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At least 163 records · Page 9Linked to original sources

PubMed2007

Ganoderma lucidum polysaccharide peptide reduced the production of proinflammatory cytokines in activated rheumatoid synovial fibroblast.

The aim of the current study was to elucidate the potential therapeutic effect of Ganoderma lucidum polysaccharide peptide (GL-PP) in rheumatoid arthritis (RA). The effects of GL-PP on cell proliferation and cytokine production were studied in RA synovial fibroblasts (RASF). GL-PP significantly inhibited the proliferation of RASF. Following the incubation with GL-PP, production of interleukin (IL)-6 and monocyte chemoattractant protein (MCP)-1 in RASF were significantly increased as expressed as percentage change from basal values. However, the actual effects were minimal due to the low basal values. When RASF were activated by IL-1beta or lipopolysaccharides, IL-8 and MCP-1 production increased many folds. GL-PP significantly suppressed their productions. The inhibitory effects of GL-PP on cytokine production in RASF were at least in part, by inhibiting the nuclear factor-kappa B (NF-kappaB) transcription pathway. Our results demonstrated that GL-PP had the unique ability to modulate cytokine production in RASF and warrants further investigation into its mechanism of action.

Arthritis, Rheumatoid↗

PubMed2004

A distinctive ribonuclease from fresh fruiting bodies of the medicinal mushroom Ganoderma lucidum.

A ribonuclease with an N-terminal sequence distinct from other mushroom ribonucleases was isolated from fresh fruiting bodies of the medicinal mushroom Ganoderma lucidum. The ribonuclease was adsorbed on DEAE-cellulose and Q-Sepharose, and unadsorbed on CM-Sepharose. It possessed a molecular mass of 42 kDa as judged by gel filtration by fast protein liquid chromatography on Superdex 75 and sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Its molecular mass was similar to that of straw mushroom ribonuclease but much higher compared with those of other mushroom ribonucleases. The ribonuclease was unique among mushroom ribonucleases in that it exhibited the highest potency toward poly(U), followed by poly(A). Its activity toward poly(G) and poly(C) was about one-half of that toward poly(A) and one-quarter of that toward poly(U). A pH of 4.0 and a temperature of 60 degrees C were required for optimal activity of the enzyme. The optimum pH was low compared with those reported for other mushroom ribonucleases.

Agaricales↗

PubMed2004

Immune receptors for polysaccharides from Ganoderma lucidum.

This study was designed to identify and characterize the immune receptors for polysaccharides from Ganoderma lucidum, a Chinese medicinal fungus that exhibits anti-tumor activities via enhancing host immunity. We herein demonstrate that G. lucidum polysaccharides (GLPS) activated BALB/c mouse B cells and macrophages, but not T cells, in vitro. However, GLPS was unable to activate splenic B cells from C3H/HeJ mice that have a mutated TLR4 molecule (incapable of signal transduction) in proliferation assays. Rat anti-mouse TLR4 monoclonal antibody (Ab) inhibited the proliferation of BALB/c mouse B cells under GLPS stimulation. Combination of Abs against mouse TLR4 and immunoglobulin (Ig) achieved almost complete inhibition of GLPS-induced B cell proliferation, implying that both membrane Ig and TLR4 are required for GLPS-mediated B cell activation. In addition, GLPS significantly inhibited the binding of mouse peritoneal macrophages with polysaccharides from Astragalus membranaceus, which is known to bind directly with TLR4 on macrophage surface. Moreover, GLPS induced IL-1beta production by peritoneal macrophages from BALB/c, but not C3H/HeJ, mice, suggesting that TLR4 is also involved in GLPS-mediated macrophage activation. We Further identified a unique 31 kDa serum protein and two intracellular proteins (ribosomal protein S7 and a transcriptional coactivator) capable of binding with GLPS in co-precipitation experiments. Our results may have important implications for our understanding on the molecular mechanisms of immunopotentiating polysaccharides from traditional Chinese medicine.

Animals↗

PubMed2005

Ganoderma lucidum suppresses angiogenesis through the inhibition of secretion of VEGF and TGF-beta1 from prostate cancer cells.

