothetically present in these fungi. Analysis of mycelial growth of G. gargaland G. sordulentaon nutrient agar medium revealed that for both species, the best culture conditions were pH 4, 18 ° C and culture medium supplemented with 0.4% MYPA of sunflower husk powder.It thus took shorter time to obtain high quality seed and
21cultivation of strains in this medium was subsequently used routinely both for its maintenance and use as inoculum. Results were analyzed by a possible loss of vigour(after three years of subcultures) and showed that both strains did not lose vigourandthat there was a higher rate of colonization in Grifolasordulentawhich could be due to the fact that they adapted to the ingredients of the medium, thus indicating that the routine mycelium growingconditions followed were adequate to maintain its force for more than 12 subcultures.On the other hand, the increase in the contentofsunflower husk powder (0.4 %) did not alter the rate of colonization of strain A to G. gargal. This indicated that there is no need in increasingthe amount of this supplement in this species. It was also observed that there were no differences in the rate of colonization between strain A, B, and G9.It has been observed that in stock strains of mycology laboratories somestrains produce primordia and/or real fruitbodies after they are stored. This led usto use themethod of in vitroculture under controlled conditions to deep onthe processes underlying fungal morphogenesis, i.e the differentiation of vegetative myceliumto reproductive myceliumin these species.Observations of G. frondosa, G. gargaland G. sordulentaunder a magnifying glass and microscope were compared with observations by other researchers. These comparisons revealed some differences intaxonomic significance in terms of growth speed, colony morphology, colour changes in the culture medium and type of degradation studied in vitro.The comparison of the microscopic appearance of generative hyphae, gloeopleuras, skeletal, presence of chlamydospores and crystalloid structures with observations from other researchers showeddifferences which willcontribute to better understanding ofthe variability among strains of these species.The study of the in vitromorphogenic differentiationof G. gargaland G. sordulentawas useful as it helped detect changes in these crops after applying different light conditions. Irradiation withwhite light during the vegetative growth of G. gargalprevented a significant delay in growth of mycelium in Petri dishes, originated from unfavourbletemperatures (c.a. 21 º C). The different light conditions produced, in fact, changes in secondary metabolism and morphogenic differentiation of cultured mycelia.Compared to findings from a study conducted in colonies grown in Petri dishes which had completed their vegetative growth in darkness and had received a thermal shock, in our study the effect of these environmental conditions was greater on G. gargaland similar on G. sordulenta. This indicates that both species of Grifolaare sensitive to light irradiation with different morphogenic response type and intensity while white light is more effective.In the absence of light stimulus, both species of the genus were found to have the ability to show morphogenic events. In the case of G. gargal, strain A was observed to be more sensitive than B in the presentation of photomorphogenic responses. These results reported for different bandwidths of light irradiation are indicative of the involvement of more than one photoreceptor molecule.Grifola gargaland G. sordulentawere cultured in differential media containing different phenolic compounds in order to estimate ligninolytic ability in vitro.For comparative purposes and in order to extrapolate results to theircultivation, this study was carried out simultaneously with two other speciesofpoliporales which exhibit a good performance behave naturally in solid state
22fermentation whenusing sunflower husksas main substrate.The study revealed polyphenol oxidase enzyme expression at different times and with different growth patterns. It is suggested that one of these could be the enzyme lignin peroxidase (LiP). It was further verified the activity of laccases. Mn-peroxidase (MnP) activity was presumably presentbecause it was also detected in other strainsof G. gargaland because addition of Mn (II) increased the rate of colonization with G. gargalcultivation on sunflower husk as substrateand aspect was better in G. sordulenta.Growth of these species in differential media containing different carbohydrate sources was also studied in order to determine the activity of the enzyme cellobiose dehydrogenase. In all cases, growth ranged from moderate to low. It was found that G. gargalgrows best in xylulose and pectin, which could be indicaive of a preference for the hemicellulosic fraction of the substrates. In contrast, G.sordulentawas observed to grow well on cellulose and xylulose