International Journal of Medicinal Mushrooms

Published by Begell House
Print ISSN: 1521-9437
Beta-glucan is a major component of fungal cell walls and shows various immunopharmacological activities including antitumor activity. Previously, we detected anti-beta-glucan antibody in human sera. Anti-beta-glucan antibody participates in the immune response to fungal cell wall beta-glucan. Patients on dialysis are at high risk of infection including fungal infections. We examined the plasma beta-glucan level and the titer of anti-beta-glucan antibody in dialysis patients. We measured plasma beta-1,3-glucan concentrations with the limulus G test and anti-beta-glucan antibody titers by ELISA with Candida beta-glucan-coated plates. We also examined the influence of the period of dialysis and the kind of dialysis membrane. The patients were positive for beta-1,3-glucan in their plasma. The anti-beta-glucan antibody titer was lower in the dialysis patients than in healthy volunteers. Long-term dialysis patients showed lower anti-beta-glucan antibody titers than short-term dialysis patients. No significant difference was found between the kinds of dialysis membrane. The titer of anti-beta-glucan antibody as recognition molecule of beta-glucan was low in dialysis patients compared with healthy volunteers. This is likely to be one factor explaining the sensitivity to infection of the dialysis patients. An appropriate application of culinary-medicinal mushroom such as Agaricus brasiliensis has potential for the prevention of fungal infection in dialysis patients.
Response surface methodology was employed to optimize the concentration of four important cultivation media components such as cottonseed oil cake, glucose, NH4Cl, and MgSO4 for maximum medicinal polysaccharide yield by Lingzhi or Reishi medicinal mushroom, Ganoderma lucidum MTCC 1039 in submerged culture. The second-order polynomial model describing the relationship between media components and polysaccharide yield was fitted in coded units of the variables. The higher value of the coefficient of determination (R2 = 0.953) justified an excellent correlation between media components and polysaccharide yield, and the model fitted well with high statistical reliability and significance. The predicted optimum concentration of the media components was 3.0% cottonseed oil cake, 3.0% glucose, 0.15% NH4Cl, and 0.045% MgSO4, with the maximum predicted polysaccharide yield of 819.76 mg/L. The experimental polysaccharide yield at the predicted optimum media components was 854.29 mg/L, which was 4.22% higher than the predicted yield.
The influence of different carbon and nitrogen sources, pH of the culture medium, and temperature and period of cultivation on mycelial biomass production and protease activity by Lentinus citrinus DPUA 1535 were investigated in submerged culture. A 2(5) full factorial design with three central points was employed, and the results showed that at a significance level of 95% only nitrogen source and temperature were statistically significant for mycelial biomass production. On the other hand, for protease activity all factors and some interactions were significant, and the temperature and nitrogen source had the most significant effect. The best condition for mycelial biomass production (5.76 mg mL(-1)) and protease activity (32.3 U mL(-1)) was obtained in medium formulated with 0.5% soluble starch, 0.2% gelatin, pH 7.0, 25 degrees C, in 5 days.
Results of 60-Day Immune Assist 24/7™ Trial with 8 HIV+ Patients Without Antiretroviral Drug 
Immune enhancement through the use of natural products is a potentially valuable therapeutic modality in HIV-infected people, especially those who are not good candidates for aggressive ARV therapy. One such immune enhancement, a medicinal mushroom product from the United States, is Immune Assist 24/7. In this study the effect of Immune Assist 24/7, which is a naturally derived immune-modulating and antiviral agent, on CD4+ T-lymphocyte counts was evaluated in 8 HIV-infected patients at the Sunyani Regional Hospital (Ghana). The subjects were administered three tablets of 800 mg Immune Assist 24/7 once daily (2.4 g/day) and peripheral blood samples were drawn at baseline, day 30, and day 60, and the CD4+ count measured. The study revealed that Immune Assist 24/7, used as a sole therapeutic agent without additional ARV drugs, significantly increased CD4+ T-lymphocyte populations in all of the patients. In one patient, the CD4+ T-lymphocyte count went from 4 at the baseline, to 170 cells in 60 days, representing an increase of more than 4000%. In another patient, the CD4+ count went from 88 to 470 cells within the same period. Even in the patients with the highest CD4+ counts of around 800, there was a significant elevation in the CD4+ count noted. This study did not deal with the effect of Immune Assist 24/7 on other immune parameters such as CD3+ T-lymphocyte count, natural killer cells count, or viral load among HIV-infected patients. These initial results are promising, and indicate the potential value of further evaluating the effects of Immune Assist 24/7 on other immune parameters and viral load among HIV patients, administered either as a sole therapeutic agent, as an adjuvant with standard ARV therapy, or in comparison with standard ARV therapy alone.
A water-soluble polysaccharide named DI was extracted from the fruiting bodies of gastroid mushroom Dictyophora indusiata with boiling water. The chemical and physical characteristics of DI were investigated by a combination of chemical and instrumental analysis methods. The immunomodulatory activities on RAW 264.7 macrophage of DI in vitro were also studied. The results showed that DI is a β-(1→3)-glucan with side branches of β-(1→6)-glucosyl units, and it has triple-helical structure. DI has no toxic effect on cells, but can promote macrophage multiplication. DI significantly affects the immune function by promoting the production of nitric oxide and cytokines, such as tumor necrosis factor-α, interleukin-1, -6, and -12, showing an obvious dose-effect relationship. This work extends the application scope of the polysaccharide from D. indusiata in the biomedical field.
Turkey tail medicinal mushroom, Trametes versicolor (TV), is a species with a variety of pharmacological activities. Its intracellular polysaccharopeptides are widely commercialized. Recently, we found a novel TV strain LH-1 in Taiwan and demonstrated that the extracellular polysaccharopeptide (ePSP) of LH-1 obtained from submerged culture exhibits significant immunomodulatory activity. In this in vivo study, we further evaluated the safety of orally administered LH-1 ePSP using both male and female ICR mice. The LH-1 ePSP was orally administered to mice at levels of 0 (water), 100 (low dose), 500 (medium dose), or 1000 mg/kg/day (high dose) for 28 days. Clinical observations, growth, food consumption, histopathological examination, and clinical biochemical analyses revealed no adverse effects of LH-1 ePSP in mice. There were no significant differences in the results of target organ weights, hematological analyses, and urinalysis examination among groups. However, male mice that ingested high doses of LH-1 ePSP tended to have decreased lung weights and platelet numbers. In conclusion, the results of the present study suggested that oral administration of LH-1 ePSP for 28 days is accompanied by no obvious signs of toxicity. The lack of toxicity supports the potential use of LH-1 ePSP as a food or dietary supplement.
Spaceflight represents a complex environmental condition. Space mutagenesis breeding has achieved marked results over the years. The objective of this study is to determine the chemical changes in medicinal mushroom Ganoderma lucidum cultivated after spaceflight in 1999. Fourier transform infrared (FTIR) and two-dimensional infrared (2DIR) correlation spectroscopy were used in analysis. The sample Sx and its control Cx showed the least dissimilarities in one-dimensional FTIR spectra, but absorbance of Sx is twice as high as Cx. Sx presented a clear peak at 1648 cm in 2nd derivative spectra, which could not be detected in the Cx. The 2DIR spectra showed the intensity of Sx in the range 1800-1400 cm-1 for protein is higher than the control. The sample Sx produced some carbohydrate peaks in the area of 889 cm-1 compared with the Cx. The spaceflight set up an extreme condition and caused changes of chemical properties in G. lucidum strain.
