ABSTRACT
Tropomyosin receptor kinase B (TrkB) serves as a pivotal factor in various cancers. To identify novel natural compounds with TrkB-inhibiting properties, a screening approach was applied using extracts from a collection of wild and cultivated mushroom fruiting bodies, and Ba/F3 cells that ectopically express TrkB (TPR-TrkB). We selected mushroom extracts that selectively inhibited proliferation of the TPR-TrkB cells. We then evaluated the ability of exogenous interleukin 3 to rescue growth inhibition by the selected TrkB-positive extracts. An ethyl acetate extract of Auricularia auricula-judae actively inhibited auto-phosphorylation of TrkB. LC-MS/MS analysis of this extract revealed substances that might be responsible for the observed activity. This screening approach demonstrates, for the first time, that extracts originating from the mushroom A. auricula-judae exhibit TrkB-inhibition properties that might hold therapeutic potential for TrkB-positive cancers.
ABSTRACT
We have recently demonstrated that we could enhance glucan content in Pleurotus eryngii following cultivation of the mushrooms on a substrate containing different concentrations of olive mill solid waste (OMSW). These changes are directly related to the content of OMSW in the growing substrate. Using dextran sulfate sodium (DSS)-in-flammatory bowel disease (IBD) mice model, we measured the colonic inflammatory response to the different glucan preparations. We found that the histology damaging score (HDS) resulting from DSS treatment reach a value of 11.8 ± 2.3 were efficiently downregulated by treatment with the fungal extracted glucans. Glucans extracted from stalks cultivated at 20% OMSW downregulated to a HDS value of 6.4 ± 0.5 whereas those cultivated at 80% OMSW showed the strongest effects (5.5 ± 0.6). Similar downregulatory effects were obtained for expression of various intestinal cytokines. All tested glucans were equally effective in regulating the number of CD14/CD16 monocytes from 18.2 ± 2.7% for DSS to 6.4 ± 2.0 for DSS + glucans extracted from stalks cultivated at 50% OMSW. We tested the effect of glucans on lipopolysaccharide-induced production of TNF-α, which demonstrated that stalk-derived glucans were more effective than caps-derived glucans. Isolated glucans competed with anti-Dectin-1 and anti-CR3 antibodies, indicating that they contain ß-glucans recognized by these receptors. In conclusion, the most effective glucans in ameliorating IBD-associated symptoms induced by DSS treatment in mice were glucan extracts prepared from the stalk of P. eryngii grown at higher concentrations of OMSW. We conclude that these stress-induced growing conditions may be helpful in selecting more effective glucans derived from edible mushrooms.
Subject(s)
Glucans/pharmacology , Immunologic Factors/pharmacology , Inflammatory Bowel Diseases/drug therapy , Pleurotus/chemistry , Agaricales/chemistry , Cytokines/metabolism , Gene Expression Regulation/drug effects , Glucans/isolation & purification , Humans , Immunologic Factors/isolation & purification , Inflammation/drug therapy , Olea , Pleurotus/growth & development , Tumor Necrosis Factor-alpha/metabolism , beta-Glucans/isolation & purification , beta-Glucans/pharmacologyABSTRACT
: Pleurotus eryngii is recognized for its prominent nutritional and medicinal value. In our study, we tested the effect of glucans on lipopolysaccharide (LPS)-induced production of TNF-α. We demonstrated that glucan extracts are more effective than mill mushroom preparations. Additionally, the effectiveness of stalk-derived glucans were slightly more pronounced than of caps. Cap and stalk glucans from mill or isolated glucan competed dose-dependently with anti-Dectin-and anti-CR-3 antibodies, indicating that they contain ß-glucans recognized by these receptors. Using the dextran sulfate sodium (DSS)-inflammatory bowel disease mice model, intestinal inflammatory response to the mill preparations was measured and compared to extracted glucan fractions from caps and stalks. We found that mill and glucan extracts were very effective in downregulating IFN-γ and MIP-2 levels and that stalk-derived preparations were more effective than from caps. The tested glucans were equally effective in regulating the number of CD14/CD16 monocytes and upregulating the levels of fecal-released IgA to almost normal levels. In conclusion, the most effective glucans in ameliorating some IBD-inflammatory associated symptoms induced by DSS treatment in mice were glucan extracts prepared from the stalk of P. eryngii. These spatial distinctions may be helpful in selecting more effective specific anti-inflammatory mushrooms-derived glucans.
Subject(s)
Anti-Inflammatory Agents/pharmacology , Colitis, Ulcerative/drug therapy , Fruiting Bodies, Fungal/chemistry , Fungal Polysaccharides/pharmacology , Pleurotus/chemistry , Animals , Anti-Inflammatory Agents/therapeutic use , Cell Line , Female , Fungal Polysaccharides/analysis , Fungal Polysaccharides/therapeutic use , Macrophages/drug effects , Macrophages/metabolism , Mice , Mice, Inbred BALB CABSTRACT
The possibility of usage mushroom industry wastage, as a source of antimicrobial biopolymer chitosan to form active edible coatings was studied. It was found that the champignon stipe, an underutilized part of the mushroom, gave rise to a higher chitosan yield than caps (176 vs. 105â¯mg/g). Fungal chitosan caused a total growth inhibition of the Saccharomyces cerevisiae yeast and Escherichia coli bacteria at concentrations of 1% and 2%, respectively. The fungal chitosan-based edible coatings were applied on fresh-cut melons and found to enhance fruit firmness, inhibit off-flavors and reduce the microbial counts (up to 4â¯logâ¯CFU/g). Volatiles profile showed the coated melons have a higher content of esters responsible for fruit flavor (79.93% and 57.15% for fungal chitosan coated melon and uncoated melon, respectively). This study demonstrates that waste from the mushroom industry can be utilized for the production of non-animal sourced chitosan to form active edible coatings.
