Redox modulation of cellular stress response and lipoxin A4 expression by Coriolus versicolor in rat brain: Relevance to Alzheimer's disease pathogenesis.

Increasing evidence supports the notion that oxidative stress-driven neuroinflammation is an early pathological feature in neurodegenerative diseases. As a prominent intracellular redox system involved in neuroprotection, the vitagene system is emerging as a potential neurohormetic target for novel cytoprotective interventions. Vitagenes encode for cytoprotective heat shock proteins 70, heme oxygenase-1, thioredoxin and lipoxin A4. Emerging interest is now focusing on molecules capable of activating the vitagene system as novel therapeutic targets to minimize deleterious consequences associated with free radical-induced cell damage, such as in neurodegeneration. Mushroom-derived lipoxin A4 (LXA4) is an emerging endogenous eicosanoid able to promote resolution of inflammation, acting as an endogenous "braking signal" in the inflammatory process. Mushrooms have long been used in traditional medicine for thousands of years, being now increasingly recognized as rich source of polysaccharopeptides endowed with significant antitumor, antioxidant, antiviral, antibacterial and cytoprotective effects, thereby capable of stimulating host immune responses. Here we provide evidence of a neuroprotective action of the Coriolus mushroom when administered orally to rat. Expression of LXA4 was measured in different brain regions after oral administration of a Coriolus biomass preparation, given for 30 days. LXA4 up-regulation was associated with an increased content of redox sensitive proteins involved in cellular stress response, such as Hsp72, heme oxygenase-1 and thioredoxin. In the brain of rats receiving Coriolus, maximum induction of LXA4 was observed in cortex and hippocampus. Hsps induction was associated with no significant changes in IkBα, NFkB and COX-2 brain levels. Conceivably, activation of LXA4 signaling and modulation of stress-responsive vitagene proteins could serve as a potential therapeutic target for AD-related inflammation and neurodegenerative damage.

Transformation of multi-component ginkgolide into ginkgolide B by Coprinus comatus.

BACKGROUND: As the strongest antagonist of the platelet activating factor, ginkgolide B (GB) possesses anti-ischemic, anti-oxidant and anti-convulsant properties, and it is used for the treatment of thrombosis in clinical practice. Till now, GB is usually obtained from extraction of Ginkgo biloba leaves through column chromatography with an extremely low yield and high cost, which can not meet clinical requirement. Therefore, it is urgent to find a new method to prepare GB. RESULTS: In the current study, we studied the ability and mechanism to transform multi-component ginkgolide into GB by Coprinus comatus in order to enhance the GB yield. Except for ginkgolide A (GA) and GB, all the other ginkgolides in the extract were transformed by the strain. In the case of culture medium containing 20 g/L glucose, the transformation product was identified as 12% GA and 88% GB by high performance liquid chromatography-Mass spectrometry (HPLC-MS), two stage mass spectrometry (MS/MS) and nuclear magnetic resonance (NMR). Partial GA was also transformed into GB according to the yield (76%) and the content of GA in the raw ginkgolide (28.5%). Glucose was the key factor to transform ginkgolides. When glucose concentration in medium was higher than 40 g/L, all ginkgolides were transformed into the GB. Proteomic analysis showed that C. comatus transformed ginkgolide into GB by producing 5 aldo/keto reductases and catalases, and enhancing the metabolism of glucose, including Embden-Meyerhof pathway (EMP), hexose monophophate pathway (HMP) and tricarboxylic acid (TCA). CONCLUSIONS: C. comatus could transform ginkgolides into GB when the medium contained 40 g/L glucose. When the strain transformed ginkgolides, the glucose metabolism was enhanced and the strain synthesized more aldo/keto reductases and catalases. Our current study laid the groundwork for industrial production of GB.

Statistical Optimization of the Content Composition Precursors Using Response Surface Methodology to Enhance Agaricoglyceride A Production from the Shaggy Ink Cap Medicinal Mushroom, Coprinus comatus (Higher Basidiomycetes) Mycelia.

Coprinus comatus, a novel cultivated edible mushroom, has a various of pharmacological effects due to its many active components. In this study, agaricoglycerides, a new class of fungal secondary metabolites that have strong activity against neurolysin, were isolated from C. comatus mycelia. Simultaneously, a 3-level Box-Behnken factorial design was used, combined with response surface methodology, to optimize the precursor composition of agaricoglycerides for the production of agaricoglyceride A. The model estimated that a maximal yield of agaricoglyceride A (20.105 mg/L) could be obtained when the concentrations of 4-hydroxybenzoic acid, glycerol, and methanol (MeOH) were set at 75 mg/L, 0.75 mL/L, and 0.75 mL/L, respectively. The verified experiments showed that the model was significantly consistent with the model prediction. These results showed that appropriately adding the precursors could increase the production of agaricoglyceride A.