The oxidative stability of sunflower oil supplemented with medicinal split gill mushroom, Schizophyllum commune's crude extract (CE), the formic acid (FA) fraction and semipurified subfractions (SF) II and IV were tested, compared to BHA and alpha-tocopherol, by measuring their peroxide value, iodine value, p-anisidine value, thiobarbituric acid-reactive substances, and free fatty acid content. Their total phenolic content (TPC), 2,2-diphenyl-1-picryhydrazyl (DPPH) radical scavenging, and ferric reducing/antioxidant power (FRAP) were also evaluated. FA and CE exhibited highest DPPH* scavenging, while FA and SFIV showed the highest FRAP; TPC was found to be highest in CE, FA, and SFIV. BHA and alpha-tocopherol are more protective in stabilizing the sunflower oil; SFII and SFIV had short-term protective effect in secondary oxidation for 1 year, while CE and FA retarded secondary oxidation and extended the shelf life 1 1/2 years and 2 years, respectively. HPLC-DAD analysis found (+)-catechin in Sch. commune's extracts. Sch. commune's extracts did not show similar retardation of lipid oxidation in sunflower oil as compared to alpha-tocopherol and BHA at the 200 ppm level. However, the higher concentration of Sch. commune's extract that provided the protective effect in stabilizing sunflower oil can be further studied.
This study was conducted to evaluate the effects of topical application of aqueous extract of Hericium erinaceus fruiting bodies (HEFB) on the rate of wound healing enclosure and histology of the healed wound. Five groups of male Sprague-Dawley rats were experimentally wounded in the posterior neck area. A uniform wound area of 2.00 cm in diameter, using a circular stamp, was excised from the nape of the dorsal neck of all rats with the aid of a round seal. The animal groups were topically treated, respectively, with 0.2 mL each of sterilized distilled water (sdH2O); Intrasite gel; and 20, 30, and 40 mg/mL HEFB. Macroscopically, those rats whose wounds were dressed with HEFB and those in the Intrasite gel-treated group healed earlier than those treated with sdH2O. Histological analysis of healed wounds dressed with HEFB showed less scar width at wound enclosure and the healed wound contained fewer macrophages and more collagen with angiogenesis, compared to wounds dressed with sdH2O. In conclusion, wounds dressed with HEFB significantly enhanced the acceleration of wound healing enclosure in rats.
Pancreatic cancer, one of the deadliest of all solid malignancies, is one of the leading causes of cancer death worldwide, with 232,000 new cases and 213,000 deaths reported each year. These unfortunate statistics reflect the advanced stage at which most patients with pancreatic cancer are diagnosed and the paucity of effective chemotherapeutic regimens. Fungal metabolites have been gaining scientific interest because of their medicinal properties. In the present study, 31 different mushroom extracts of 12 medicinal mushroom species were screened for their effect on the viability of human pancreatic adenocarcinoma cells. Extraction procedures were executed with organic solvents--ethanol (EAL), ethyl acetate (EAC), and chloroform (CHL). In some cases, culture liquid (CL) extraction was also performed. All extracts were diluted to a concentration of 50 mg/mL dimethyl sulfoxide. Extract effects on cell viability were examined in human pancreatic adenocarcinoma cells HPAF-II (well differentiated) and PL5 (porrly differentiated), using XTT assay and crystal violet assay (CV). Furthermore, extract effects on LDH leakage were also studied in order to exclude necrotic damage of the extract. The screening phase revealed that among the total 31 extracts examined with various treatment doses (50-500 μg/mL) administered for 72 h, the CL extract of the mushroom Cyathus striatus exhibited the most prominent decrease in cell viability. Moreover, exposure of cells to lower concentrations then the above (1, 2.5, 5, 7.5, 10, 15, 20, and 50 μg/mL) for 24, 48, and 72 h showed a significant decrease in cell viability. Crystal violet results support these findings, and LDH levels measured suggest the lack of a necrotic effect of the extract. Our results indicate that C. striatus CL extract inhibits the viability of human pancreatic adenocarcinoma cells; HPAF-II and PL45. Growth inhibition can be achieved in low concentrations of the extract and a short exposure period. This effect can be mediated through apoptosis induction and/or cell cycle arrest; therefore, additional experiments are needed in order to elucidate the extract mechanism of action. These findings may lead to the development of new therapeutic strategies for the treatment of pancreatic cancer.
Beta-glucan (BG) is a representative pathogen-associated molecular pattern (PAMP) produced by pathogenic fungi. SCG is a BG obtained from Sparassis crispa, which stimulates splenocytes in DBA/2 mice to produce cytokines, such as GM-CSF, IFN-γ, and TNF-α. In the present study, we analyzed the molecular mechanism of SCG-mediated cytokine synthesis using cytocharasin D (CytD), an inhibitor of actin polymerization. It was found that GM-CSF and TNF-α synthesis of splenocytes stimulated with SCG, but not with lipopolysaccharide, was significantly enhanced in the presence of CytD. CRDO, partially hydrolyzed linear 1,3-BG curdlan, stimulated splenocytes of DBA/2 mice slightly to produce cytokines. CRDO, acting as an antagonist in the presence of SCG, changed to a strong agonist in the presence of CytD. CytD also enhanced cytokine synthesis of bone marrow-derived dendritic cells. Taken together, cytokine productivity of BG was significantly dependent on molecular weight, and CytD treatment is useful to enhance the sensitivity for analyzing the immunostimulating activity of BG in vitro.
In our previous research, Cordyceps militaris (CM) had a hypoglycemic effect in normal rats. In this study we wanted to elucidate whether CM also had an effect on diabetic rats. Twelve rats with streptozotocin-induced diabetes were separated randomly into 2 groups. First, aqueous extracts of CM 10 mg/kg (CM group) or saline (control group) was fed to the rats; then the plasma glucose levels were assayed. Second, the signaling proteins IRS-1 and GLUT-4 collected from the muscle were detected. Finally, another 2 groups of rats were injected with atropine 0.1 mg/kg intraperitoneally just before the CM/saline feeding, and the assays mentioned above were repeated. Blood glucose decreased 7.2% in the CM group but only 1.5% in the control group (P < 0.05). The IRS-1 signal was 2.9-fold higher than actin in the CM group but only 0.8-fold higher in the control group (P < 0.005). In GLUT-4 signal, the difference was 1.7- vs. 0.6-fold, respectively, compared with actin (P < 0.05). However, atropine injection made CM-induced hypoglycemia or elevation of IRS-1 and GLUT-4 not significant. In conclusion, CM had a hypoglycemic effect in diabetic rats and atropine blocked it. Therefore, the cholinergic activation also was considered to be involved in the hypoglycemic effect of CM in rats with streptozotocin-induced diabetes.
Agaricus brasiliensis has been demonstrated to have potent antitumor activity. The activity is postulated to act through mediation of the host immune system. We have reported that A. brasiliensis extract (ABE) inhibited compound 48/80 induced a systemic anaphylaxis-like reaction, ear swelling response, and passive cutaneous anaphylaxis-like reaction in mice. There is some recent information available on the mechanism of antiallergic effects resulting from oral administration of ABE. However, information regarding how ABE may activate macrophages through intestinal epithelial cells is still limited. To clarify the mechanism of macrophages activation by ABE, a gut in vitro model constructed of Caco-2 and RAW264.7 cells was applied. Treatment of ABE to the apical compartment resulted in significant increases in tumor necrosis factor (TNF)-α production in the basolateral compartment. Moreover, addition of catalase to the basolateral compartment before ABE treatment suppressed TNF-α production completely, but the addition of superoxide dismutase did not suppress this at all. These data suggest that ABE could potentiate hydrogen peroxide emissions from Caco-2 cells into the basolateral side and activate macrophages, which is important in the immune system.
