Ganoderma extract activates MAP kinases and induces the neuronal differentiation of rat pheochromocytoma PC12 cells.
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The pharmacology and clinical application of traditional Chinese medicine has been extensively documented. We have used an in vitro model system, PC12 cells, to demonstrate the presence of neuroactive compounds in Ganoderma lucidum (lingzhi). Ganoderma extract induced the neuronal differentiation of PC12 cells and prevented nerve growth factor-dependent PC12 neurons from apoptosis. Moreover, these effects of ganoderma might be mediated via the ras/extracellular signal-regulated kinase (Erk) and cAMP-response element binding protein (CREB) signaling pathways, as demonstrated by the phosphorylation of Erk1, Erk2 and CREB. Thus, our data not only present the first evidence of the presence of neuroactive compounds that mediate the neuronal differentiation and neuroprotection of the PC12 cells, but also reveal the potential signaling molecules involved in its action. (+info)
Structural characterization and immunomodulating activity of a complex glucan from spores of Ganoderma lucidum.
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A polysaccharide with a molecular weight of 1.26 x 10(5), obtained from the sporoderm-broken spores of Ganoderma lucidum, was purified by anion-exchange and gel-permeation chromatography. This polysaccharide had a strong effect on suppressing the antibody production and the Con A or LPS induced lymphocyte proliferation in mice. Chemically, the structure of the polysaccharide was identified by methylation analysis, 1 D, 2 D NMR and ESI-MS spectroscopic studies of the native one and of the oligosaccharide fragments generated by partial acid hydrolysis, Smith degradation, and acetolysis. It was concluded that the intact polysaccharide was a complex beta-D-glucan consisting of a (1-->6)-linked backbone chain, in which every other glucosyl residue was substituted at C-3 or C-4 with mono-, di- and trisaccharide branches. (+info)
Polysaccharide purified from Ganoderma lucidum inhibits spontaneous and Fas-mediated apoptosis in human neutrophils through activation of the phosphatidylinositol 3 kinase/Akt signaling pathway.
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Ganoderma lucidum has been widely used as a remedy to promote health and longevity in China. The polysaccharide component with a branched (1-->3)-beta-D-glucan moiety from G. lucidum (PS-G) has shown evidence of enhancement of immune responses and of eliciting anti-tumor effects. In this study, we investigated the effect of PS-G on neutrophil viability, which is manifested by spontaneous apoptosis. Annexin V staining and MTT assays reveal that PS-G is able to inhibit spontaneous and Fas-induced neutrophil apoptosis, and this effect of PS-G is enhanced by the presence of zVAD (a caspase inhibitor) and GM-CSF. The antiapoptotic effect of PS-G is diminished by the presence of wortmannin and LY294002 (two PI-3K inhibitors), but is not altered by PD98059 (a MEK inhibitor). Western blotting indicates the stimulating effect of PS-G on Akt phosphorylation and its inhibition of procaspase 3 degradation, which occurs in neutrophils undergoing spontaneous apoptosis or triggered death by Fas. Taken together, PS-G elicitation of antiapoptotic effects on neutrophils primarily relies on activation of Akt-regulated signaling pathways. (+info)
Hepatoprotective role of Ganoderma lucidum polysaccharide against BCG-induced immune liver injury in mice.
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AIM: To examine the effect of ganoderma lucidum polysaccharide (GLP) on the immune liver injury induced by BCG infection, and investigate the relationship between degrees of hepatic damage and NO production in mice. METHODS: Immune hepatic injury was markedly induced by BCG-pretreatment (125 mg.kg(-1), 2-week, iv) or by BCG-pretreatment plus lipopolysaccharide (LPS, 125 microg.kg(-1), 12-hour,iv) in mice in vivo. Hepatocellular damage induced by BCG-pretreated plus inflammatory cytokines mixture (CM), which was included TNF-alpha, IL-1beta, IFN-gamma and LPS in culture medium in vitro. Administration of GLP was performed by oral or incubating with culture medium at immune stimuli simultaneity. Liver damage was determined by activity of alanine aminotransferase (ALT) in serum and in hepatocytes cultured supernatant, by liver weight changes and histopathological examination. NO production in the cultured supernatant was determined by the Griess reaction. Moreover, inducible nitric oxide synthase (iNOS) protein expression was also examinated by immunohistochemical method. RESULTS: Immune hepatic injury was markedly induced by BCG or BCG plus inflammatory cytokines in BALB/c mice in vivo and in vitro. Under BCG-stimulated condition, augment of the liver weight and increase of the serum/supernatant ALT level were observed, as well as granuloma forming and inflammatory cells soakage were observed by microscopic analysis within liver tissues. Moreover, NO production was also increased by BCG or/and CM stimuli in the culture supernatant, and a lot of iNOS positive staining was observed in BCG-prestimulated hepatic sections. Application of GLP significantly mitigated hepatic tumefaction, decreased ALT enzyme release and NO production in serum/supernatant, improved the pathological changes of chronic and acute inflammation induced by BCG-stimuli in mice. Moreover, the immunohistochemical result showed that GLP inhibited iNOS protein expression in BCG-immune hepatic damage model. CONCLUSION: The present study indicates that NO participates in immune liver injury induced by Mycobacterium bovis BCG infection. The mechanisms of protective roles by GLP for BCG-induced immune liver injury may be due to influence NO production in mice. (+info)
Protective effects of Ganoderma lucidum polysaccharides peptide on injury of macrophages induced by reactive oxygen species.