and evidenced cellulose dehydrogenase activity.Growth rate and density of colonization on media containing carbohydrates was higher in colonies of G. frondosaand Ganoderma lucidum, being even higher than those ofG. gargaland G. sordulentawhich, although they grew in all media, evidenced lower ability to colonizethem. Both studies in differential media showeda lower in vitroperformance, thus preannouncing a regular to low growth performance when these results were extrapolated to crop-based substrate sunflower husk.In some species the mycelium growing in liquid media have the advantage of reducing losses due to culture, the use of smaller spaces, and allow for an easy harvesting of the biomass and recovery of the metabolites dissolved in the medium. Cultures of G. gargaland G. sordulentawere carried out in agitated liquid medium using 250 and 500 ml Erlenmeyersflasks, and 3-liter bottles, as well as in liquid medium sources using 4-liter glasscontainers. Different systems were compared considering the work involved in each technique and the amount of biomass produced.Grifolagargalculture was carried out in 3-liter glass flasksand G. sordulentawas carried out in 250 ml Erlenmeyers flasks, yielding abiomass of 4 and 18 g/lafter 20 days of culture, respectively. In both species, optimum temperature for this crop was c.a. 18 °C. In this work it was alsodetermined that supplementation with different plant growth regulators and/or vitamins or aminoacids, or benzylaminopurine alone (0.1-10 mg/l) to the mediaof both species does not significantly increase biomass.Moreover, the use of homogenous innoculum reduced variability within treatments with respect to the use of disks of mycelium grown on agar as inoculum. The fungal material obtained from this work provided mycelial with different qualities to further test the antioxidant properties of these species.Grain spawn is the material used to inoculate large number of substratesin mushroom cultivation. The evaluation of mycelial growth of G. gargaland G. sordulentaby linear growth bioassay of Duncan (1997) revealed that both species can be cultivated in grains of wheat, sunflower, corn and wheat combinations with millet and corn with sunflower. It was alsoobservedthat optimum growth is achieved for both species when cultivation of wheat grains is in the pH range of 5.3 to 6.4.The full colonization of grains of wheat, following the production technique intraditional1 liter bottles, occurs more rapidly at 24 °C, compared with the growth of mycelium in semisolid media and liquid (c.a. 18 ° C). In grain cultivationthere were no differences in the number of bottles that completedthe
23colonization by days 25 and 30. For both species and for all types of grains, the largest proportion of substrates in bottles was colonized after 30 days. Considering the number of grains per gram of spawngrains, using wheat is best recommended.Duncan linear growth test was used to assess thesubstrate myceliacolonization rate, bulk density, increased protein content and laccase activity, and fiber degradation producedG. gargaland G. sordulentain 20 formulations based substrate sunflower husk. Another test was further conducted to study the effect of certain supplements on the colonization rate and apparent mycelial density in 10 formulations.Taken together, findings from our study support the conclusion that both species grow in these substrates, that sunflower seed husksneeds no supplements such as bran or Pleurotus ostreatusspent substrate to sustain regular growth of the mycelium.For G. gargalcolonization was found to improve with an acid treatment of the substrate or with the addition of enzyme cofactors (Mn (II) and Zn (II)), or other lignocellulosic sources such as oak, poplar, wheat straw. For G. sordulentacolonization was found to improve only in terms ofmycelialdensity with an acid treatment of the substrate, or with the addition of enzyme cofactors (NH4(I), Mn (II) and Zn (II)).The axenic culture of G. gargaland G. sordulentaon artificialsyntheticlogs using sunflower husksas substrate showed that both species can colonize the substrate, but with a longerproduction cycle and increased risk of contamination in relation to other mushroom species with the sametechnique. The thermal shock induction of 5 °C produced a significant induction of primordia and produced some fructifications.Gas exchange is crucial to the development of basidiomas, as expected based on previous research on the production of G. frondosa. The production sequence of both species at different stages is similar to that of G. frondosa: gray granular primordia thatgrow into fruitbodies ofbrainshape, then cauliflowershape and finally cluster flower.Theantioxidant properties of methanolic extracts of fruiting bodies, mycelium from liquid culture and/or wheat grains were analyzed in terms of their radical scavenger properties (DPPH radical) and reducing power. The content of phenolic