Armillaridin (AM) is an aromatic ester compound isolated from honey medicinal mushroom, Armillaria mellea, which has anti-cancer potential. This study was designed to examine the effects of AM on differentiation and activation macrophages, the major ontogeny of innate immunity. Macrophages were derived from CD14+ monocytes which were sorted from human peripheral blood mononuclear cells. Cell viability was assessed by trypan blue exclusion test. Cells were stained with Liu's dye for observation of morphology. Expression of surface antigens was examined by flow cytometric analysis. Phagocytosis and generation of reactive oxygen species (ROS), as functional assays, were evaluated by counting engulfed yeasts and DCFH-DA reaction. The viability of macrophages was not significantly reduced by AM. AM at nontoxic concentrations markedly increased cytoplasmic vacuoles. The expression of surface CD14, CD16, CD36, and HLA-DR was suppressed. The phagocytosis function, but not ROS production, of macrophages was inhibited by AM. Armillaridin could inhibit the differentiation and activation of human macrophages. It may have potential to be developed as a biological response modifier for inflammatory diseases.
Ethanolic extracts of fruit bodies of 5 species (8 strains) of the genus Phellinus, and isolated fractions derived from 1 of these extracts (Ph. baumii PB-10), were evaluated for antioxidant activity, inhibitory effects on the growth of human tumor cells, and the capacity to protect PC12 cells against H2O2-induced oxidative damage. Extracts of all 8 strains of Phellinus spp. exhibited antioxidant activity and protected PC12 cells against oxidative damage at different magnitudes of potency. The strongest antioxidant activity was exhibited by extracts of Ph. baumii PB-10, with recorded IC50 values for superoxide radical and hydrogen peroxide scavenging activity of 3.76 microg/mL and 4.24 microg/mL, respectively. Radical-scavenging activity and protection levels against H2O2-induced damage to PC12 cells were highly correlated with the flavonoid content of the extracts and isolated fractions. All the extracts inhibited L1210, SW620, and MCF-7 tumor cell proliferation at 200 microg/mL concentrations, but inhibition was not correlated with the flavone content of the test samples and was clearly dependent upon the presence of other, as yet, unidentified components. Our data indicate that fruit bodies of species of the genus Phellinus represent a potentially valuable source of natural antioxidants of relevance to both the health and food industries.
α-Glycosidase inhibitory effect of positive control (acarbose) (A) and Ganoderma lucidum (B). 
Dose-dependent aldose reductase inhibitory activity of Ganoderma lucidum.
Total Phenolic Content, Total Flavonoid, and DPPH Free Radical Scavenging Activities of Mushrooms
The objective of the current study was to verify antidiabetic effects of different types of mushrooms as folk medicines in treating diabetes. The antidiabetic effects were evaluated by in vitro α-glycosidase and aldose reductase (AR) inhibitory assays and antioxidant activity assay. Ganoderma lucidum extract exhibited the best dose-dependent inhibitory activity against α-glycosidase with IC50 at 4.88 mg/mL, and also exhibited aldose reductase inhibitory potential with IC50 value of 9.87 mg/mL. Tremella fuciformis demonstrated the highest AR inhibitory activity (IC50=8.39 mg/mL). Antioxidant activities of selected mushrooms were evaluated based on the total phenolic content (TPC), total flavonoids content (TFC), and DPPH free radical scavenging activity. The result showed that G. lucidum contained the highest TPC (39.3 mg GAE/g sample extract), TFC (15.1 mg CE/g sample extract), and the strongest DPPH free radical scavenging activity (IC50=3.66 mg/mL) among the mushroom samples.
Schematic diagram for the process of exopolysaccharide (EXP) and endopolysaccharide (ENP) fractions from submerged mycelial cultures of mushrooms. DIW, deionized water; EtOH, ethanol. 
Proportional relation (percentage) of flavonoid content to phenolic content in submerged mycelia cultures of mushrooms. A: Exopolysaccharide. B: Endopolysaccharide.
Influence of exopolysaccharide fractions from submerged cultures of mycelia on cytokine production by activated human T lymphocytes. Data shown are mean ± standard deviation and expressed as a percentage of phytohemaglutinin (PHA) control. A: interferon (IFN)-γ; B: interleukin (IL)-2; C: IL-4; D: IL-5. M1, Pleurotus citrinopileatus; M2, P. australis; M3, P. pulmonarius; M4, Tremella mesenterica; M5, Cryptoporus volvatus; M6, Cordyceps militaris; M7, C. sinensis; UT, untreated. *Significant difference from control (PHA-treated group) (n = 3), P < 0.05.
Effects of exopolysaccharide fractions from submerged cultures of mycelia on the cellular lysosomal enzyme activity of mouse peritoneal macrophages. A: Exopolysaccharide. B: Endopolysaccharide. Data shown are mean ± standard deviation and expressed as a percentage of saline. Macrophage concentration was 1 × 10 6 cells/ mL. LPS, lipopolysaccharide (positive control; from Escherichia coli 0127: B8); M1, Pleurotus citrinopileatus ; M2, P. australis ; M3, P. pulmonarius ; M4, Tremella mesenterica ; M5, Cryptoporus volvatus ; M6, Cordyceps militaris ; M7, C. sinensis 
Correlation between flavonoid content exopolysaccharide (EXP) and endopolysaccharide (ENP) fractions ( A ) and ferrous ion-chelating capacity of EXP and ENP fractions ( B ). 
A number of mushrooms are known to possess pharmacological activities. In this study, the phenolic and flavonoid contents of extracts of exo- and endopolysaccharide fractions obtained from submerged mycelia cultures of 7 edible or medicinal mushroom species, as well as their antioxidant and immunomodulatory properties, were evaluated. The exo- and endopolysaccharide yields were 0.576-1.950 and 0.438-0.933 g/L, respectively. The sugar and protein contents of these fractions were analyzed and contained predominantly sugars (52.3-87.6%). The exo- and endopolysaccharide fractions contained appreciable amounts of phenolics and flavonoids. The highest flavonoid contents were found in Cryptosporus volvatus (349.6 mg/g), followed by Cordyceps militaris (312.6 mg/g). The antioxidant activities were evaluated by 4 assays: biological assay using Saccharomyces cerevisiae, DPPH radical scavenging activity, chelating ability for ferrous ions and ferric reducing antioxidant power. The mycelia polysaccharide fractions had more ferric reducing antioxidant power than other antioxidant activities. Both exo- and endo polysaccharides of C. volvatus inhibited production of the T lymphocyte Th1 cytokines interferon (IFN)-γ and interleukin (IL)-2, the Th2 cytokines IL-4 and IL-5, and macrophage enzyme activity. Although those from C. militaris had similar inhibitory effects on cytokine production, the exopolysaccharides stimulated macrophage enzyme activity. The other exopolysaccharides (Pleurotus citrinopileatus, P. australis, and P. pulmonarius) inhibited IFN-γ and IL-5 production, but they had varying effects on IL-2 and IL-4 production. Only 3 exopolysaccharides (P. pulmonarius, Tremella mesenterica, and Cordyceps sinensis) also stimulated macrophage enzyme activity to the same extent as lipopolysaccharides. All of them reduced IL-5 production, but those from T. mesenterica also inhibited IFN-γ, IL-2, and IL-4 production. Thus the polysaccharide fractions from the mushrooms studied have antioxidant activities and general immunomodulating effects in vitro.
