Research Themes and Trends of Hen of the Woods or Maitake Medicinal Mushroom Grifola frondosa (Agaricomycetes): A Bibliometric Analysis of the Knowledge Field.

This paper aims to characterize the knowledge field of Grifola frondosa and analyze its research themes and trends. CiteSpace, a powerful bibliometric analysis tool, was adopted to visualize the knowledge field of G. frondosa research for facilitating this current study. A total of 747 articles and reviews retrieved from the Web of Science Core Collection (WoSCC) database between 1998 and 2022 were analyzed by CiteSpace. It was found that China and Japan are the most influential countries in G. frondosa research. Secondly, polysaccharide, bioactivity, structural characterization, and submerged culture are the main themes of G. frondosa research, among which bioactivity and structural characterization are the current research hotspots. Finally, selenium polysaccharide and gut microbiota may be the emerging trends in G. frondosa research in the future. This study could help researchers discern the evolution and future trends of G. frondosa research and provide a reference for related research work.

Maitake Medicinal Mushroom, Grifola frondosa (Agaricomycetes), and Its Neurotrophic Properties: A Mini-Review.

Neurodegeneration is one of the most common manifestations in an aging population. The occurrence of oxidative stress and neuroinflammation are the main contributors to the phenomenon. Neurologic conditions such as Alzheimer's disease (AD) and Parkinson's disease (PD) are challenging to treat due to their irreversible manner as well as the lack of effective treatment. Grifola frondosa (Dicks.: Fr.) S.F. Gray, or maitake mushroom, is believed to be a potential choice as a therapeutic agent for neurodegenerative diseases. G. frondosa is known to be a functional food that has a wide variety of medicinal purposes. Thus, this review emphasizes the neuroprotective effects and the chemical composition of G. frondosa. Various studies have described that G. frondosa can protect and proliferate neuronal cells through neurogenesis, antioxidative, anti-inflammatory, and anti-ß-amyloid activities. The mechanism of action behind these therapeutic findings in various in vitro and in vivo models has also been intensively studied. In this mini review, we also summarized the chemical composition of G. frondosa to provide a better understanding of the presence of nutritional compounds in G. frondosa.

Purification and characterization of Se-enriched Grifola frondosa glycoprotein, and evaluating its amelioration effect on As3+ -induced immune toxicity.

BACKGROUND: Selenium (Se)-enriched glycoproteins have been a research highlight for the role of both Se and glycoproteins in immunoregulation. Arsenic (As) is a toxicant that is potentially toxic to the immune function and consequently to human health. Several reports suggested that Se could reduce the toxicity of heavy metals. Moreover, more and more nutrients in food had been applied to relieve As-induced toxicity. Hence glycoproteins were isolated and purified from Se-enriched Grifola frondosa, and their preliminary characteristics as well as amelioration effect and mechanism on As3+ -induced immune toxicity were evaluated. RESULTS: Four factions, namely Se-GPr11 (electrophoresis analysis exhibited one band: 14.32 kDa), Se-GPr22 (two bands: 20.57 and 31.12 kDa), Se-GPr33 (three bands: 15.08, 20.57 and 32.78 kDa) and Se-GPr44 (three bands: 16.73, 32.78 and 42.46 kDa), were obtained from Se-enriched G. frondosa via DEAE-52 and Sephacryl S-400 column. In addition, Se-GPr11 and Se-GPr44 are ideal proteins that contain high amounts of almost all essential amino acids. Thereafter, the RAW264.7 macrophage model was adopted to estimate the effect of Se-GPr11 and Se-GPr44 on As3+ -induced immune toxicity. The results showed that the pre-intervention method was the best consequent and the potential mechanisms were, first, by improving the oxidative stress state (enhancing the activity of superoxide dismutase and glutathione peroxidase, decreasing the levels of reactive oxygen species and malondialdehyde); secondly, through nuclear factor-κB and mitogen-activated protein kinase-mediated upregulation cytokines (interleukin-2 and interferon-γ) secretion induced by As3+ . CONCLUSION: The results suggested Se-enriched G. frondosa may be a feasible supplement to improve health level of the As3+ pollution population. © 2021 Society of Chemical Industry.