Ganoderma lucidum (G. lucidum) is a popular medicinal mushroom that has been used as a home remedy for the general promotion of health and longevity in East Asia. The dried powder of G. lucidum, which was recommended as a cancer chemotherapy agent in traditional Chinese medicine, is currently popularly used worldwide in the form of dietary supplements. We have previously demonstrated that G. lucidum induces apoptosis, inhibits cell proliferation, and suppresses cell migration of highly invasive human prostate cancer cells PC-3. However, the molecular mechanism(s) responsible for the inhibitory effects of G. lucidum on the prostate cancer cells has not been fully elucidated. In the present study, we examined the effect of G. lucidum on angiogenesis related to prostate cancer. We found that G. lucidum inhibits the early event in angiogenesis, capillary morphogenesis of the human aortic endothelial cells. These effects are caused by the inhibition of constitutively active AP-1 in prostate cancer cells, resulting in the down-regulation of secretion of VEGF and TGF-beta1 from PC-3 cells. Thus, G. lucidum modulates the phosphorylation of Erk1/2 and Akt kinases in PC-3 cells, which in turn inhibits the activity of AP-1. In summary, our results suggest that G. lucidum inhibits prostate cancer-dependent angiogenesis by modulating MAPK and Akt signaling and could have potential therapeutic use for the treatment of prostate cancer.

Cell Line, Tumor↗

PubMed2004

Polysaccharides of Ganoderma lucidum alter cell immunophenotypic expression and enhance CD56+ NK-cell cytotoxicity in cord blood.

In our previous study, a fucose-containing glycoprotein fraction (F3), isolated from the water-soluble extracts of Ganoderma lucidum, was shown to stimulate mice spleen cell proliferation and cytokine expression. We now further investigate the effect of F3 on the immunophenotypic expression in mononuclear cells (MNCs). When human umbilical cord blood (hUCB) MNCs were treated with F3 (10-100 microg/mL) for 7days, the population of CD14+CD26+ monocyte/macrophage, CD83+CD1a+ dendritic cells, and CD16+CD56+ NK-cells were 2.9, 2.3, and 1.5 times higher than those of the untreated controls (p<0.05). B-cell population has no significant change. T cell growth was, however, slightly inhibited and CD3 marker expression decreased approximately 20% in the presence of higher concentrations of F3 (100 microg/mL). We also found that F3 is not harmful to human cells in vitro, and after F3 treatment, NK-cell-mediated cytotoxicity was significantly enhanced by 31.7% (p<0.01) at effector/target cell ratio (E/T) 20:1, but was not altered at E/T 5:1.

CD56 Antigen↗

PubMed2006

Structure-activity relationship for inhibition of 5alpha-reductase by triterpenoids isolated from Ganoderma lucidum.

In humans, 5alpha-reductase is involved in the development of benign prostatic hyperplasia. Triterpenoids isolated from ethanol extracts of Ganoderma lucidum (Fr.) Krast (Ganodermataceae) inhibited 5alpha-reductase activity. The presence of the C-3 carbonyl group and of the C-26-alpha,beta-unsaturated carbonyl group was characteristic of almost all inhibitors isolated from G. lucidum.

5-alpha Reductase Inhibitors↗

PubMed2004

Ganoderma lucidum extracts inhibit growth and induce actin polymerization in bladder cancer cells in vitro.

This study was conducted to investigate chemopreventive effects of Ganoderma lucidum using a unique in vitro human urothelial cell (HUC) model consisted of HUC-PC cells and MTC-11 cells. Ethanol and water extracts of fruiting bodies and spores of the G. lucidum were used to examine growth inhibition, actin polymerization status, and impact of actin remodeling on cell migration and adhesion. Results showed that ethanol extracts had a stronger growth inhibition effect than water extracts. Cell cycle analysis showed that the growth inhibition effect was associated with G2/M arrest. At non-cytotoxic concentrations (40-80 microg/ml), these extracts induced actin polymerization, which in turn inhibited carcinogen 4-aminobiphenyl induced migration in both cell lines. The increased actin polymerization was associated with increased stress fibers and focal adhesion complex formation, however, expression of matrix metalloproteinase-2 and focal adhesion kinase (total and phospholated) were unchanged, which suggests that other mechanisms may be involved.

Actins↗

PubMed2006

Enhanced induction of mitochondrial damage and apoptosis in human leukemia HL-60 cells by the Ganoderma lucidum and Duchesnea chrysantha extracts.