The entomopathogenic fungus Cod-MK1201 was isolated from a dead cicada nymph. Three regions of ribosomal nuclear DNA, the internal transcribed spacers of nuclear ribosomal DNA repeats (ITS), the partial small subunit of rDNA (nrSSU) , and the partial large subunit of rDNA (nrLSU), and two protein-coding regions, the elongation factor 1α (EF-1α), and the largest subunit of the RNA polymerase II (rpb1) gene, were sequenced and used for fungal identification. The phylogenetic analysis of the ITS and the combined data set of the five genes indicated that the fungal isolate Cod-MK1201 is a new strain of Cordyceps sp. that is closely related to Cordyceps nipponica and C. kanzashiana. Crude extracts of mycelium-cultured Cod-MK1201 were obtained using distilled water and 50% (v/v) ethanol, and the antibacterial activity of each was determined. Both extracts had activity against Gram-positive and Gram-negative bacteria, but the ethanol extract was the more potent of the two. The antibacterial activity of the protein fractions of these extracts was also determined. The protein fraction from the ethanol extract was more antibacterial than the protein fraction from the aqueous extract. Three antibacterial constituents including adenosine, the total phenolic content (TPC), and the total flavonoid content (TFC) was also determined. The results showed that the adenosine content, the TPC, and the TFC of the ethanol extract were more active than those of the aqueous extract. Moreover, synergism was detected between these antibacterial constituents. In conclusion, the entomopathogenic fungal isolate Cod-MK1201 represents a natural source of antibacterial agents.
Antrodia camphorata is an extremely rare fungus native to the forested regions of Taiwan. It is also a traditional Chinese medicine, and Taiwanese aborigines applied it for treating liver diseases and protecting from food and drug intoxication. Scientific studies have demonstrated that A. camphorata crude extracts and pure compounds possess a variety of beneficial functions, such as anti-hypertensive, anti-hyperlipidemic, anti-inflammatory, anti-oxidant, anti-tumor, and immuno-modulatory activities. Recent studies have shown that many of these biological and pharmacological activities can be attributed to various active constituents, including polysaccharides, terpenoids, steroids, lignans, benzoquinone derivatives, benzenoids, and maleic and succinic acid derivatives. A. camphorata has been considered as a novel phytotherapeutic agent. However, detailed mechanistic studies or even clinical trials on A. camphorata are still rare. With the help of modern analytical techniques, it is not surprising that many novel constituents are being identified or fractionated from A. camphorata mycelium and fruiting bodies. This review summarizes the latest published results from A. camphorata research, focusing on the biological and pharmacological activities of the crude extract and known constituents of A. camphorata.
To obtain a low-molecular-weight polysaccharide with immuno-enhancing activity, hot water extract of Ganoderma lucidum fruit bodies was separated by membrane ultrafiltration, anion exchange, and gel filtration chromatography, and the immunological activities of fractions were assessed on the basis of nitric oxide production by RAW 264.7 macrophages. A novel polysaccharide (TB3-2-2) was successfully isolated and purified. TB3-2-2 is a homogeneous polysaccharide, with a relative molecular weight of 5.11 × 103 Da, identified by high-performance liquid chromatography and was composed of galactose and glucose in a molar ratio of 2:3 determined by high-performance anion exchange chromatography. TB3-2-2 had a carbohydrate content of 99%, as measured using the phenol-sulfuric acid method. Proliferation of mouse spleen lymphocytes and the expression level of interleukin-6 was significantly increased by TB3-2-2. Results indicate that the low-molecular-weight polysaccharide with immunological activity in G. lucidum is worthy of further research and development.
FT-IR spectra of the Xylaria nigripes poly- saccharides from the bottle were XnFB-1, XnFB-2, XnIPS-1, XnIPS-2, XnEPS-1, and XnEPS-2, respec- tively, which were obtained from the fruiting body and mycelium. FT-IR assignments, wave number (cm –1 ): 3400–3500 shows hydroxyl groups’ stretching vibration, 2919 shows characteristic absorption of the C-H bond stretching vibration, 1057 was due to the pyranose ring, 890 was assigned to the β-glycosidic linkage, and a band at 920 was attributable to the α-linkage. 
Chelating ferrous ion ability of XnFB-1, XnFB-2, XnIPS-1, XnIPS-2, XnEPS-1, and XnEPS-2. 
ABTS radical scavenging activity of XnFB-1, XnFB-2, XnIPS-1, XnIPS-2, XnEPS-1, and XnEPS-2. 
DPPH radical scavenging activity of XnFB-1, XnFB-2, XnIPS-1, XnIPS-2, XnEPS-1, and XnEPS-2. 
Xylaria nigripes, a local rare medicinal fungus, has multi-antioxidant activities owing to its water extraction as shown by previous research. However, the main indicator causing the antioxidant effect was not clear, so this research focused on the antioxidant activities from different sources of X. nigripes such as fruiting body polysaccharides, mycelium intracellular polysaccharides, mycelium extracellular polysaccharides, and their deproteinization products. The mycelium intracellular polysaccharide (XnIPS-1) from X. nigripes showed the highest reducing power of antioxidant activity, since it revealed the lowest IC50 values in all the assayed methodologies. The IC50 values of chelating ferrous ion ability, ABTS radical scavenging activity, and DPPH free radical scavenging were 1412, 174.25, and 351.56 µg/mL, respectively. In addition to these results, this research also explored the mechanism between polysaccharides and antioxidants compared by FT-IR analysis. The spectrum shows that the X. nigripes polysaccharide structure changed after the proteins were removed.
The immunomodulatory activities of different solvent extracts from the culinary-medicinal mushroom Tricholoma matsutake were studied in vivo in normal mice. The extracts were prepared using different solvents in an order of increasing polarity. The immunomodulatory activities were investigated by measuring the thymus and spleen index, phagocytic rate of macrophage phagocytosis, delayed-type hypersensitivity, plaque-forming cell, and proliferation of splenocytes. Results demonstrated that water extract (WE) and n-butyl alcohol extract (BAE) of T. matsutake could enhance the immunity of mice significantly compared with the control group. Main components of WE and BAE were polysaccharides, proteins, and flavonoids; we presume that these may be the main immunomodulating and immuno-enhancing agents in T. matsutake.