Grifola frondosa may play an anti-obesity role by affecting intestinal microbiota to increase the production of short-chain fatty acids.

Background: Grifola frondosa (G. frondosa) is a fungus with good economic exploitation prospects of food and medicine homologation. This study aims to investigate the effects of G. frondosa powder suspension (GFPS) on the intestinal contents microbiota and the indexes related to oxidative stress and energy metabolism in mice, to provide new ideas for developing G. frondosa weight loss products. Methods: Twenty Kunming mice were randomly divided into control (CC), low-dose GFPS (CL), medium-dose GFPS (CM), and high-dose GFPS (CH) groups. The mice in CL, CM, and CH groups were intragastrically administered with 1.425 g/(kg·d), 2.85 g/(kg·d), and 5.735 g/(kg·d) GFPS, respectively. The mice in CC group were given the same dose of sterile water. After 8 weeks, liver and muscle related oxidative stress and energy metabolism indicators were detected, and the intestinal content microbiota of the mice was detected by 16S rRNA high-throughput sequencing. Results: After eight weeks of GFPS intervention, all mice lost weight. Compared with the CC group, lactate dehydrogenase (LDH) and malondialdehyde (MDA) contents in CL, CM, and CH groups were increased, while Succinate dehydrogenase (SDH) and Superoxide Dismutase (SOD) contents in the liver were decreased. The change trends of LDH and SDH in muscle were consistent with those in the liver. Among the above indexes, the change in CH is the most significant. The Chao1, ACE, Shannon, and Simpson index in CL, CM, and CH groups were increased. In the taxonomic composition, after the intervention with GFPS, the short-chain fatty acid (SCFA)-producing bacteria such as unclassified Muribaculaceae, Alloprevotella, and unclassified Lachnospiraceae increased. In linear discriminant analysis effect size (LEfSe) analysis, the characteristic bacteria in CC, CL, CM, and CH groups showed significant differences. In addition, some characteristic bacteria significantly correlated with related energy metabolism indicators. Conclusion: The preventive effect of G. frondosa on obesity is related to changing the structure of intestinal content microbiota and promoting the growth of SCFAs. While excessive intake of G. frondosa may not be conducive to the antioxidant capacity and energy metabolism.

Antitumor activities of Grifola frondosa (Maitake) polysaccharide: A meta-analysis based on preclinical evidence and quality assessment.

ETHNOPHARMACOLOGICAL RELEVANCE: The antitumor effects of Grifola frondosa/maitake polysaccharide (GFP) have been reported in many preclinical studies, especially in vivo experiments. The present meta-analysis aimed to provide an in vivo evidence and theoretical basis for future clinical trials by assessing the efficacy and underlying mechanisms of GFP in tumor treatment. MATERIALS AND METHODS: English and Chinese databases were examined to include animal experiments to study the antitumor activity of GFP. Literature screening, data extraction, and meta-analysis were conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. In addition, the Systematic Review Center for Laboratory animal Experimentation (SYRCLE) risk of bias (RoB) tool was used to assess the risk of bias of the included animal studies. RESULTS: Potentially relevant studies (442) were identified, and finally 24 eligible studies (all in English) were included. The meta-analysis revealed that GFP has significant effects in inhibiting tumor growth (high dose: mean difference (MD) = -1.34, 95% confidence interval (CI) = [-1.73, -0.95]; low dose: MD = -5.68, 95% CI = [-7.27, -4.09]), improving tumor remission rate (odds ratio = 25.59, 95% CI = [9.08, 72.11]), and enhancing immune function in both cellular (CD4+ T cell percentage: MD = 3.03, 95% CI = [1.16, 4.90]; CD8+ T cell percentage: MD = 1.10, 95% CI = [-0.29, 2.49]) and humoral immunity (MD and [95% CI] of interleukin (IL)-2, IL-12 and tumor necrosis factor-α were 7.86 [6.29, 9.44], 35.95 [5.18, 66.72], and 10.03 [8.71, 11.36], respectively), and the differences between the two groups of the above indicators were statistically significant (all P < 0.01) except CD8+ T cell percentage. Additionally, the quality of the included studies was not high, and the risk of bias mainly concentrated on selection, detection, and reporting biases. CONCLUSION: GFP is a potential candidate for tumor treatment and clinical trials. TRIAL REGISTRATION: The review protocol for this study was registered with the PROSPERO database before beginning the review process (CRD42018108897).