compoundswas compared and methanol extracts were characterized using thin layer chromatography.It was thus possible to learn more about the properties of G. gargaland to confirm them for the first time in the case of G. sordulenta. These species have antioxidant reducing power properties. Different bioforms of mycelium and also different culture systems modify forms of qualitative and quantitative antioxidant content causing variations in radical scavenger activity and reducing power.In other words, the mycelium can be induced to change their antioxidant content using plant growth regulators and variability in the content of antioxidant property is independent of that produced in other antioxidant property. Antioxidant activity was found to be due in part to the presence of phenolic compounds but itwas not the only active compound. Thin layer chromatography also helped to show that the majority of antioxidant compounds were polar, in these were always revealed the presence ofphenolic compounds, and in some bands,also the presenseof flavonoids. Non-polar metabolites were observed in all chromatograms of extracts. In some cases they couldbe associated with phenolic compounds while in others could be associated to non-phenolic metabolites. In G. sordulentait was found that the antioxidant activity was preferentially associated to
24flavonoid compounds.Antigenotoxic properties of fruiting bodies and mycelia fromliquid cultures of G. gargal, as well as grains of wheat flour fermented with G. gargal, G. sordulentaand/or G. frondosawere also studied to test somatic mutation and recombination in Drosophila melanogaster. The chemical agent used to cause mutations (promutagen) was DMBA (7-12-dimethylbenz (α) anthracene). Research on toxicity revealed that treatment with DMBA increased larval mortality from 9 to 45%. Still, when fungal extracts were added larval mortality rate decreased.Both mutation and recombination were assessed as the number of white spots per hundred eyes, showing an increased frequency in the treatments with DMBA, and a decrease in co-treatments with both:DMBA and fungal extracts in the following order: G.gargalfruiting body, three grain mealscolonized and G. gargalliquid culture mycelium. It could be concluded that the material evaluated was not toxic and that in combination with procarcinogenic promutagenic DMBA both mortality and genotoxicity decreased.The protective response observed with fungal materials triggered detoxification mechanisms in D. melanogaster larvae which could be eitherdesmutagenic or bioantimutagenic and which could be produced due to some bioactive compounds present in higher fungi with antigenotoxic activity, such as phenolics, linoleic acid, polysaccharides and polypeptides.Summing up, findings on the absence of genotoxicity and antioxidant and antigenotoxic properties, in the fungal species studied in this Ph.D. thesis, will be greatly benefited from further research on the optimization of both speciesfor the production of fruiting bodies through fermentation in the solid state. In the meantime, the production of mycelia and metabolites in liquid culture medium is the alternative for such optimitization.A final section of this Ph.D. thesis includes information on the mineral content of different nutrients which were analyzed in samples of mycelium and fruiting bodies and colonized wheat grains. A novelty with biotechnological potential derived from this section concerns the obtention of wheat flour colonized by these fungi, which evidenced factibility of being used as functional nutrient.
Man consume mushroom because it is delicious. In the East, mushroom as medicine is not uncommon. Following encouraging outcome from clinical trials, several properties from edible and wild mushroom species have been recognised and registered as anticancer therapeutics. The drive to examine existing and wild mushrooms growing in each respective country for anticancer properties sees the compilation of new and unknown medicinal mushrooms research being shared for further assessment. The accumulated evidence of mushrooms possessing an anticancer property is attributed to all the extensive studies on cell lines, animal and human trials, validating the health, safety and quality of life after treatment. The move treads towards finding selective cytotoxicity mushroom properties which would only target cancerous cells and not harm normal healthy cells. The wealth of knowledge we have garnered for the last 20 years on how all macro fungi; be it edible, non-edible, poison or recreation mushrooms conceal in them the properties we could use to suppress the statistics of death and suffering due to cancer. Inevitably, the way forward next is to explore the potential of all wild and less commonly known mushroom resources and push these candidates down the pipeline for the next 20 years of further anticancer research, if not, potentials as food and delicacies.
