Meta-analysis on effect of Grifola frondosa polysaccharide in regulating in vivo immunoregulatory function on animal disease models / 中国中药杂志

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.

Enrichment of flavonoid aglycones in licorice extract enhanced anti-inflammatory potential,but its hypnotic effect was not altered / 中国药理学与毒理学杂志

OBJECTIVE Licorice is used throughout the world as a traditional herbal remedy. Ac-cording to Chinese traditional medicine licorice alone can be used to treat inflammation.Although there have been some studies investigated the anti-inflammatory ingredients of licorice, but for the potency of flavonoid glycoside and their aglycones on inflammation are not evaluated.This study was designed to assess the contributions of licorice flavonoid glycosides and their aglycons to its anti-inflammatory and hypnotic effects. METHODS For the flavonoid aglycone's enrichment, the extract of licorice (EL) was fermented in submerged culture of the edible fungus Grifola frondosa HB0071 mycelia which can produce β-glucosidase and catalyze the flavonoid glycosides to aglycones.EL and fermented extract of licorice (FEL) were used in this study. The anti-inflammation test was carried out in arachidonic acid (AA)-induced ear edema model and the hypnotic test was performed by using electroencephalogram (EEG)analysis method in normal freely moving SD rats.The chemicals constituents were analyzed by HPLC.RESULTS During fermentation,the falvonoid glycosides of licorice were hydrolyzed by the time process.Along with fermentation time,the concentration of the major flavonoid glycosides,liquiritin and isoliquiritin were decreased obviously, and simultaneously their aglycons, liquiritigenin and isoliquiriti-genin were remarkably increased in FEL.Moreover,the content of another major constituent glycyrrhi-zic acid and glycyrrhetinic acid were not changed after the fermentation. In AA-induced mice ear ede-ma test,after topical application,FEL(effective dose range:5-20 μg·ear-1)showed more potent inhibito-ry activity than EL(effective dose range:25-100 μg·ear-1).On the other hand,oral administration of EL and FEL exhibited the same hypnotic potency and both enhanced the total sleep time including rapid eye movement (REM) sleep and non-REM sleep time. CONCLUSION These results suggested that the enrichment of flavonoid aglycons such as liquiritigenin and isoliquiritigenin enhanced the anti-inflam-matory potency of licorice extract,and this potentiation has nothing to do with glycyrrhizic acid or glycyr-rhetinic acid.In addition,enrichment of flavonoid aglycones did not alter the hypnotic effect of licorice.

Structure and immunomodulatory activity of extracellular polysaccharide from Grifola frondosa / 生物工程学报

We aimed at analyzing the structure of extracellular polysaccharide A from Grifola frondosa (EXGFP-A) and testing its immunomodulatory activity. Structural analysis shows that EXGFP-A was a contained α-D-glucoside bond and pyranose ring. GC analysis reveals that EXGFP-A was mainly composed of rhamnose, arabinose, xylose, mannose, glucose, galactose, by the molar ratio of 0.28:0.31:0.30:0.06:7.98:0.61. The results of MTT(3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay indicates when EXGFP-A was at a concentration of 80 μg/mL and treatment time of 48 h, RAW264.7 cells proliferation index reached a maximum of 137.5%. Meanwhile, the AO staining showed that EXGFP-A activated RAW264.7 cells and improved the level of intracellular nucleic acid metabolism. In addition, in a certain range of concentration, EXGFP-A was able to increase the release of NO in RAW264.7 cells, and upregulate the mRNA expression of immunological factor TNF-α, IL-1β, IL-6, IL-12, IFN-γ and iNOS of RAW264.7 cells. Our results confirm that EXGFP-A had immunomodulatory activity. Our findings provided scientific basis for the structural analysis and application of Grifola frondosa polysaccharide.

Immunomodulatory activity of macromolecular polysaccharide isolated from Grifola frondosa / 中国天然药物

The present study was designed to evaluate the immune-modulating effects of the polysaccharide from Grifola frondosa (GFP) by using mouse peritoneal macrophage and cytoxan (CTX) induced immunosuppression models. Our results from the phagocytotic and mononuclear phagocytic system function assays showed that GFP-A (one component from GFP) stimulated the phagocytosis of the phagocytes. The splenocyte proliferation assay showed that GFP-A acted the effect combing ConA or LPS in splenocyte proliferation. The results showed that GFP-A increased indices of thymus and spleen, the levels of LDH and ACP in the spleen, the mRNA levels of IL-1β, IL-2, IL-6 and IFN-γ in splenocyte. And GFP-A also significantly increased the expression of CD4(+) and CD8(+) splenic T lymphocytes, which were suppressed by the CTX in peripheral blood. In conclusion, our results indicate that the GFP-A is involved in immunomodulatory effects leading to its modulatory effects on immunosuppression.