Combined treatment with the medicinal mushroom Ganoderma lucidum and the herb Duchesnea chrysantha extracts (GDE) causes a synergistic induction of mitochondrial damage and apoptosis in HL-60 cells. GDE treatment is selectively toxic to HL-60 leukemia cells whereas no cytotoxic effect is observed in normal peripheral blood mononuclear cells. GDE-induced apoptosis is associated with Bcl-2 down-regulation, Bax translocation, mitochondrial cytochrome c release and caspase-3 activation, suggesting that apoptosis by this combination occurs through the mitochondria-dependent pathway. The present findings suggest that this combination merits further investigation as a potential therapeutic agent for the treatment of cancer.

Amino Acid Chloromethyl Ketones↗

PubMed2004

Genetic transformation and mutant isolation in Ganoderma lucidum by restriction enzyme-mediated integration.

A white-rot basidiomycete Ganoderma lucidum has long been used as a medicinal mushroom in Asia, and it has an array of enzymes important for wood degrading activity. There have been many reports about the ingredients which show health aiding effects. In order to analyze gene functions and introduce foreign genes into this fungus, genetic transformation is required. We have successfully transformed G. lucidum to geneticin resistance using pJS205-1 which has the antibiotic resistance genes against geneticin and phosphinothricin. Many different mutants have been generated during the transformation by restriction enzyme mediated integration, and the transformation yield was 4-17 transformants (microg plasmid DNA)(-1). The plasmid was integrated stably into the recipient chromosome, which was confirmed by PCR with the plasmid-specific primers.

Cloning, Molecular↗

PubMed2004

Links between morphology and physiology of Ganoderma lucidum in submerged culture for the production of exopolysaccharide.

Ganoderma lucidum was grown in submerged culture in shake flasks on a medium containing peptone, yeast extract and glucose. In pre-cultures, inoculated from an agar-grown culture, morphological and metabolic events were linked: the pellets originally produced protuberances when glucose was present in the medium, although glucose was not consumed. The protuberances were then liberated into the medium as second-generation pellets, at which time glucose consumption began and the rate of exopolysaccharide (EPS) production increased. The synchrony between events was repeated in cultures fed with either glucose or peptone and yeast extract. In main cultures, inoculated from a 16-day-old pre-culture, the biomass concentration increased linearly, while glucose consumption and EPS production were initially slow but then accelerated. Protuberances were produced and liberated similarly to the pre-culture, but there was less synchrony amongst the pellets. When glucose was added to such a culture on day 10, an EPS concentration of 5.7 g L(-1) was achieved on day 13, this being the highest reliable EPS concentration yet reported for submerged culture of G. lucidum. We conclude that a greater understanding of the morphological and physiological events during the culture of G. lucidum will allow the proposal of culture strategies to improve EPS production.

Bioreactors↗

PubMed2004

Possible mode of action of antiherpetic activities of a proteoglycan isolated from the mycelia of Ganoderma lucidum in vitro.

A bioactive fraction (GLPG) was extracted and purified from the mycelia of Ganoderma lucidum by EtOH precipitation and DEAE-cellulose column chromatography. GLPG was a proteoglycan and had a carbohydrate:protein ratio of 10.4:1. Its antiviral activities against herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) were investigated by the cytopathic effect (CPE) inhibition assay in cell culture. This kind of polysaccharide inhibited the development of the cytopathic effect in dose-dependent manner in HSV-infected cells, moreover did not show any cytotoxic effects on cells even when a concentration was as high as 2000 microg/ml. In order to study the possible mode of action of the antiviral activity of GLPG, cells were treated with GLPG before, during and after infection, and the viral titers in the supernatant of cell culture 48 h post-infection were tested by TCID(50) assay. The antiviral effects in pre-treated and treated during virus infection with GLPG were more remarkable than the treatment of post-infection. Although the precise mechanism has yet to be defined, our work suggested that GLPG inhibits viral replication by interfering with the early events of viral adsorption and entry into target cells. Thus, this proteoglycan seems to be a potential candidate for anti-HSV agents.

Animals↗

PubMed2006

Ganoderma lucidum polysaccharides enhance the function of immunological effector cells in immunosuppressed mice.