The present study aims to assess the antioxidant activities (AOA) and total phenolic content (TPC) of water extracts of selected edible wild mushrooms: Pleurotus porrigens, Schizophyllum commune, Hygrocybe conica, and Lentinus ciliatus. The AOA were evaluated against DPPH radical and ABTS radical cation scavenging ability, ferric-reducing antioxidant power (FRAP) and beta-carotene-linoleate bleaching (beta-CB) assays, and the Folin-Ciocalteu method for TPC. BHA was used as reference. P. porrigens showed significantly higher (p < 0.05) DPPH* scavenging ability (90.78 +/- 0.30%) and FRAP (6.37 +/- 0.22 mM FE/100g), while Sch. commune showed significantly higher (p < 0.05) ABTS*+ inhibition activity (94.96 +/- 0.70%) and beta-CB inhibition activity (94.18 +/- 0.17%), respectively. TPC was found in a descending order of P. poriggens > L. ciliatus = Pleurotus ostreatus (cultivated) > H. conica = Sch. commune. Positive correlation was observed between the AOA and TPC. When compared to BHA (2 mM), P. porrigens showed significantly higher (p < 0.05) DPPH* scavenging ability and reducing power, while Sch. commune showed comparable DPPH* scavenging ability and ABTS*+ inhibition activity. All the mushrooms have better ABTS*+ inhibition activity than BHA (1 mM). The beta-CB inhibition activity of BHA was significantly higher than those of edible wild mushrooms. The water extracts of edible wild mushrooms showed potent antioxidant activities compared to BHA to a certain extent.
TNF-α secretion in PBMC. Human PBMC (1 x 10 6 cells/mL) were treated with 12.5, 100, and 200 µg/mL of Grifola frondosa extract. The numbers represent the extracts from corresponding fruiting bodies obtained from different substrates.
IFN-γ secretion in PBMC. Human PBMC (1 x 10 6 cells/mL) were treated with 12.5, 100, and 200 ug/mL of Grofola frondosa extract. IFN-γ values for 12.5 and 100 µg/mL treatments are not shown because they were below the detection limit. The numbers represent the extracts from corresponding fruiting bodies obtained from different substrates.
Grifola frondosa is a culinary-medicinal mushroom that contains several physiologically active compounds, of which polysaccharides, specifically β-glucans, are known to possess immunomodulating properties. Its extracts are studied for application as adjuncts for chemotherapy, and experiments in animal models support the use of this mushroom for cancer treatment. The effect of extracts obtained from mushrooms cultivated on different substrates and their capacity of inducing the secretion of cytokines from human peripheral blood mononuclear cells were studied. The activity of extracts at concentrations 12.5, 100, and 200 μg/mL on induction of TNF-α, IFN-γ, and IL-12 was screened. Two extracts from substrates fortified with olive oil press cakes showed appreciable activity and induced the secretion of TNF-α, IL-12, and INF-γ. The extracts differed from the others in the amount of sugar, protein, and β-glucans, which can explain their higher activity. Present results show that different substrates and different source materials can reasonably modify the bioactivity of cultivated G. frondosa.
Effect of hot-water and ethanolic extracts from Taiwanofungus salmoneus on lipopolysaccharide (LPS)- induced nitric oxide production in RAW 264.7 cells. Each value is expressed as mean ± standard error (n = 3). Means with same letter within an extract are not significantly different ( P > 0.05). 
The Inhibition Zone of Hot-Water and Ethanolic Extracts from Taiwanofungus salmoneus Mycelia Against Various Pathogenic Bacteria Using the Hole-Plate Diffusion Method
Effect of hot-water and ethanolic extracts from Taiwanofungus salmoneus on lipopolysaccharide (LPS)- induced tumor necrosis factor (TNF)- α production in RAW 264.7 cells. Each value is expressed as mean ± standard error (n = 3). Means with different letters within an extract are significantly different ( P < 0.05). 
Taiwanofungus salmoneus (T.T. Chang et W.N. Chou) Sheng H. Wu et al. (shiang-shan-chih), is a medicinal fungus indigenous to Taiwan. The mycelium was prepared from submerged culture and its ethanolic and hot-water extracts were used to study its antibacterial and anti-inflammatory activities. Gram-positive species (Bacillus cereus, Listeria monocytogenes, and Staphylococcus aureus) and gram-negative species (Escherichia coli and Salmonella typhimurium) of bacteria were used. In addition to the inhibitory zone, minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs) also were determined. The ethanolic extracts showed higher inhibitory and bactericidal activities (MIC and MBC: 6.25-12.50 mg/ml) than the hot-water extracts (MIC and MBC: 25-50 mg/mL). In the anti-inflammatory test, the extracts were tested on lipopolysaccharide-induced nitric oxide and tumor necrosis factor- α production in RAW 264.7 cells. The values of the inhibition concentration at 50% of nitric oxide production were 18.2 and 14.2 μg/mL for the hot-water and ethanolic extracts, respectively. The 50% inhibitory concentration values of tumor necrosis factor- α production were 4.99 and 7.13 μg/mL for the hot-water and ethanolic extracts, respectively. On the basis of the results obtained, the mycelia could be used as an antibacterial and anti-inflammatory supplement.
The aim of this study is to evaluate the in vitro effects of aqueous extracts of three species of Algerian desert truffles (Terfezia claveryi, T. leonis, and Tirmania nivea) on the growth of Pseudomonas aeruginosa and Staphylococcus aureus. The antimicrobial activity of the three aqueous extracts was tested using the agar well diffusion and kinetic bacterial growth curves methods. The aqueous extracts of Terfezia claveryi and Tirmania nivea were found to possess a very powerful antibacterial activity against both S. aureus and P. aeruginosa using agar well diffusion. Using 4% and 11% of the aqueous extracts of T. claveryi and T. nivea in the growth medium of S. aureus caused a significant inhibition of S. aureus growth by 86.48% and 99.09%, respectively. The aqueous extracts of T. claveryi and T. nivea were found to cause a significant inhibition of the growth of P. aeruginosa by 71.11% and 100%, respectively. However, the aqueous extract of Terfecia leonis did not show any antibacterial activity. Therefore, T. claveryi and Tirmania nivea can be considered a source of natural therapeutic agents that can be used to treat eye infections caused by resistant bacteria such as P. aeruginosa and S. aureus.
Ethanolic extracts of three wild medicinal mushrooms, namely Lenzites betulina (LET), Trametes versicolor (TET), and Coriolopsis polyzona (CET), collected from Akure, southwest Nigeria, were assessed for their lipid peroxidation, anti-inflammatory, and acute toxicity effects. The inhibition of the formation of thiobarbituric acid reactive species (TBARS) by extracts was concentration dependent and ranged from 86.99% to 92.18% at 1000 µg/ mL. The IC50 of the extracts was also in the range of 222.81 µg/mL to 737.13 µg/mL. The anti-inflammatory effect measured by inhibition of mice ear edema was higher and significantly different (P ≤ 0.05) than the control. The acute toxicity test also revealed tolerance to the three ethanolic extracts by Artemia salina at concentrations of 10 µg/mL to 1000 µg/mL, except for ethanolic extracts of LET and TET, which exhibited toxicity against this invertebrate at 1000 µg/mL. This research has shown that ethanolic extracts of these three macrofungi could be good sources of safe and effective antioxidant and antinflammatory agents for biopharmaceutical exploitation.