Anti-inflammatory effects of fermented and non-fermented Sophora flavescens: a comparative study.

BACKGROUND: The roots of Sophora flavescens (Leguminosae) have been used in East Asian countries as an herbal medicine and a food ingredient for thousands of years. The aim of the present study was to investigate the effects of S. flavescens fermentation on endotoxin-induced uveitis (EIU) in rats. METHODS: EIU was induced in rats via a footpad injection of lipopolysaccharide (LPS). Immediately after the LPS inoculation, fermented and non-fermented extracts of S. flavescens (FSE and NFSE, respectively) were administered orally, and the aqueous humor was collected from both eyes 24 hours later. The anti-inflammatory effects of FSE and NFSE were examined in terms of regulation of nuclear factor kappa B (NF-κB) activation and the expression of interleukin-1ß (IL-1ß), tumor necrosis factor-α (TNF-α), inducible nitric oxide synthase (iNOS), intercellular cell adhesion molecule (ICAM)-1, and cyclooxygenase-2 (COX-2). The regulation of maleic dialdehyde (MDA) levels and polymorphonuclear cell (PMN) infiltration by FSE and NFSE were also examined. RESULTS: Treatment with FSE significantly inhibited LPS-induced increases in IL-1ß and TNF-α production and the expression of iNOS, ICAM-1 and COX-2. Moreover, FSE suppressed LPS-induced NF-κB activation, and reduced both MDA levels and infiltration by PMN. CONCLUSION: These results indicate that solid state fermentation may enhance the anti-inflammatory effects of S. flavescens.

Determination of trace elements in three mushroom samples of basidiomycetes from Shandong, China.

We have determined the trace element composition of three mushrooms of Basidiomycetes, used in traditional Chinese medicine using atomic absorption spectrophotometer (AAS). Metal concentrations in mushrooms were 203-401 mg/kg for iron, 22-51 mg/kg for manganese, 84-116 mg/kg for zinc, 24.1-41.3 mg/kg for copper, 1.6-5.6 mg/kg for lead, 3.3-4.4 mg/kg for chromium, 9.3-11.5 mg/kg for nickel, 0 mg/kg for vanadium, and 55.3-71 mg/kg for magnesium. The trace metal concentrations in mushrooms are hardly affected by the ecosystem and soil where they grew, as well as by the mushroom species and trace metal species. The results can be used to set new standards to control the quality of the three mushrooms of Basidiomycetes-Ganoderma lucidum, Coprinus comatus, and Grifola frondosa.

Induction of apoptosis by Coprinus disseminatus mycelial culture broth extract in human cervical carcinoma cells.

Extract of Coprinus disseminatus (pers. Fr.) (C. disseminatus) culture broth (EDCB) inhibits proliferation and induces apoptosis in the human cervical carcinoma cells at 5 microg/ml. To determine whether the cell death induced by the EDCB recruits caspases or not, one of the exclusive pathways in cell death, we examined caspase-3 activity in this cell death process. The activity of caspase-3 was remarkably increased when the cell was treated with EDCB, and this activity was nullified by Z-VAD-FMK, a well known caspase-3 inhibitor. From these results, we would expect the EDCB to contain substances with the ability to induce apoptosis in the human cervical carcinoma cells. The extent of the EDCB induced apoptosis is cell line-dependent.

[Isolation and identification of an antileukemia substance from Coprinus radiatus]. / Vydelenie i identifikatsiia protivoleikoznogo veshchestva iz Coprinus radiatus.

Conditions for cultivation of basidiomycete Coprinus radiatus on agar media and its submersion fermentation were developed. An antibiotic was isolated from the fermentation broth filtrate by extraction with ethyl acetate followed by purification on a column with silica gel. The antibiotic had a pronounced in vivo effect on hemoblastosis La. Spectral analysis of the antibiotic (UV, IR, NMR and mass spectra) showed that it was identical to patulin (a toxin).

Production of protein by fungi from agricultural wastes. III. Effect of phosphorus on the efficiency of substrate utilization and protein production by Rhizoctonia melongina, Pleurotus ostreatus, and Coprinus aratus.

An attempt was made to select a source of phosphorus that is readily available and ensures maximum protein efficiency for Rhizoctonia melongina, Pleurotus ostreatus, and Coprinus aratus, using sugarcane bagasse for the former two and wheat straw for the latter one in the liquid medium. Of the six different phosphorus compounds tested, urea phosphate was unanimously preferred by the three fungi. The concentration of urea phosphate for maximum protein output was then standardized.