Medicinal Mushroom, Grifola gargal (Agaricomycetes), Lowers Triglyceride in Animal Models of Obesity and Diabetes and in Adults with Prediabetes.

Grifola gargal is a medicinal mushroom with biological effects, such as antiatherogenic activity, and is used as a treatment for various chronic inflammatory diseases. The aim of this study is to investigate the antidiabetic and antiobesity effects of a low-molecular weight hot water extract from G. gargal (GGL) against diabetes type 2. In a human clinical trial, 10 subjects with prediabetes consumed 9.2 g of GGL daily for 4 weeks. The significant beneficial health effects observed were decreases in triglyceride levels. This is the first report of these results in humans. Moreover, in animal experiments, we investigated the influence of administered feed with 2% (w/w) GGL for 42 days by using KK-Ay and ob/ob mice as animal models of obesity and diabetes. Results showed that GGL reduces blood glucose and triglyceride levels and adipose tissue. GGL (2.0 mg/mL) significantly suppressed the expression of the cytokine interleukin-6 in 3T3-L1 cells compared with control cells. Thus, the results indicate that G. gargal may be used as a safe and healthy medicinal food to prevent and improve diabetes- and obesity-related metabolic syndrome.

Antitumor, Anti-Inflammatory and Antiallergic Effects of Agaricus blazei Mushroom Extract and the Related Medicinal Basidiomycetes Mushrooms, Hericium erinaceus and Grifola frondosa: A Review of Preclinical and Clinical Studies.

Since the 1980s, medicinal effects have been documented in scientific studies with the related Basidiomycota mushrooms Agaricus blazei Murill (AbM), Hericium erinaceus (HE) and Grifola frondosa (GF) from Brazilian and Eastern traditional medicine. Special focus has been on their antitumor effects, but the mushrooms' anti-inflammatory and antiallergic properties have also been investigated. The antitumor mechanisms were either direct tumor attack, e.g., apoptosis and metastatic suppression, or indirect defense, e.g., inhibited tumor neovascularization and T helper cell (Th) 1 immune response. The anti-inflammatory mechanisms were a reduction in proinflammatory cytokines, oxidative stress and changed gut microbiota, and the antiallergic mechanism was amelioration of a skewed Th1/Th2 balance. Since a predominant Th2 milieu is also found in cancer, which quite often is caused by a local chronic inflammation, the three conditions-tumor, inflammation and allergy-seem to be linked. Further mechanisms for HE were increased nerve and beneficial gut microbiota growth, and oxidative stress regulation. The medicinal mushrooms AbM, HE and GF appear to be safe, and can, in fact, increase longevity in animal models, possibly due to reduced tumorigenesis and oxidation. This article reviews preclinical and clinical findings with these mushrooms and the mechanisms behind them.

Anti-diabetic effects of Grifola frondosa bioactive compound and its related molecular signaling pathways in palmitate-induced C2C12 cells.