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AIM: To study the protective effects of Ganoderma lucidum polysaccharides peptide (GLPP) on the mice peritoneal macrophages injured by reactive oxygen species (ROS), derived from tert-butylhydroperoxide (tBOOH) in vitro and in vivo. METHODS: Mice peritoneal macrophages were injured by ROS, derived from tBOOH. The survival rate of macrophages was measured by MTT assay, and the morphological changes of macrophages were observed under light and electron microscopes. RESULTS: GLPP (50, 100, 200 mg/kg, ip for 5 d) could inhibit the foam cell formation and necrosis of macrophages. The survival rate of macrophages was increased. GLPP (3.125, 12.5, 50, 200 mg/L) given to the cultured macrophages brought the same protective effects. Under the electron microscope it was found that GLPP (100 mg/kg, ip, for 5 d) could protect the organelle such as mitochondria against injury by tBOOH. CONCLUSION: GLPP had significant scavenging ROS and antioxidant effects. (+info)
Isoflavone aglycon produced by culture of soybean extracts with basidiomycetes and its anti-angiogenic activity.
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Soybean extracts (SBE) containing isoflavone glycosides were cultured with Ganoderma lucidum mycelia producing beta-glucosidase. The anti-angiogenic effects of the cultivated product, containing rich in genistein, named GCP (genistein combined polysaccharide), were assessed with chick chorioallantoic membranes (CAM) and a mouse dorsal air-sac model. Beta-glucosidase produced by the mycelia converted the isoflavone glycosides into aglycons. A test of volunteers showed that serum concentrations of genistein in the subjects treated with GCP (n = 4) at 3 h after administration were significantly higher than those in the subjects treated with SBE (n = 4). GCP inhibited angiogenesis in CAM, and the activity of GCP was greater than that of SBE. GCP inhibited the formation of new vessels induced by colon carcinoma cells in vivo. (+info)
Regulatory effect of Ganoderma lucidum polysaccharides on cytotoxic T-lymphocytes induced by dendritic cells in vitro.
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AIM: To study the regulatory effects of Ganoderma lucidum polysaccharides (Gl-PS) on cytotoxicity and mechanism of specific cytotoxic T-lymphocytes (CTL) induced by dendritic cells (DC) in vitro during the stage of antigen presentation. METHODS: Cultured murine bone marrow-derived DC were pulsed with P815 tumor cell lysates and co-incubated with or without various concentrations of Gl-PS (0.8, 3.2, or 12.8 mg/L) at the same time. P815 specific CTL were induced by spleen lymphocytes stimulated with mature DC. Non-adherent cells and culture supernatants were harvested on d 5 for analysis of specific cytotoxicity with lactate dehydrogenase (LDH) activity assay, mRNA expression of IFNgamma, granzyme B with RT-PCR assay, and protein expression of IFNgamma, granzyme B with ELISA or Western blot assay, respectively. RESULTS: Three concentrations of Gl-PS promoted LDH activities released into culture supernatants (P<0.01). It also increased mRNA expression of IFNgamma in CTL (Gl-PS 12.8 mg/L vs RPMI medium 1640, P<0.05) and granzyme B in CTL (P<0.01). Protein production of IFNgamma in culture supernatants (P<0.05) and protein expression of granzyme B in CTL (Gl-PS 12.8 mg/L vs RPMI medium 1640, P<0.05) were also augmented by Gl-PS. CONCLUSION: Gl-PS is shown to promote the cytotoxicity of specific CTL induced by DC which were pulsed with P815 tumor antigen during the stage of antigen presentation, and the mechanism of cytotoxicity is believed to be going through IFNgamma and granzyme B pathways. (+info)
Signaling mechanisms of enhanced neutrophil phagocytosis and chemotaxis by the polysaccharide purified from Ganoderma lucidum.
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1 The polysaccharide from Ganoderma lucidum (PS-G) has been reported to enhance immune responses and to elicit antitumor effects. In our previous study, we found that PS-G efficiently inhibited spontaneously and Fas-enhanced neutrophil apoptosis when cultured in vitro. Since phagocytosis and chemotaxis play essential roles in host defense mediated by neutrophils, it is of great interest to know the effect of PS-G on these two cell functions, and the molecular events leading to these actions. 2 Using latex beads and heat-inactive Escherichia coli serving as particles for neutrophil engulfment, we found that PS-G is able to enhance phagocytic activity of human primary neutrophils and neutrophilic-phenotype cells differentiated from all trans retinoic acid-treated HL-60 cells. 3 Chemotactic assay using Boyden chamber also revealed the ability of PS-G to increase neutrophil migration. 4 Exposure of neutrophils to PS-G time dependently caused increases in protein kinase C (PKC), p38 mitogen-activated protein kinase (MAPK), Hck, and Lyn activities. 5 Results with specific kinase inhibitors indicate that phagocytic action of PS-G was reduced by the presence of wortmannin (Phosphatidylinositol 3-kinase, PI3K inhibitor), pyrazolpyrimidine 2 (Src-family tyrosine kinase inhibitor), Ro318220 (PKC inhibitor), and SB203580 (p38 MAPK inhibitor), but not by PD98059 (mitogen-activated protein/ERK kinase inhibitor). Moreover, chemotactic action of PS-G requires the activities of PI3K, p38 MAPK, Src tyrosine kinases and PKC. 6 All these results demonstrate the abilities of PS-G to enhance neutrophil function in phagocytosis and chemotaxis, and further provide evidence to strengthen the beneficial remedy of G. lucidum in human to enhance defense system. (+info)