Man consume mushroom because it is delicious. In the East, mushroom as medicine is not uncommon. Following encouraging outcome from clinical trials, several properties from edible and wild mushroom species have been recognised and registered as anticancer therapeutics. The drive to examine existing and wild mushrooms growing in each respective country for anticancer properties sees the compilation of new and unknown medicinal mushrooms research being shared for further assessment. The accumulated evidence of mushrooms possessing an anticancer property is attributed to all the extensive studies on cell lines, animal and human trials, validating the health, safety and quality of life after treatment. The move treads towards finding selective cytotoxicity mushroom properties which would only target cancerous cells and not harm normal healthy cells. The wealth of knowledge we have garnered for the last 20 years on how all macro fungi; be it edible, non-edible, poison or recreation mushrooms conceal in them the properties we could use to suppress the statistics of death and suffering due to cancer. Inevitably, the way forward next is to explore the potential of all wild and less commonly known mushroom resources and push these candidates down the pipeline for the next 20 years of further anticancer research, if not, potentials as food and delicacies.
Within the context of the quality strategy, the differentiation of the product quality of agricultural commodities, which can be achieved in either of the two spheres of sensory perception or health and safety, is of interest. Based on an analysis of the literature and expert surveys, 58 differentiation examples with a total of 81 subvariants were compiled. This collection shows farm managers, advisers, processors and distributors in particular that product differentiation is possible in many areas of the Swiss agricultural sector. Thirty-eight examples relate to sensory perception, with the focus in the plant production sphere – especially in the case of vegetables and fruit – being on unusual colours, sizes or flavour, whilst with animal husbandry, the constituents of the milk and flavour of the meat are relevant. The health and safety sphere is represented with 20 examples, inter alia with health-related constituents in grains, or high levels of polyunsaturated fatty acids in milk and meat owing to grassland-based feed. Although the majority of the examples are niche products, ten of them have managed the leap into the retail sector range. Greater cooperation along the entire value chain is essential in order to bring further examples into the retail trade and generate additional value-added.
Fourteen strains of Grifola frondosa (Dicks.) S. F. Gray, originating from different regions (Asia, Europe and North America) were tested for lignin degradation, ligninolytic enzyme activities, protein accumulation and exopolysaccharide production during 55 days of cultivation on oak sawdust. Lignin degradation varied from 2.6 to7.1 % of dry weight of the oak sawdust substrate among tested strains. The loss of dry matter in all screened fungi varied between 11.7 and 33.0%, and the amount of crude protein in the dry substrate varied between 0.94 to 2.55%. The strain, MBFBL 596, had the highest laccase activity (703.3 U/l), and the maximum peroxidase activity of 22.6 U/l was shown by the strain MBFBL 684. Several tested strains (MBFBL 21, 638 and 662) appeared to be good producers of exopolysaccharides (3.5, 3.5 and 3.2 mg/ml respectively).
За последние годы накопилось много данных об иммуноопосредованном и прямом воздействии биоактивных комплексов, продуцируемых грибами – высшими базидиомицетами на основные молекулярные мишени раковых клеток – TNF-индуцированном апоптозе, блокировке рецепторов EGF и VEGF, ингибировании циклинзависимых киназ и металлопротеиназ, связывании NF-κB.
В основном это слабые стимулы, на этапе прогрессии опухоли способные лишь усиливать основное лечение, хотя на этапе адъювантной терапии их роль возрастает.
Основным механизмом терапевтического воздействия грибных метаболитов является опосредованная естественными киллерными клетками (ЕКК) атака на неоплазмы, связанная со значительным снижением последними экспрессии антигенов главного комплекса гистосовместимости I типа (МНС1). Полисахариды клеточной стенки грибов ложно распознаются клетками врожденного иммунитета в качестве инвазивного клона микроорганизмов, поскольку у этой группы иммуноцитов сформирован целый класс рецепторов, настроенных на распознание молекулярных фрагментов самых разных клеточных стенок. Глюканы, маннаны, хитозан, являющиеся основными компонентами клеточных стенок грибов, выступают для иммунных клеток как один из «патоген-ассоциированных молекулярных образов», будучи комплементарными ряду рецепторов иммуноцитов (Toll-, dectin-1 рецепторы). Иммунная система распознает эти фрагменты и значительно активизируется. Поступающие в желудочно-кишечный тракт грибные полисахариды, не подвергаясь ферментативному разрушению, захватываются клетками слизистой оболочки кишечника и переносятся ими в подслизистый слой, где происходит их взаимодействие с рецепторами макрофагов и дендритных клеток, поглощающих, частично расщепляющих эти вещества и связывающих их фрагменты с молекулами МНС1. В селезенке и лимфатических узлах эти клетки стимулируют гранулоциты и ЕКК. В ходе контакта с раковыми клетками клетки-киллеры индуцируют либо Fas(ФНО)-зависимый апоптоз, либо неспецифический лизис клетки путем контаминации их цитолитическими гранулами, содержащими перфорин и гранзим B.