ETHNOPHARMACOLOGICAL RELEVANCE: Grifola frondosa (GF), a high value medicinal mushroom, is popularly consumed as traditional medicines and health foods in China and Japan. It is a herbal medicine traditionally used for treating inflammation, cancer and diabetes. AIM OF THE STUDY: This study aimed to examine the anti-diabetic effects of a GF bioactive compound ergosterol peroxide (EPO), and its mechanism(s) of action in palmitate (PA)-induced C2C12 cells. MATERIALS AND METHODS: EPO was isolated and purified from GF fruiting bodies, and used to test for anti-diabetic activity in PA-induced murine C2C12 skeletal muscle cells through measuring glucose uptake, intracellular ROS production, and expressions of MAPKs, IRS-1, PI3K, Akt and GLUT-4 proteins. RESULTS: EPO significantly up-regulated glucose absorption and increased cell growth. At 5 µM, EPO significantly enhanced glucose uptake and decreased ROS formation, as well as up-regulated the expression of IRS-1, p-IRS-1, PI3K, Akt, p-Akt, and GLUT-4 proteins in PA-induced cells, while their p-JNK and p-p38 expression were down-regulated. GLUT-4 siRNA treatment effectively down-regulated the EPO-induced absorption of glucose and inhibited the expression of GLUT-4. CONCLUSION: These results suggest that the anti-diabetic effect of GF was from its bioactive compound EPO through the inhibition of ROS production, up-regulation of glucose absorption, and modulation of PI3K/Akt, MAPKs and GLUT-4 signaling transduction pathways.

Influence of Maitake (Grifola frondosa) Particle Sizes on Human Mesenchymal Stem Cells and In Vivo Evaluation of Their Therapeutic Potential.

Maitake (Grifola frondosa) mushroom has received an enormous amount of attention as a dietary supplement due to its high nutritional values. The particle sizes of G. frondosa mushrooms were monitored by a classifying mill. ß-Glucans are the bioactive component of the mushroom, and it was revealed through Fourier transform infrared spectroscopy (FTIR), proton and carbon nuclear magnetic resonance (1H and 13C-NMR), matrix-assisted laser desorption/ionization, and time-of-flight (MALDI-TOF) spectrometry. The biocompatibility of G. frondosa particles, as well as induced osteogenesis of hMSCs, was evaluated through WST-1 assay and alizarin staining (ARS) technique, respectively. Notably, enhanced cell viability was noted in the presence of G. frondosa. Significantly improved calcium deposition has observed from hMSCs with G. frondosa, suggesting to their mineralization potential. The expression of osteogenic related gene markers was examined in the presence of G. frondosa through real-time polymerase chain reaction (qPCR) technique. The upregulation of osteogenic gene markers in the presence of G. frondosa particles was indicating their superior osteogenic potential. Besides, G. frondosa also activated the secretion of various kinds of proteins from the hMSCs indicating their potential for tissue engineering applications. Enhanced secretion of different immunoglobulins was observed in rat serum in the presence of G. frondosa, further demonstrating their therapeutic nature. Therefore, G. frondosa is effective for enhanced osteogenesis and can be utilized as a natural, edible, and osteogenic agent.

A ß-glucan from Grifola frondosa effectively delivers therapeutic oligonucleotide into cells via dectin-1 receptor and attenuates TNFα gene expression.

Grifola frondosa is an edible and medicinal mushroom with great nutritional values and bioactivities. In the present study, a soluble homogeneous ß-glucan, GFPS, with high molecular mass of 5.42 × 106 Da was purified from the fruit bodies of Grifola frondosa using 5% cold NaOH. The structure of GFPS was determined with FT-IR, NMR, and monosaccharide composition analysis, and was identified to be a ß-D-(1-3)-linked glucan backbone with a single ß-D-(1-6)-linked glucopyranosyl residue branched at C-6 on every third residue. Our results indicated that GFPS had a triple helical structure and could form complex with polydeoxyadenylic acid (poly[A]). Further studies demonstrated that GFPS could interact with poly[A] moiety of a designed antisense oligonucleotide (ASO) targeting the primary transcript of proinflammatory cytokine TNFα (TNFα-A60). This GFPS-based complex could incorporate TNFα-A60 into the macrophage cells via dectin-1 receptor and attenuate lipopolysaccharide-induced secretion of TNFα. Our results suggested that GFPS could be applied to deliver therapeutic oligonucleotides for the treatment of diseases such as inflammation and cancers.

Relationship between heat treatment on structural properties and antitumor activity of the cold-water soluble polysaccharides from Grifola frondosa.