In general, Cordyceps sinensis is much more popular than C. militaris, though both species contain quite similar bioactive ingredients and exhibit medicinal activities. Many bioactive ingredients have been isolated from C. militaris, such as adenosine, cordycepin, D-mannitol, and exopolysaccharides. C. militaris is claimed to have extensive pharmacological properties, such as: anti-inflammatory; anti-fatigue; anti-bacterial; anti-diabetic; improve lung, liver, and kidney functions; to be beneficial for treating cancer as well as male and female sexual dysfunctions. C. militaris is fast gaining momentum for its so-called health benefits, and it is often used as a substitute for C. sinensis. In view of the growing popularity of C. militaris, nowadays C. militaris cultivation for stroma is also done. There is a great diversity of compounds from different strains of Cordyceps and different artificially cultivated products. This study is to determine the optimum culture parameters integrated with substrate of choice to bring the indoor-cultivated C. militaris to a higher and more consistent level of quality. To achieve the above objective, the resultant products after growth were analyzed for adenosine, cordycepin, and D-mannitol using the high-performance liquid chromatography method. The optimum culture condition to produce a high level of adenosine is by using millet as solid substrate. It must be cultivated in the dark for the first 7 days and harvested on day 40. The optimum culture condition to produce a high level of cordycepin is by using soybean as solid substrate. It must be cultivated in the dark for the first 14 days and harvested on day 50. While a high level of D-mannitol is achieved with millet as the solid substrate. It must be kept in the dark for the first 7 days and harvested on day 50. The adenosine level decreased and cordycepin increased from day 40 of culture to day 50 generally.
Pholiota adiposa is a mushroom with excellent medicinal and nutritional properties. After culture in fermentation medium, Ph. Adiposa mycelia were filtered, lyophilized, and powdered. A crude polysaccharide (PAP) of Ph. Adiposa was prepared from the mycelial powder with hot water, centrifuged, and the resulting supernatant lyophilized. PAP was fractionated by 30%, 60%, and 80% ethanol precipitation steps to yield PAP30, PAP60, and PAP80. Subsequently PAP30-1 and PAP30-2, PAP60-1 and PAP60-2, and PAP80-1 and PAP80-2 were isolated from PAP30, PAP60, and PAP80, respectively, by ion-exchange chromatography on a DEAE-Sepharose column. Polysaccharide content increased from 43.8% in PAP to 50.54%~73.19% in PAP30-1~PAP80-2. The protein content was 4.92% at minimum in these polysaccharide products. In order to identify the chemical composition, the six polysaccharides (PAP30-1, PAP30-2, PAP60-1, PAP60-2, PAP80-1, and PAP80-2) were further purified by gel filtration on Sephacryl S-100-500. Finally, three water-soluble polysaccharides (PAP30-2a, PAP60-2b, and PAP80-2a) were obtained. HPLC analysis revealed that PAP30-2a, PAP60-2b, and PAP80-2a exhibited a molecular weight of 6.6 × 105 Da, 8.4 × 103 Da, and 3.5 × 103 Da, respectively. The glucose content in PAP80-2a, PAP60-2b, and PAP30-2a was 57.8%, 72.7%, and 68.9%, respectively. PAP30-2a, PAP60-2b, and PAP80-2a demonstrated significant differences in anti-tumor activity in mice. PAP80-2a is the optimal bioactive constituent with anti-tumor and T-lymphocyte proliferation stimulating effects.
In the present investigation 16 species of Phellinus and 6 species of Hymenochaete (collected as an adulterant) were screened for sesquiterpenoids and triterpenoids. A total of 11 spots were detected in both sesquiterpenoids and triterpenoids chromatograms. The terpenoids were not identified. The spots obtained for Phellinus were compared with the spots of Hymenochaete. It was revealed from the SAB and D values that almost half of the species of Phellinus have about 45% to 57% dissimilarity in case of sesquiterpenoids and 50% to 60% dissimilarity with the triterpenoids. However, since both the taxa are from the same family, the spots that were common may be characteristic of the family. Such a study may be used to reveal the adulteration in medicinal Phellinus samples.
There is a growing need for new and effective antibiotic agents due to the recent emergence of life-threatening, multidrug-resistant bacterial infections such as methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa. In the present study, the antimicrobial potential of mushroom was investigated against multidrug-resistant bacterial strains. The mushroom was identified as Xylaria sp. strain R005 based on the morphological characteristics and confirmed by 18S ribosomal RNA sequence comparisons. The crude ethyl acetate extracts of culture filtrate and fruiting bodies of Xylaria sp. showed significant antibacterial activity against multidrug-resistant S. aureus strains (1-10) and P. aeruginosa strains (1-8). The minimum inhibitory concentration of the ethyl acetate extracts of culture filtrate and fruiting bodies ranged from 225 µg/mL to 625 µg/mL, and 120 µg/mL to 625 µg/mL, respectively, against clinical strains of S. aurues and P. aeruginosa. The synergistic action of extracts of Xylaria sp. with vancomycin and ciprofloxacin was observed against S. aureus strain 6 and P. aeruginosa strain 3, respectively. The fractional inhibitory concentration indices (FICIs) of culture filtrate extract with vancomycin and ciprofloxacin were 0.5 and 0.18, respectively. The FICI of fruiting body extract with vancomycin and ciprofloxacin were 0.5 and 0.375, respectively. These results clearly indicate that the metabolites of culture filtrate and fruiting bodies of Xylaria sp. are the potential source for production of new antimicrobial compounds.
Antifungal activity of methanolic extracts from Phellinus spp. against Alternaria alternata. Different letters among bars indicate significant differences among means (P < 0.05). 
phenolics, flavonoids and antioxidant capacity of methanolic extracts from Phellinus spp. 
The main objective of this study was to evaluate the antioxidant capacity of methanolic extracts from species of genus Phellinus: Ph. fastuosus, Ph. grenadensis, Ph. Merrillii, and Ph. Badius, in their respective polar fractions (aqueous) and nonpolar extracts (ethyl acetate), through tests of free-radical inactivation and hemolysis inhibition. The fungus species that gave the extract with the highest phenol content, total flavonoids, and antioxidant capacity [DPPH·, Trolox equivalents antioxidant capacity (TEAC), and hemolysis inhibition] was Ph. Merrillii, followed by Ph. fastuosus, Ph. Grenadensis, and Ph. Badius. The antioxidant capacities of the extracts, in descending order, were as follows: Ph. Merrillii (nonpolar), Ph. Fastuosus (nonpolar), Ph. Grenadensis (nonpolar), Ph. Fastuosus (polar), Ph. Merrillii (polar), Ph. Grenadensis (polar), Ph. Badius (nonpolar), and Ph. Badius (polar). Antioxidant capacity in the above Phellinus fungi species had EC50 values for DPPH inhibition of 0.45, 0.88, 1.31, 1.89, 2.14, 2.22, 3.42, and 6.00 mg/mL, respectively; TEAC values of 10400.29, 7635.53, 4855.05, 4415.39, 4041.68, 2989.2, 1937.7, and 842.42 µmol TE/g, respectively; and hemolysis inhibition values of 72.83, 66.95, 50.87, 50.28, 48.5, 42.82, 42.37, and 37.91%, respectively. In general, the fungus extract with the highest antioxidant capacity was the nonpolar fraction of Ph. Merrillii. The Phellinus species studied represent potential natural sources of bioactive compounds with antioxidant activity.
Inhabitants of the Mount Cameroon region depend on the forest resources of the region for their livelihood, including the diverse use of macrofungi. With the increasing loss of forest due to exploitation and urbanization, they are liable to rapidly lose their indigenous knowledge of the forest resources, especially of mushrooms. An ethnomycological survey was conducted with the aim of documenting the indigenous knowledge of mushrooms as a prelude to conservation efforts. We also sought to assess the mycophilic and mycophobic tendencies of the inhabitants. It was revealed that traditionally, mushrooms were used as food, medicine, for mythological purposes, for aesthetics, and some poisonous species were also recorded. At least 15 different species were identified to be edible among the Bakweri people. Species used for ethnomedicine among the Bakweris belonged to several genera, including Termitomyces, Auricularia, Agaricus, Daldinia, Dictyophora, Pleurotus, Russula, Trametes, Chlorophyllum, and Ganoderma. Mushrooms were used as love charms, for dispelling evil spirits, and as part of cultural festivals.