Повышение продукции ФНО целым рядом участников иммунного ответа создает фон, повышающий эффективность лекарственного воздействия на опухоль: наименее резистентная часть раковых клеток направляется на путь апоптоза, более резистентная – на путь аутофагии, и пролиферирующий пул, таким образом, существенно сокращается.
Тритерпеноиды (например, ганодеровые кислоты), эргостерол, клавилактоны, экстрагирующиеся вместе с грибными глюканами, ведут к G1/S и G2/M аресту клеточного цикла пролиферирующих клеток эпителия, в том числе умеренно-пролиферирующей злокачественной фракции. При сочетанном действии с химиопрепаратами такой арест выводит здоровые пролиферирующие клетки из-под лекарственной атаки, при этом раковые клетки с умеренно активными митогенными путями попадают под воздействие ЕКК. Сочетанное действие грибных экстрактов с химио- и радиотерапией достоверно увеличивает медиану выживаемости пациентов и улучшает качество их жизни.
Отдельно следует отметить полифенольные вещества, продуцируемые высшими базидиомицетами. Они представляют значительную емкость поглощения ионов, свободных радикалов, циркулирующих лигандов, будучи не токсичными для клетки. Продуценты полифенол-полисахаридных комплексов, например, чага (Inonotus obliquus f. sterilis) являются перспективным онкопревентивным средством.
Immune response to liver-specific lipoprotein (LSP) is involved in the pathogenesis of chronic active hepatitis. Experimental
hepatitis could thus be prepared in C57BL/6 mice by injection of liver-specific protein in a syngeneic liver homogenate with
Freund's complete adjuvant. In hepatitic mice treated with maitake (Grifola frondosa) fruit bodies, the values of glutamic oxaloacetic transaminase (GOT) and glutamic pyruvic transaminase (GPT) values increased
temporarily by 2.24–2.79 times and decreased rapidly thereafter. However, in the mice given normal feed, both values increased
constantly. Thus, we examined T cell activities both in the exacerbation and remission stages of hepatitis. We suggest that
the activation of CD8+ cells is more potentiated than that of CD4+ cells by administration of maitake or the D-Fraction-glucan (β-1,6 glucan having β-1,3 branches), which can enhance immuno-competent
cells at the exacerbation stage. However, at the remission stage, marked potentiation of CD8+ cell activity was not observed. These results suggest that depressed suppressor T cell activity is revived by the X-Fraction-glucan
(β-1,6 glucan having α-1,4 branched glucan), while the cytotoxic T cell activity, which is activated by the D-Fraction, is
restricted, thereby creating a smooth shift from the exacerbation stage to the remission stage.
The acid-insoluble, alkali-soluble, hot-water-extractable polymer (a polysaccharide containing approximately 30% of protein; D-fraction) obtained from the fruit bodies of Grifola frondosa (maitake) exhibited antitumor activities against allogenic and syngeneic tumors on oral administration to mice. Winn assay conducted to examine the tumor growth-suppressing effect revealed a complete inhibition of the tumor by the oral administration of D-fraction. This fact indicates that stimulation of the immune response system triggered by the tumor-bearing state is activated by D-fraction. Consequently, the activity of D-fraction on cells associated with immune response was examined. The cytolytic activity and interleukin-1 productivity of macrophages or T cells which exhibit antigen-specific cytotoxicity were enhanced. D-fraction was found to potentiate the delayed-type hypersensitivity response which is associated with tumor growth suppression.