Grifola frondosa is a basidiomycete fungus with potential biomedical applications owing to the presence of bioactive polysaccharides. The activities of polysaccharides are influenced by many factors, particularly temperature; however, the optimal temperature and conditions for preparation of polysaccharides from this organism have not yet been determined. Therefore, in this study, cold-water soluble polysaccharides from Grifola frondosa were extracted at 4 °C (GFP-4) and purified. GFP-4-30, GFP-4-60 and GFP-4-90 were obtained from GFP-4 after treatment at 30 °C, 60 °C, or 90 °C, respectively, for 6 h. MTT results showed that GFP-4 had the highest inhibitory effects on the proliferation of SPC-A-1 cells in vitro. High-performance gel permeation chromatography results demonstrated that the molecular weight of GFP-4 was 1.05 × 106 Da and that GFP-4-30, GFP-4-60, and GFP-4-90 showed different levels of degradation and generated small molecule sugars. Fourier transform infrared spectroscopy, gas chromatography, and nuclear magnetic resonance results indicated that GFPs mainly consisted of α-D-Galp, α-D-Manp and α-D-Glcp. Periodate oxidation, Smith degradation, and methylation results showed that the backbones of the molecules consisted of 1,3-linked-Galp. After heat treatment, percentages of (1 → 3,4) α-D-Galp in heat-treated polysaccharides were obviously decreased, indicating their lower branching degree, and resulting in weaker antitumor effects. Overall, our findings demonstrated changes in the structure-activity relationships of GFP-4 after heat treatment and provided a theoretical basis for the application of GFP-4 in the food and drug industries.

Antioxidative and Immunomodulatory Activities of the Exopolysaccharides from Submerged Culture of Hen of the Woods or Maitake Culinary-Medicinal Mushroom, Grifola frondosa (Agaricomycetes) by Addition of Rhizoma gastrodiae Extract and Its Main Components.

Grifola frondosa (hen of the woods or maitake) is a famous culinary-medicinal mushroom, and its exopolysaccharides (EPSs) have biological activities with or without supplementation with exogenous additives. In this study, a Rhizoma gastrodiae extract was added to a G. frondosa fermentation system. P-hydroxylbenzaldehyde (HBA), the main product of R. gastrodiae, had the highest utilization rate in the fermentation process (42%). In addition, the EPSs of G. frondosa after addition of R. gastrodiae extract (REPS), of HBA (HEPS), or of a standard solution according to the main component ratio of R. gastrodiae extract (CEPS) were obtained. We then determined the antioxidant and immunomodulatory activities of EPS, REPS, HEPS, and CEPS. Overall, REPS showed the highest antioxidant activities compared with EPS and HEPS (P < 0.05) but similar to that of CEPS (P > 0.05). The half-inhibitory concentration (ED50) values of REPS (< 4 mg/mL) were lower than those of EPS, HEPS, and CEPS. Moreover, REPS was better able to stimulate phagocytosis and nitric oxide production of RAW 264.7 macrophages than were the others, without a significant difference from CEPS (P > 0.05). An interesting and important finding is that a R. gastrodiae extract can increase antioxidant and immunomodulatory activities of EPS preparations from G. frondosa, and the standard solution of the main components of the R. gastrodiae extract may be better for simulating fermentation performed by G. frondosa and biological activities of its major products.

Grifola frondosa extract and ergosterol reduce allergic reactions in an allergy mouse model by suppressing the degranulation of mast cells.

The increasing number of patients suffering from allergic diseases is a global health problem. Grifola frondosa is an edible mushroom consumed as a health food in Asia, and has recently been reported to have anti-allergic effects. We previously reported that G. frondosa extract (GFE) and its active components, ergosterol and its derivatives, inhibited the antigen-induced activation of RBL-2H3 cells. Here, we demonstrated that GFE and ergosterol also had an inhibitory effect on the degranulation of bone marrow-derived mast cells (BMMCs) and alleviated anaphylactic cutaneous responses in mice. Using an air pouch-type allergic inflammation mouse model, we confirmed that oral administration of GFE and ergosterol suppressed the degranulation of mast cells in vivo. Our findings suggest that G. frondosa, including ergosterol as its active component, reduces type I allergic reactions by suppressing mast cell degranulation in mice, and might be a novel functional food that prevents allergic diseases.