The agaricoglyceride is a new fungal secondary metabolite that constitutes esters of chlorinated 4-hydroxy benzoic acid and glycerol. The objective of this study was to explore whether the administration of agaricoglyceride could correct hepatic glycemic metabolism dysfunction by attenuating inflammation in the liver. The effects of agaricoglycerides on tumor necrosis factor-α, interleukin-1β, vascular endothelial growth factor-α, interleukin-17, insulin secretion, adiponectin, leptin, hepatic glycogen, nuclear factor-κB activation, and total antioxidant activity were studied respectively. We demonstrated that administration of agaricoglycerides alleviated glycemic metabolism dysfunction, inflammation, and oxidative stress in mice. These data indicate that agaricoglyceride supplementation could restrain metabolic dysfunction through suppressing the nuclear factor-κB pathway as well as decreasing the levels of inflammatory cytokines and total antioxidant activities.
Cultivation of the culinary-medicinal Lung Oyster mushroom, Pleurotus pulmonarius, on the stalks of three grass plants, i.e., Panicum repens, Pennisetum purpureum, and Zea mays were investigated. The effects of various combinatorial substrates on mushroom mycelial growth and yield calculated as biological efficiency (BE) were determined. Among 9 experimental substrates, the most suitable substrate for mycelial growth was 45ZMS:45S, followed by 45PRS:45S; their mycelial growth rates were obviously quicker than that of the control substrate. The BEs of all the experimental substrates respectively containing P. repens stalk, P. purpureum stalk and Z. mays stalk were higher than that of the control (39.55%) during the 2.5 months of cultivation period. The best substrate in terms of BE was 60ZMS:30S (58.33%), followed by 45PRS:45S (57.16%), 45ZMS:45S (49.86%), and 30ZMS:60S (47.20%). Based on the BE of the tested substrates, Z mays stalk appeared to be the best alternative material for the production of P. pulmonarius.
An antifungal protein (HM-af) was purified from the culinary-medicinal mushroom Hypsizygus marmoreus. The results of sodium dodecyl sulfate polyacrylamide gel electrophoresis and matrix-assisted laser desorption ionization time-of-flight mass spectrometry of HM-af indicated that its molecular mass was 9.5 kDa. The N-terminal amino acid sequence of HM-af showed homology to ribonuclease H from Clostridium thermocellum. HM-af showed the antifungal activity against Flammulina velutipes.
Cell Cytotoxicity of Coprinus comatus 306 Extracts 
Breast cancer is the most commonly diagnosed cancer among women. Currently, there is no effective therapy for malignant estrogen-independent breast cancer. In our study, we used hydrogen peroxide, a well-known strong oxidative reagent capable of activating the nuclear factor kappa B (NF-kappaB) transcription factor. The IC50 value of the culinary-medicinal Shaggy Inc Cap mushroom Coprinus comatus culture liquid crude extract on MCF7 cell viability was found to be as low as 76 microg/mL, and the IC50 value of C. comatus ethyl acetate extract was only 32 microg/ mL. Our results also showed that both extracts significantly affected IkappaBalpha phosphorylation in a dose-dependent manner. The effect of ethyl acetate extract was comparable to the effect of curcumin, a known NF-kappaB pathway inhibitor, and seemed to be the most active inhibitor of H2O2-dependent IkappaBalpha phosphorylation. In addition, the data obtained showed that only ethyl acetate extract inhibited the activity of IKK complex, at close to 90% as compared to the control of the untreated sample. These results suggest that C. comatus contains potent compounds capable of inhibiting NF-kappaB function and also possibly acts as an antitumor agent.
Skeleton of protoilludan. 
Recently, studies have been conducted on the chemical composition of fruiting bodies of the culinary-medicinal Honey mushroom, Armillaria mellea (Vahl.) P. Kumm. (higher Basidiomycetes). It is considered in Europe and Asia as edible and medicinal, when appropriately prepared, and has demonstrated the presence of different groups of organic compounds, including carbohydrates, sterols, sphingolipids, fatty acids, sesquiterpenes, non-hallucinogenic indole compounds, peptides, enzymes, adenosine derivatives, and many other components. Most of these metabolite groups possess potential therapeutic and dietary values. The results of quantitative analyses of indole compounds and heavy metals signal potential health hazards for humans. Some of the studies reviewed herein describe in detail the mechanism of symbiosis between A. mellea and the orchid species Gastrodia elata. This orchid is native to Asia, Australia, and New Zealand, and is used in therapeutics in official Chinese medicine.
The Royal Sun mushroom, the Himematsutake culinary-medicinal mushroom, Agaricus brasiliensis has several polyphenoloxidase activities in a broad sense. Here we report the partial purification of tyrosinase-type polyphenoloxidase (PPO). PPO is purified from A. brasiliensis without browning using a two-phase partitioning with Triton X-114 and ammonium sulfate fractionation. Partially denaturing SDS-PAGE (sodium dodecyl sulfate-polyacrylamide electrophoresis) staining with L-3,4-dihydroxyphenylalanine was performed and the indicated molecular sizes were approximately 70 kDa and 45 kDa. The purified enzyme is in its latent state and can be activated maximally in the presence of 1.6 mM sodium dodecyl sulfate (SDS). This enzyme catalyzes two distinct reactions, monophenolase and diphenolase activity, and the monophenolase activity showed a lag time typical of polyphenoloxidase. The K(m) value for 4-tert-butylcatechol was quite similar in the presence and absence of SDS, but the apparent V(max) value was increased 2.0-fold by SDS. Mimosine was a typical competitive inhibitor with K(i) values of 138.2 microM and 281.0 microM n the presence and absence of SDS, respectively.
This study investigated the effects of Agaricus brasiliensis S. Wasser et al. (=Agaricus blazei Murrill sensu Heinem.) aqueous extract on small intestinal sIgA levels, serum TNF-alpha, IFN-gamma and IL-10 levels, splenic index, bacterial translocation, and histology of small intestine, spleen, and liver from mice orally challenged with 10(6) CFU of Salmonella enterica serovar Typhimurium (SEST). Splenic index values as well as sIgA, TNF-alpha, IFN-gamma, and IL-10 levels were not affected by either A. brasiliensis aqueous extract treatment or by pathogenic challenge. Typical colonies of SEST were recovered from liver, spleen, and mesenteric lymph nodes of challenged animals, but there was no significant difference in this translocation between groups treated or not with A. brasiliensis aqueous extract. Translocation was confirmed by histopathological analysis in mice challenged with SEST, which showed small and diffuse foci of mixed inflammatory infiltrate in hepatic parenchyma. In conclusion, A. brasiliensis aqueous extract as tested in the present study did not influence any of the variables selected to evaluate in vivo its immunomodulatory effect suggested in the literature.