A polysaccharide (3-branched β-1, 6-glucan MT-2) extracted from fruit bodies of Grifola frondosa (maitake) showed an antitumor effect against mouse syngeneic tumors (MM-46 carcinoma and IMC-carcinoma). It is not only directly activates various effector cells (macrophages, natural killer cells, killer T cells, etc.) to attack tumor cells, but also potentiates the activities of various mediators including lymphokines and interleukin-1. Thus, it acts to potentiate cellular functions and at the same time to prevent a decrease of immune functions of the tumor-bearing host.
A polysaccharide was extracted from fruit bodies of Grifola frondosa (maitake), and the chemical structure and antitumor activity were studied. The extracted polysaccharide could be hydrolyzed by ?A-glucanase into glucose, indicating it to be a β-glucan. The sample gave methyl 2, 3, 4, 6- tetra-Ο-, methyl 2, 4, 646-Ο-, methyl 2, 3, 4-tri -Ο- and methyl 2, 4-di-Ο-methylglucoside in the molar ratio of 4 : 2 : 1 : 4 on methylation. In the carbon-13 nuclear magnetic resonance spectrum, the signals of C-6' (related to (1-6) bonding) and C-3' (related to (1-3) bonding) were observed in addition to those of free C-6 and C-3. These results indicate that the major chain is made up of β-1, 6-linked glucose residues with branches of β-1, 3-linked glucose. This glucan inhibited the growth of Sarcoma 180 tumor in ICR mice.
The fruit body of Grifola frondosa (maitake), Basidiomycetes was confirmed to contain substances with anti-diabetic activity. When 1 g/d of powdered fruit body of maitake was given orally to a genetically diabetic mouse (KK-Ay), blood glucose reduction was observed, in contrast to the control group in which the blood glucose increased with ageing. Moreover, levels of insulin and triglyceride in plasma demonstrated a change similar to blood glucose with feeding of maitake. Ether-ethanol-soluble (ES) and hot water-soluble (WS) fractions were prepared from the fruit body and their hypoglycemic activity was examined. Blood glucose-lowering activity was found when ES-fraction or WS-50% ethanol float (X) fraction was administered orally, but other WS-fractions were inactive. These results suggest that the anti-diabetic activity was present not only in the ES-fraction consisting of lipid but also in the X-fraction of peptidoglycan (sugar:protein = 65:35).
Experimental rat models (5-week-old Sprague-Dawley rats) with hyperlipemia were prepared by feeding high-cholesterol feed containing sodium cholate and casein as a protein source. Dried maitake (Grifola frondosa) powder was mixed with the basic high-cholesterol feed and the serum lipids were periodically measured. Values of cholesterol, triglyceride and phospholipid in serum of rats in the maitake-feed group were suppressed by 0.3-0.8 times those in animals fed the basic feed, the latter values being close to those in rats given normal feed. The value of high density lipoprotein (HDL)-cholesterol in serum which is generally reduced by the ingestion of high-cholesterol feed remained the level it was at the beginning of the experiment. Weights of extirpated liver and epididymal fat-pads were significantly less (0.6-0.7 times) than those in the basic feed group, indicating that maitake inhibits lipid accumulation in the body. Liver lipids were also measured and the values were found to be decreased by maitake administration as true of serum lipid, suggesting maitake has an anti-liver lipid activity. Measurement of the amount of total cholesterol and bile acid in feces showed, the ratio of cholesterol-excretion had increased 1.8 times and bile acid-excretion 3 fold by maitake treatment. From these results, it is believed that maitake helps to improve the lipid metabolism as it inhibits both liver lipid and serum lipid which are increased by the ingestion of high-fat feed.
Anti-tumor action of fruit body of edible mushrooms orally administered to mice
- K Mori
- T Toyomatsu
- H Nanba
- Kuroda
Mori K, Toyomatsu T, Nanba H, Kuroda H. Anti-tumor action of fruit body of edible mushrooms orally administered to mice. Mushroom Sci 1987;XII:653-660.