Subject(s)
Chitosan/pharmacology , Cucurbitaceae/microbiology , Food Preservation/methods , Agaricales , Chitosan/isolation & purification , Food Preservatives/pharmacology , FruitABSTRACT
Mushroom polysaccharides are edible polymers that have numerous reported biological functions; the most common effects are attributed to ß-glucans. In recent years, it became apparent that the less abundant α-glucans also possess potent effects in various health conditions. Here we explore several Pleurotus species for their total, ß and α-glucan content. Pleurotus eryngii was found to have the highest total glucan concentrations and the highest α-glucans proportion. We also found that the stalks (stipe) of the fruit body contained higher glucan content then the caps (pileus). Since mushrooms respond markedly to changes in environmental and growth conditions, we developed cultivation methods aiming to increase the levels of α and ß-glucans. Using olive mill solid waste (OMSW) from three-phase olive mills in the cultivation substrate. We were able to enrich the levels mainly of α-glucans. Maximal total glucan concentrations were enhanced up to twice when the growth substrate contained 80% of OMSW compared to no OMSW. Taking together this study demonstrate that Pleurotus eryngii can serve as a potential rich source of glucans for nutritional and medicinal applications and that glucan content in mushroom fruiting bodies can be further enriched by applying OMSW into the cultivation substrate.
Subject(s)
Glucans/metabolism , Olea/chemistry , Pleurotus/metabolism , Waste Products , Eucalyptus/chemistry , Glucans/isolation & purification , Pleurotus/growth & development , beta-Glucans/metabolismABSTRACT
Vitamin D has been known for its anti-inflammatory properties. Extracts derived from Lentinula edodes (Shiitake) edible mushroom exert an anti-inflammatory effect. These extracts contain high levels of ergosterol, which converts into ergocalciferol (vitamin D2) following exposure to ultraviolet light, followed by absorption and hydroxylation into the active form 25-hydroxyvitamin D [25(OH)D]. To determine the anti-inflammatory effect of overexpression of vitamin D in edible mushrooms, L. edodes mushrooms were exposed to ultraviolet-B light, freeze-dried, followed by measurement of vitamin D2 contents, in their dry weight. C57B1/6 mice were orally treated with vitamin D2-enriched or nonenriched mushroom extract prior and during concanavalin A-immune-mediated liver injury. Exposure to ultraviolet light increased vitamin D2 content in Shiitake edible mushrooms. Following feeding of vitamin D-enriched mushroom extracts to mice with immune-mediated hepatitis, a significant decrease in liver damage was noted. This was shown by a decrease in alanine aminotransferase and aspartate aminotransferase serum levels, a decrease in proportion of mice with severe liver injury, and by improvement in liver histology. These effects were associated with a decrease in serum interferon gamma levels. A synergistic effect was noted between the anti-inflammatory effect of the mushroom extracts and that of vitamin D. Oral administration of vitamin D-enriched L. edodes edible mushroom exerts a synergistic anti-inflammatory effect in the immune-mediated hepatitis. The data support its potential use as safe immunomodulatory adjuvant for the treatment of HCV and nonalcoholic steatohepatitis.
Subject(s)
Anti-Inflammatory Agents/administration & dosage , Ergocalciferols/administration & dosage , Hepatitis/drug therapy , Plant Extracts/administration & dosage , Protective Agents/administration & dosage , Shiitake Mushrooms/chemistry , Vegetables/chemistry , Alanine Transaminase/immunology , Animals , Anti-Inflammatory Agents/analysis , Ergocalciferols/analysis , Hepatitis/immunology , Humans , Liver/drug effects , Liver/immunology , Male , Mice , Mice, Inbred C57BL , Plant Extracts/analysis , Protective Agents/analysis , Protective Agents/isolation & purification , Shiitake Mushrooms/radiation effects , Ultraviolet Rays , Vegetables/radiation effectsABSTRACT
AIM: To determine the immunomodulatory effect of Shiitake (a mushroom extract), we tested its effect on liver-mediated immune regulation in a model of immune-mediated colitis. METHODS: Four groups of mice were studied. Colitis was induced by intracolonic instillation of TNBS in groups A and B. Groups A and C were treated daily with Shiitake extract, while groups B and D received bovine serum albumin. Mice were evaluated for development of macroscopic and microscopic. The immune effects of Shiitake were determined by FACS analysis of intra-hepatic and intrasplenic lymphocytes and IFN-gamma ELISPOT assay. RESULTS: Administration of Shiitake resulted in marked alleviation of colitis, manifested by significant improvement in the macroscopic and microscopic scores, and by reduction in IFN-gamma-producing colonies in group A, compared to group B mice (1.5 pfu/mL vs 3.7 pfu/mL, respectively). This beneficial effect was associated with a significant increase in the intra-hepatic CD8(+) lymphocyte trapping, demonstrated by an increased intrasplenic/intrahepatic CD4/CD8 lymphocyte ratio. These effects were accompanied by a 17% increase in the number of intrahepatic natural killer T (NKT) cells. A similar effect was observed when Shiitake was administered to animals without disease induction. CONCLUSION: Shiitake extract affected liver-mediated immune regulation by altering the NKT lymphocyte distribution and increasing intrahepatic CD8(+) T lymphocyte trapping, thereby leading to alleviation of immune-mediated colitis.