Grifola frondosa polysaccharides ameliorate lipid metabolic disorders and gut microbiota dysbiosis in high-fat diet fed rats.

The purpose of this study was to assess the potential effects of polysaccharides from edible mushroom Grifola frondosa (GFP) on lipid metabolic disorders and gut microbiota dysbiosis, and elucidate their possible regulatory mechanisms on lipid and cholesterol metabolism in high-fat diet (HFD)-exacerbated hyperlipidemic and hypercholesterolemic rats. Results showed that oral administration of GFP markedly alleviated dyslipidaemia through decreasing the serum levels of total triglycerides, total cholesterol, and free fatty acids, and significantly suppressing hepatic lipid accumulation and steatosis. Besides, the excretion of fecal bile acids was also promoted by oral administration of GFP. Metagenomic analysis revealed that GFP supplementation (400 mg kg-1 day-1) resulted in significant structure changes on gut microbiota in HFD-fed rats, in particular modulating the relative abundance of functionally relevant microbial phylotypes compared with the HFD group. Key microbial phylotypes responding to GFP intervention were identified to strongly correlate with the lipid metabolism disorder associated parameters using the correlation network based on Spearman's correlation coefficient. Serum and hepatic lipid profiles were found positively correlated with Clostridium-XVIII, Butyricicoccus and Turicibacter, but negatively correlated with Helicobater, Intestinimonas, Barnesiella, Parasutterella, Ruminococcus and Flavonifracter. Moreover, GFP treatment (400 mg kg-1 day-1) regulated the mRNA expression levels of the genes responsible for hepatic lipid and cholesterol metabolism. Oral supplementation of GFP markedly increased the mRNA expression of cholesterol 7α-hydroxylase (CYP7A1) and bile salt export pump (BSEP), suggesting an enhancement of bile acid (BA) synthesis and excretion from the liver. These findings illustrated that GFP could ameliorate lipid metabolic disorders through modulating specific gut microbial phylotypes and regulating hepatic lipid and cholesterol metabolism related genes, and therefore could be used as a potential functional food ingredient for the prevention or treatment of hyperlipidemia.

Preparation of a novel Grifola frondosa polysaccharide-chromium (III) complex and its hypoglycemic and hypolipidemic activities in high fat diet and streptozotocin-induced diabetic mice.

Polysaccharide from Grifola frondosa is one of the best metal-ion chelating agents because of its structural characteristics and excellent functional activities. In this study, we synthesized and characterized a novel Grifola frondosa polysaccharide-chromium (III) [GFP-Cr(III)] complex. Response surface methodology (RSM) was used to optimize the reaction conditions for the maximum chelation rate of GFP-Cr(III) complex. The optimal reaction conditions obtained from RSM were as follows: concentration of CrCl3 6.97 mg/mL, pH 7.75 and temperature 71.73 °C, respectively. The pH was the most significant factor, followed by reaction temperature and concentration of CrCl3. Under the deduced optimal conditions (CrCl3 7.0 mg/mL, pH 7.7 and temperature 70.0 °C), the experimental chelation rate was 28.01% ±â€¯0.18% for GFP-Cr(III) complex, which agreed closely with the predicted value (27.61%). Fourier transform infrared (FTIR) spectroscopy revealed that the primary sites of chromium (III)-binding in polysaccharides were OH and CN groups, leading to the structure of GFP-Cr(III) complex was loose than the original polysaccharide. Nevertheless, Cr(III) did not make a fundamental change in the structure of GFP when comparing the FTIR spectra of GFP and GFP-Cr(III) complex. Additionally, the effects of GFP-Cr(III) complex on hyperglycemia and hyperlipidemia in high-fat diet (HFD) and streptozotocin (STZ)-induced diabetic mice were also investigated. Results showed that the serum total cholesterol (TC), total triglyceride (TG), low density lipoprotein cholesterol (LDL-C), fasting blood glucose levels and glucose tolerance in diabetic mice fed a high-fat diet (HFD) supplemented with GFP-Cr(III) complex (900 mg/kg day) were significantly lower than the diabetic group (P < 0.01). These results suggest that GFP-Cr(III) complex could be used as potential functional food ingredients for the prevention or treatment of hyperglycemia and hyperlipidemia.