Culinary-medicinal mushrooms are able to lower blood cholesterol levels in animal models by different mechanisms. They might impair the endogenous cholesterol synthesis and exogenous cholesterol absorption during digestion. Mushroom extracts, obtained using pressurized water extractions (PWE) from Agaricus bisporus basidiomes, supplemented or not supplemented with selenium, were applied to HepG2 cell cultures to study the expression of 19 genes related to cholesterol homeostasis by low-density arrays (LDA). Only the PWE fractions obtained at 25°C showed 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) inhibitory activity. Besides the enzymatic inhibition, PWE extracts may downregulate some of the key genes involved in the cholesterol homeostasis, such as the squalene synthase gene (FDFT1), since its mRNA expression falls by one third of its initial value. In summary, A. bisporus extracts may also modulate biological cholesterol levels by molecular mechanisms further than the enzymatic way previously reported.
The Royal Sun medicinal mushroom, Agaricus brasiliensis, is used as a natural health product. In Japan, however, the quality control of some of these mushroom products has been viewed as a safety problem. Focusing on the quality control of A. brasiliensis KA21, we have performed several safety studies. To date, we have established evidence that this mushroom can be used safely as an immunostimulant and to mediate biochemical parameters associated with obesity or diabetes. Furthermore, to improve the manufacturing process of this mushroom, we have studied the relationship between its pharmaceutical actions and the conditions of its cultivation and thermal management. The purpose of this review is to report the findings of basic and clinical studies of the fruit body of A. brasiliensis KA21.
The effect of culinary-medicinal Royal Sun Agaricus (Agaricus brasiliensis) hot water extract on methyl methane sulfonate (MMS) induced mutagenicity/genotoxity in Drosophila melanogaster was studied using a quick and broadly applicable in vivo assay, i.e., the wing somatic mutation and recombination test. We used 2nd instar larvae, trans-heterozygous for the third chromosome recessive markers, i.e., multiple wing hairs (mvh) and flare-3 [flr (3)], and fed them for 24 h with the aqueous extract of A. brasiliensis. For antigenotoxicity studies a 24-h pretreatment with the extract was done, followed by a 48-h treatment of the then 3rd instar larvae with MMS. The frequency of mutations of the wing blade changes (i.e., of the number of wing spots of different sizes) induced in somatic cells was determined as a parameter of genetic changes of the wing imaginal discs. The results showed that A. brasiliensis extract did not cause any genotoxic or mutagenic effects. No antigenotoxic and/or protective effect against the induction of mutations by MMS was observed. Instead, a possible enhanced mitotic recombination frequency by MMS was seen after pretreatment of the larvae with A. brasiliensis extract. Possible mechanisms of action are discussed.
Agaricus brasiliensis currently is one of the most studied fungi because of its nutritional and therapeutic properties as an anti-inflammatory agent and an adjuvant in cancer chemotherapy. The effects of orally administered aqueous A. brasiliensis extract (14.3- and 42.9-mg doses) on parenchymal lung damage induced by carcinogenic 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) were observed in Wistar rats. NNK treatment induced pulmonary inflammation, but not lung cancer, in the rats. The lungs of animals treated with NNK showed a higher level of inflammation than those of the control group according to histopathologic examinations (P < 0.01) and kurtosis analysis (P < 0.001) of a global histogram generated from thoracic computed tomography scans. There was no significant difference in the alveolar and bronchial exudates between animals treated with a 14.3-mg dose of A. brasiliensis extract and the control without NNK. However, a significant difference was found between animals treated with NNK, received a 42.9-mg dose of A. brasiliensis (P < 0.05), and the controls not treated with NNK. We did not observe a significant difference between the kurtoses of the A. brasiliensis (14.3 mg) and control groups. However, a 42.9-mg dose of A. brasiliensis resulted in lower kurtosis values than those observed in the control group (P < 0.001). In conclusion, a low dose of A. brasiliensis was more effective in attenuating pulmonary inflammation. Similar to the histopathological results, the computed tomography scans also showed a protective effect of A. brasiliensis at the lower dose, which prevented gross pulmonary consolidation.
Culinary-medicinal Royal Sun mushroom, Agaricus brasiliensis (AbS), has traditionally been used for the prevention of a range of diseases, including cancer, hepatitis, atherosclerosis, hypercholesterolemia, diabetes, and dermatitis. The hepatoprotective effect of the fermented mushroom of A. brasiliensis (FMAE) and wild-growing A. brasiliensis (WMAE) were studied in this paper. An in vivo study of carbon tetrachloride (CCl4)-induced antioxidant activity in 2-month-old rats was conducted by examining the levels of activities of alanine aminotransaminase (ALT) and aspartate aminotransaminase (AST) and the antioxidant enzymes, including glutathione peroxidase (GSHPx) and catalase (CAT). Rats were divided into four groups, each containing six rats. The first group served as a control group. The second group was the CCl4 group. Group I and group II were treated orally with distilled water for 14 days respectively. Group III and Group IV were treated orally by WMAE and FMAE at oral doses of 50 mg/kg-day, respectively. Both WMAE and FMAE could reduce CCl4-induced toxicity, particularly hepatotoxicity, by suppressing ALT and AST activities, and increasing antioxidant enzyme activity. The studies demonstrate that both the fermented and wild-growing A. brasiliensis could protect the liver against CCl4-induced oxidative damage in rats.
We investigated the anxiolytic effects Agaricus brasiliensis extract (AbSE) on ischemia-induced anxiety using the plus-maze test and the social interaction test. The animals were treated orally with AbSE (4, 8, and 10 mg/kg/d, respectively) for 30 d, followed by middle cerebral artery occlusion-induced cerebral ischemia. Levels of noradrenaline, dopamine, and serotonin in the cerebral cortex of rats, as well as oxidative stress and plasma corticosterone levels were analyzed, respectively. The rota-rod test was carried out to exclude any false positive results in experimental procedures related to anxiety disorders, and the catalepsy test was carried out to investigate whether AbSE induces catalepsy. Our results demonstrate that oral administration of AbSE presented anxiolytic-like effects in the elevated plus-maze test and the social interaction test. Furthermore, AbSE did not induce extrapyramidal symptoms in the catalepsy test. The mechanism underlying the anxiolytic effect of AbSE might be increased brain monoamine levels and plasma corticosterone levels and decreased oxidative stress in cerebral ischemia/reperfusion rats.
As part of the safety evaluation of culinary-medicinal Royal Sun Agaricus, Agaricus brasiliensis KA21, for human consumption, we performed the bacterial reverse mutation test, the mouse micronucleus test, and mouse lymphoma test using A. brasiliensis KA21 as the test substance. The reverse mutation test utilized five bacterial strains, including Salmonella typhimurium TA100, TA1535, TA98, and TA1537, and Escherichia coli WP2 uvrAO. For the micronucleus test we used mice. For the mouse lymphoma test, we used one of the most commonly used mammalian cell mutagenesis systems; the L5178YTK +/- mouse lymphoma-TK assay detects the mutations at the thymidine kinase locus caused by base-pair changes, frameshift, and small deletions. All the tests were conducted according to the guidelines for genotoxicity testing of drugs by the Ministry of Health, Labor, and Welfare, Japan. In the bacterial reverse mutation test, no toxicity was observed up to a dose of 5,000 μg/plate. In the mouse micronucleus test, no toxicity was noted up to a dose of 1 g/kg body weight. In the mouse lymphoma test, frequency of the mutation was equal both in the presence or absence of KA21. Supporting the long history of human consumption of A. brasiliensis, the data shown in this study strongly indicate the safety of this mushroom.
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Jeng-Leun Mau
Shufeng Zhou
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