The present study was designed to determine in vivo efficacy of Ganoderma lucidum polysaccharides (Gl-PS) for enhancing the activity of immunological effector cells in immunosuppressed mice. Mice were injected intraperitoneally (i.p.) once daily with low-dose (2.5mg/kg), intermediate-dose (25mg/kg), and high-dose (250 mg/kg) of Gl-PS, respectively, for 7 consecutive days 24h after i.p. injection of a immunosuppressing anti-tumor agent cyclophosphamide (Cy, 300 mg/kg). In Cy-treated mice, compared to vehicle, low-dose Gl-PS accelerated recovery of bone marrow cells, red blood cells and white blood cells, as well as splenic natural killer cells and natural killer T cells, and enhanced T and B cell proliferation responses on day 8, cytotoxic T lymphocyte activity on day 5, as well as NK cell and lymphokine activated killer cell activity on days 7-9. Furthermore, it promoted phagocytosis and cytotoxicity of macrophages on day 12. The above beneficial effects induced by the low-dose Gl-PS treatment did not result in any side effects. These results demonstrate the efficacious effects of low-dose Gl-PS treatment for enhancing the activity of immunological effector cells in immunosuppressed mice, and may provide a basis for applying this herb as an efficacious adjacent immunopotentiating therapy against cancer chemotherapy-induced immunosuppression.

Animals↗

PubMed2006

Quantitative determination of six major triterpenoids in Ganoderma lucidum and related species by high performance liquid chromatography.

A reversed-phase liquid chromatographic method was developed for the quantitative determination of six triterpenoids, namely ganoderic acids C2, B, AM1, K, H and D in Ganoderma lucidum and its related species. Samples were extracted with chloroform in ultrasonic bath. The optimal conditions of separation and detection were achieved on an Agilent Zorbax SB-C18 column (250 mmx4.6 mm, 5 microm), with a linear gradient of acetonitrile and 0.03% aqueous phosphoric acid (v/v), at a flow rate of 1.0 ml/min, detected at 252 nm. All calibration curves showed good linearity (r2>0.999) within test ranges. The relative deviation of this method was less than 2% for intra- and inter-day assays, and the percentage recovery of the method was 93-103%, with relative standard deviation (R.S.D.) less than 5%. The current assay method was applied to quantitative determination of constituents of triterpenoids in 36 different samples of G. lucidum and its related species. The results indicated that the developed method could be readily utilized as a quality control method for G. lucidum and related species.

Chromatography, High Pressure Liquid↗

PubMed2006

HPLC determination of four triterpenoids in rat urine after oral administration of total triterpenoids from Ganoderma lucidum.

A sensitive and simple high-performance liquid chromatography (HPLC) method was applied for the quantitative determination of four major triterpenoids (ganoderic acids C(2), B, K and H) in rat urine after oral administration of total triterpenoids from Ganoderma lucidum. The urine sample was extracted with dichloromethane-ethyl acetate (90:10) after acidification by hydrochloric acid (0.2 mol/ml). Chromatographic separation was achieved on a Zorbax SB-C(18) column (250 mm x 4.6 mm, 5 microm) at 35 degrees C, with a linear gradient of acetonitrile and 0.03% aqueous phosphoric acid (v/v), at a flow rate of 1.2 ml/min. The four triterpenoids and internal standard (hydrocortisone) were detected at a wavelength 252 nm. The within- and between-day assay coefficients of variation for the four triterpenoids in urine were less than 9% and the extraction recovery of this method was higher than 90%. Using this method, the excretion profile of the triterpenoids in rat urine after oral administration of total triterpenoids of G. lucidum was revealed for the first time.

Animals↗

PubMed2006

Ganoderma lucidum causes apoptosis in leukemia, lymphoma and multiple myeloma cells.

Over many centuries, herbal remedies have treated a variety of ailments. This empiric observational approach has produced a number of leads for formulated medicines. Ganoderma lucidum extract was screened for its anti-proliferative activity using a panel of 26 human cancer cell lines. The six most sensitive hematologic cell lines were: HL-60 (ED50 26 microg/ml), U937 (63 microg/ml), K562 (50 microg/ml), Blin-1 (38 microg/ml), Nalm-6 (30 microg/ml) and RPMI8226 (40 microg/ml). Cell cycle analyses revealed a G2/M arrest, most prominently in HL-60 cells. Four hematopoietic cell lines (HL-60, Blin-1, U937, RPMI8226) were examined for apoptosis, which ranged between 21 and 92%. After exposure to G. lucidum extract, HL-60 cells became multinucleated with an increased DNA content. These results indicate that G. lucidum extract has a profound activity against leukemia, lymphoma and multiple myeloma cells and may be a novel adjunctive therapy for the treatment of hematologic malignancies.