Effects of Heat Treatment on the Structural Characteristics and Antitumor Activity of Polysaccharides from Grifola frondosa.

This study investigated the effects of heat treatment on structural characteristics and in vitro antitumor activity of polysaccharides from Grifola frondosa. GFP-4 (extracted at 4 °C), GFP-4-80 (80 °C treatment on GFP-4) and GFP-80 (extracted at 80 °C) were prepared, and the chemical composition analysis showed that their total sugar contents were all higher than 90%, high-performance gel-permeation chromatography (HPGPC), ion chromatography (IC) and Fourier-transform infrared spectroscopy (FTIR) results demonstrated that GFP-4 were degraded and denatured after 80 °C heat treatment, MTT and JC-1 results showed that GFP-4 exhibited higher inhibitory effects on HepG2 cells in vitro than GFP-4-80 and GFP-80. Our study suggested that heat treatment at 80 °C on polysaccharides from Grifola frondosa would destroy their structure and attenuate their antitumor effects.

Maturation of dendritic cells by maitake α-glucan enhances anti-cancer effect of dendritic cell vaccination.

Dendritic cells (DCs) play a primary role in antigen presentation to CD4+ and CD8+ T cells and induce acquired immune response against cancer cells. Therefore, determining positive modulators of DC activation to improve therapeutic approaches for cancer immunotherapy is greatly needed. In this study, we investigated the effect of maitake α-glucan YM-2A, isolated from Grifola frondosa, on the maturation and function of DCs and its adjuvant effect on a tumor-associated antigen (TAA)-loaded DC vaccine against murine tumor. We showed that YM-2A induced morphological changes and increased cell-surface maturation markers and cytokine production in DCs. In a mixed lymphocyte reactions assay, YM-2A-treated DCs increased proliferation and production of IFN-γ by allogeneic CD4+ and CD8+ T cells. These results indicate that YM-2A phenotypically and functionally activates DCs. Furthermore, YM-2A-treated TAA-loaded DC vaccine significantly reduced tumor growth and improved survival in two murine tumor models, CT-26 tumor-bearing BALB/c mice and B16 melanoma-bearing C57BL/6 mice. YM-2A-treated TAA-loaded DC vaccine increased splenic IFN-γ producing CD4+ and CD8+ T cells in CT-26 tumor-bearing BALB/c mice. Antibody neutralization studies indicated that YM-2A-induced DC maturation is mediated, in part, by the Dectin-1-dependent pathway. Overall, YM-2A-treatment with a TAA-loaded DC vaccine could be an excellent candidate for immunotherapy against cancer.

A Polysaccharide Extract from Maitake Culinary-Medicinal Mushroom, Grifola frondosa (Agaricomycetes) Ameliorates Learning and Memory Function in Aluminum Chloride-Induced Amnesia in Mice.