Anti-hepatocellular carcinoma effects of Grifola frondosa extract and its underlying mechanisms / 中国药学杂志

OBJECTIVE: To investigate the anti-hepatocellular carcinoma effect and underlying mechanisms. METHODS: In PLC/PRF/5 and HepG2, after treatment with Grifola frondosa extract, MTT method, chemical method, JC-1 staining and Western Blot were applied to determine cell viability, caspase 3 activity, mitochondrial membrane potential, the expression of Bcl-2 and Bax, and the phosphorylation of Akt/GSK3β. The anti-tumor activity of Grifola frondosa extract was further confirmed in PLC/PRL/5-xengrafted mice model. RESULTS: Grifola frondosa extract significantly reduced cell viability, mitochondrial membrane potential, the expression of Bcl-2 and the phosphorylation of Akt/GSK3β, and enhanced LDH release, caspase 3 activity and the expression of Bax in both PLC/PRF/5 and HepG2 cells. 12-day Grifola frondosa extract treatment significantly inhibited the PLC/PRF/5-xenografted tumor growth without influence the body weight of mouse. CONCLUSION: All these data indicate that Grifola frondosa extract-mediated anti-hepatocellular carcinoma effects are related to its modulation of the activations of Akt/GSK3β and mitochondrial pathway.

Grifola frondosa Extract Induced Acute Hepatic Injury.

Aim: To describe a case of acute hepatic injury related to the use of Grifola frondosa in a patient with colon cancer. Case Presentation: Patient is a 67 year old female with stage IV poorly differentiated adenocarcinoma of the colon, who presented with epigastric pain one month after resection of her primary tumor. A staging PET scan revealed metastasis to regional lymph nodes without solid organ involvement. Her home medications include longstanding amlodipine and losartan, and a recently started Grifola frondosa derivative. Her laboratory data was significant only for acute transaminitis (AST:967 U/L, ALT:768 U/L) without hyperbilirubinemia. Alcohol, acetaminophen, and a viral panel (EBV, CMV, hepatitis A/B/C) were all negative. A CT scan revealed heterogenous liver parenchyma without focal lesions. A subsequent liver biopsy demonstrated active portal inflammation with eosinophilic infiltration. Discussion: The etiologies of significant acute transaminitis include viral hepatitis, ischemic liver injury, acetaminophen toxicity and drug-induced liver injury (DILI). Viral and ischemic hepatitis and acetaminophen toxicity were excluded based on laboratory analysis and imaging studies. Liver biopsy findings demonstrating the characteristic eosinophilic infiltration of a drug reaction favored DILI as the etiology of transaminitis in this case. With a RUCAM score of 7 calculated based on history, clinical course, and objective data, DILI was concluded to be probably attributed to the patient’s recent use of the Grifola frondosa extract. Conclusion: A diagnosis of drug induced liver injury probably secondary to the use of Grifola frondosa extract was made after excluding all other causes of significant acute transaminitis.

Effects of Grifola frondosa Polysaccharide on T cell Subsets and Th1/Th2 Subsets of Spleen Deficiency Mice / 中国中医药信息杂志

Objective To observe the effects of Grifola frondosa polysaccharide on T cell subsets and Th1/Th2 subsets of spleen deficiency mice, and investigate its immunoregulation mechanism. Methods Forty-eight KM mice were divided into 6 groups:normal group, spleen deficiency group, positive group (lentinan), three dosage groups of Grifola frondosa polysaccharide, 8 mice in each group. The mice were injected corresponding drug intraperitoneally for 10 days. Then mice in each group were detected CD3+, CD4+ and CD8+T cell by flow cytometry. IFN-γ and IL-4 levels were detected by ELISA. Results The high dose of Grifola frondosa polysaccharide could significantly increase the CD4+T lymphocytes percentage in peripheral blood (P<0.05). Medium and high dose of Grifola frondosa polysaccharide could significantly increase CD4+/CD8+T cell ratio (P<0.01) and CD3+T lymphocyte percentage (P <0.01) of spleen deficiency mice. Medium and high dose of grifola frondosa polysaccharide could significantly increase IFN-γ level in serum of spleen deficiency mice (P<0.01), and high dose of Grifola frondosa polysaccharide could decrease IL-4 level in serum of spleen deficiency mice (P<0.01). Conclusion Grifola frondosa polysaccharide can improve the decreased CD4+/CD8+T cell ratio which caused by spleen deficiency, and promote the transformation of Th1 to Th2, thus treating spleen deficiency syndrome.

Lignin degradation, ligninolytic enzymes activities and exopolysaccharide production by Grifola frondosa strains cultivated on oak sawdust

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 percent 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 percent, and the amount of crude protein in the dry substrate varied between 0.94 to 2.55 percent. 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).