Apoptosis↗

PubMed2006

Ganoderic acid T from Ganoderma lucidum mycelia induces mitochondria mediated apoptosis in lung cancer cells.

Ganoderma lucidum is a well-known traditional Chinese medicinal herb containing many bioactive compounds. Ganoderic acid T (GA-T), which is a lanostane triterpenoid purified from methanol extract of G. lucidum mycelia, was found to exert cytotoxicity on various human carcinoma cell lines in a dose-dependent manner, while it was less toxic to normal human cell lines. Animal experiments in vivo also showed that GA-T suppressed the growth of human solid tumor in athymic mice. It markedly inhibited the proliferation of a highly metastatic lung cancer cell line (95-D) by apoptosis induction and cell cycle arrest at G(1) phase. Moreover, reduction of mitochondria membrane potential (Delta psi(m)) and release of cytochrome c were observed during the induced apoptosis. Our data further indicate that the expression of proteins p53 and Bax in 95-D cells was increased in a time-dependent manner, whereas the expression of Bcl-2 was not significantly changed; thus the ratio of Bcl-2/Bax was decreased. The results show that the apoptosis induction of GA-T was mediated by mitochondrial dysfunctions. Furthermore, stimulation of the activity of caspase-3 but not caspase-8 was observed during apoptosis. The experiments using inhibitors of caspases (Z-VAD-FMK, Z-DEVD-FMK and Z-IETD-FMK) confirmed that caspase-3 was involved in the apoptosis. All our findings demonstrate that GA-T induced apoptosis of metastatic lung tumor cells through intrinsic pathway related to mitochondrial dysfunction and p53 expression, and it may be a potentially useful chemotherapeutic agent.

Animals↗

PubMed2005

Ganodermin, an antifungal protein from fruiting bodies of the medicinal mushroom Ganoderma lucidum.

A 15-kDa antifungal protein, designated ganodermin, was isolated from the medical mushroom Ganoderma lucidum. The isolation procedure utilized chromatography on DEAE-cellulose, Affi-gel blue gel, CM-Sepharose and Superdex 75. Ganodermin was unadsorbed on DEAE-cellulose and adsorbed on Affi-gel blue gel and CM-Sepharose. Ganodermin inhibited the mycelial growth of Botrytis cinerea, Fusarium oxysporum and Physalospora piricola with an IC50 value of 15.2 microM, 12.4 microM and 18.1 microM, respectively. It was devoid of hemagglutinating, deoxyribonuclease, ribonuclease and protease inhibitory activities.

Amino Acid Sequence↗

PubMed2005

Secondary metabolites from Ganoderma lucidum and Spongiporus leucomallellus.

The hydrodistillates and solvent extracts of the fruit bodies of Ganoderma lucidum (Fr.) P. Karst. and Spongiporus leucomallellus (Murril) A. David were investigated. The constituents in both oils comprised hydrocarbons, monoterpenes, sesquiterpenes, and fatty acids. Major volatiles of G. lucidum were trans-anethol, R-(-)-linalool, S-(+)-carvone and alpha-bisabolol, while the essential oil of S. leucomallellus contained relatively large amounts of R-(-)-1-octene-3-ol, R-(-)-linalool, 1-hepten-3-one and (Z)-nerolidol. From the n-hexane extract of G. lucidum, the steroid ester ergosta-7,22-diene-3beta-yl pentadecanoate could be identified. From S. leucomallellus two constituents showing structures of 3,4-seco-lanostane type triterpene acids were identified as (+)-23-oxo-3,4-seco-lanosta-4(28),7(8),9(11),24(31)-tetraene-3,26-dicarboxylic acid and (+)-20-hydroxy-23-oxo-3,4-seco-lanosta-4(28),7(8),9(11),24(31)-tetraene3,26-dicarboxylic acid, respectively. Cytotoxicity and antimicrobial activity of selected compounds were investigated using standard tests.

Anti-Bacterial Agents↗