Maitake (Grifola frondosa) is an edible mushroom exhibiting high nutritional value in terms of containing health-beneficial bioactive compounds. Previously, we reported that a protein-bound polysaccharide bioactive component of G. frondosa (PGM) could enhance the expression of α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptor (AMPAR), which is critical for learning and memory. However, the potential benefits of PGM on learning and memory function have never been investigated. In the current study, we aimed to explore the beneficial effect of PGM on learning and memory function in aluminum chloride (AlCl3)-induced amnesia in mice and to explore the underlying mechanisms. Mice were intraperitoneally administered with AlCl3 (60 mg/kg/d) and PGM (5, 10, or 20 mg/kg/d) for 6 weeks consecutively, and then the Morris water maze (MWM) test was conducted to assess the learning and memory function. Hematoxylin-eosin staining was performed to observe the morphology of neurons in the hippocampal dentate gyrus (DG). The expression of p-Tau (Ser396), Tau, p-GluA1 (S845), GluA1, and brain-derived neurotrophic factor (BDNF) proteins was evaluated with western blot. We found that PGM (5 and 10 mg/kg/d) significantly improved learning and memory function and attenuated histopathological abnormalities in the hippocampal DG region in the AlCl3-treated mice. Furthermore, PGM treatment significantly enhanced the level of AMPAR and BDNF in the hippocampus, while suppressing the tau protein hyperphosphorylation at the Ser396 site. These findings indicated that PGM could significantly attenuate the AlCl3-induced amnesia through the synergistic action of its active component on tau pathology, AMPAR and BDNF signaling pathway.

[Meta-analysis on effect of Grifola frondosa polysaccharide in regulating in vivo immunoregulatory function on animal disease models].

The study aimed to explore the in vivo immunoregulatory function of Grifola frondosa polysaccharide( GFP) on animal disease models. Databases of PubMed,Embase,Web of Scinece,CNKI,CBM and Wan Fang Data were searched from the date of their establishment to February 2018. Two reviewers independently screened included studies and evaluated their quality by using SYRCLE's risk of bias tool. R software was used to analyze the data. Finally,20 animal experiment studies were included. According to Metaanalysis. For cellular immunity,GFP could effectively enhance the proliferation of effect or T cells,natural killer cells and macrophages in mice. The percentage of CD4+T cells( MD = 1. 89,95% CI [0. 94,2. 83],P < 0. 000 1),CD8+T cells( MD = 8. 46,95% CI[5. 93,11. 00],P<0. 000 1),NK cells( MD= 2. 67,95% CI [0. 23,5. 11],P= 0. 03),and macrophages( MD= 14. 09,95% CI[0. 84,27. 34],P= 0. 04) were all higher than those in control group. For humoral immunity,GFP could increase the secretion of TNF-α and INF-γ． The secretion of TNF-α( SMD = 15. 92,95% CI [9. 07,22. 76],P<0. 000 1) and INF-γ( SMD = 5. 34,95% CI[3. 42,7. 26],P<0. 000 1) were all higher than those in control group. In conclusion,GFP could regulate immunologic function by enhancing the proliferation activity of immune cells( CD4+T cells,CD8+T cells,NK cells and macrophages) and the secretion of immune factors( TNF-α and INF-γ) ． However,it is necessary to further standardize the selection of specific surface markers of immune cells and the administration of GFP,in order to reduce the heterogeneity among the studies. At the same time,more attention shall be paid to experimental design,implementation and full report,especially to the establishment and implementation of animal experimental registration system,so as to improve the transparency and quality of the whole process of animal experimental research,enhance the value of basic research ultimately,and provide a reliable theoretical basis for the transformation of basic research into clinical research.

Effect of Grifola frondosa 95% ethanol extract on lipid metabolism and gut microbiota composition in high-fat diet-fed rats.

This study aimed to investigate the effects of 95% ethanol extract of G. frondosa (GF95) on lipid metabolism and gut microbiota composition in high-fat diet (HFD) fed rats. UPLC/Q-TOF MS indicated that GF95 was enriched with flavones, fatty acids and so on. Meanwhile, we found that body weight, serum lipid or liver index (total cholesterol, triglyceride, and low density lipoprotein cholesterol) levels were significantly decreased in GF95-treated HFD-fed rats. Furthermore, GF95 treatment regulated mRNA expression levels involved in lipid metabolism. GF95 consumption significantly enhanced the excretion of bile acids in the cecum. Besides, in this study, a higher abundance of Butyricimonas genus was revealed in the GF95 group, which is highly related to the highest production of short-chain fatty acids in the caecum contents among the experimental groups. Interestingly, results from network analysis showed that Butyricimonas were negatively correlated with serum and liver lipid profiles.