Effect of Hericium erinaceum (Yamabusitake) and Grifola frondosa (Maitake) on the Suppression of EL4-Tumor Cell Growth / 日本補完代替医療学会誌

The objectives of this study were to investigate the effects of <i>Hericium erinaceum</i> (Yamabusitake) and <i>Grifola frondosa </i>(Maiteke) on the proliferation for EL4-tumor and immunoregulatory function by flow cytometory.<br> It was found that Yamabushitake and Maitake tend to inhibit the proliferation of EL4-tumor individually. In the flow cytometory analysis, Maitake-treatment showed the preserve effect against the depression effect by bearing EL4-tumor on cytotoxic T cell and NK-cell from spleen cell. This effect was shown more clear in the group of mixture Yamabusitake and Maitake.<br>

Determinación de la actividad inmunomoduladora de dos extractos del hongo Grifola frondosa Dicks. Fr Gray, mediante ensayos in vitro / Termination of the immunomodulatory activity of two extracts of the fungus Grifola frondosa Dicks. Fr Gray, by in vitro tests

Fue evaluada la actividad de dos extractos del hongo comestible Grifola frondosa (Dicks; Fr) S.F. Gray, conocido comúnmente como maitake sobre el sistema inmune humano. Se estudió la actividad inmunomoduladora de los extractos acuoso y etanólico obtenidos del cuerpo fructífero del hongo sobre los linfocitos por medio de un ensayo linfoproliferativo y fueron realizados ensayos hematolíticos in vitro para probar su influencia sobre las vías clásicas y alterna del sistema de complemento. El ensayo de linfoproliferación fue realizado colocando linfocitos purificados expuestos a los extractos y cultivados para una evaluación final colorimétrica con XTT, una sal de tetrazolio que es reducida a un compuesto coloreado y soluble por la actividad enzimática mitocondrial presente en células vivas...

Production of Polysaccharide by the Edible Mushroom, Grifola frondosa

The production of polysaccharide according to various developmental stages (mycelium growth, primordium appearance, and fruiting-body formation) in the edible mushroom Grifola frondosa was studied. The cap of the mature mushroom showed the highest amount of polysacchride. Mycelial growth and polysaccharide synthesis were optimal at pH 5 and 20degrees C. Polysaccharide synthesis was maximal after 12 days of cultivation, whereas maximum mycelial growth was shown after 18 days. Mannose, cellobiose and starch increased the level of polysaccharide as well as growth in submerged culture. Glucose and sucrose appeared to be good substrates for fruiting of Grifola frondosa.

Effects of Grifola frondosa extracts on mouse immunity / 中国免疫学杂志

Objective :To investigate the effects of ethanol precipitate(ET-Pre) and RNA of Grifola frondosa on non-specific immunity in mouse.Methods:The common biological methods were used to examine the levels of cytokines and immunocyte activity. Results: The killing activity of the NK cells, the phagocytosis function of macrophages and the levels of TNF?/IL-1 in the animals treated with ET-Pre and RNA respectively were significantly higher than those in the control.The RNA was stronger than ET-Pre in increasing killing activity of NK cells and phagocytosis function of macrophages. Conclusion:Both ET-Pre and RNA extracts of Grifola frondosa may promote immunoactivity nonspecifi-cally and inhibit tumor cells indirectly.

STUDIES ON PRODUCTION OF EXPOLYSACCHARIDES OF GRIFOLA FRONDOSA IN SACCHARKID SOLUTION / 微生物学通报

Effects of glucose concentration and pH\|control upon production of exopolysaccharides of Grifola frondosa was studied.The results showed that glucose at concentration of 5% was favorable to exopolysaccharides production,and the pellets benefited from the controlled start pH as well as the controlled final pH of 3 5～4 0 to produce exopolysaccharides.Attempt on the exopolysaccharides production with recycled pellets in the saccharoid solution was also made in this work.

STUDIES ON THE TECHNOLOGICAL CONDITIONS FOR SUBMERGED CULTURE OFGRIFOLA FRONDOSA / 微生物学通报

The better conditions for flask fermentation of Grifola frondosa are:QF medium.25℃.pH4 5 filled volume 60mL/500mL flask.rotated speed 100rpm.When 0 4%CMC is added to medium,the growing point of mycelia can increase and the biomass is rised.Scale\|up test has done in 10 litre airlift bioreactor.The rate of biotransformation between biomass and original sugar or between biomass and consuming sugar is over 24% or up to 435%.In mycelium the polysaccharide content is 10 2%.In culture fluid the polysaccharide content is 1 38%.

EFFECTS OF CRUDE AND PURIFIED POLYSACCHARIDE FROM GRIFOLA FRONDOSA ON TUMOR GROWTH AND IMMUNEFUNCTION IN MICE / 营养学报

Objective:To compare the anti tumor activity and immune enhancing effect of crude(PGF) and purified (PGF 1) polysaccharide from Grifola frondosa. Methods:S 180 bearing mice were used as animal model. The effects on tumor weight and immune function were investigated. Results:PGF and PGF 1 showed inhibitory activity on S 180 growth. They could also increase weight of immune organs and improved the phagocytic function, DTH response, lymphocyte proliferation, antibody formation in splenic cells and content of serum HC IgM markedly. PGF was better than PGF 1. Conclusion:Both PGF and PGF 1 can inhibit S 180 tumor growth and enhance immune function in S 180 bearing mice.