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At least 19 recordsLinked to original sources
PubMed2006

Reishi polysaccharides induce immunoglobulin production through the TLR4/TLR2-mediated induction of transcription factor Blimp-1.

The polysaccharides of Ganoderma lucidum (Reishi) possess immunomodulation activities; however, their mode of molecular action in regulating each cellular subset in the immune system is still not clear. Here, we investigate the function of the main polysaccharide fraction of Reishi (Reishi-F3) in B lymphocyte activation/differentiation. We find that Reishi-F3 causes mouse splenic B cell activation and differentiation to IgM-secreting plasma cells, and the process depends on Reishi-F3-mediated induction of Blimp-1, a master regulator capable of triggering the changes of a cascade of gene expression during plasmacytic differentiation. In human peripheral B lymphocytes, although Reishi-F3 fails to induce their activation, it is able to enhance antibody secretion, which is associated with Blimp-1 mRNA induction. The function of Reishi-F3 depends on the Toll-like receptors TLR4/TLR2 as neutralizing antibodies against TLR4/TLR2 block Reishi-F3-mediated induction of Blimp-1 mRNA and Ig secretion. We have shown that interaction of Reishi-F3 with TLR4/TLR2 followed by signaling through p38 MAPK is involved in the induction of Blimp-1 mRNA, whereas signaling through ERK, p38 MAPK, JNK, and IKK complex is involved in Reishi-F3-mediated Ig secretion. Furthermore, the differential mechanism of Reishi-F3 in mouse and human B cell activation is probably due to the presence of Blimp-1 regulatory site in human CD86 promoter. These results establish the signaling and molecular mechanisms of Reishi-F3 on promoting antibody secretion.

Animals↗
PubMed2004

Studies on the immuno-modulating and anti-tumor activities of Ganoderma lucidum (Reishi) polysaccharides.

We describe here the isolation of Reishi polysaccharides for the study of their effect on cytokine expression in mouse splenocytes. A fraction (F3) has been shown to activate the expression of IL-1, IL-6, IL-12, IFN-gamma, TNF-alpha, GM-CSF, G-CSF, and M-CSF, and from this three subfractions have been prepared where F3G1 activates IL-1, IL-12, TNF-alpha, and G-CSF, F3G2 activates all the cytokines as F3 does, and F3G3 activates only IL-1 and TNF-alpha. Together with previous studies, the mode of action on macrophages has been proposed where F3 binds to TLR4 receptor and activates extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK) and p38 to induce IL-1 expression.

Animals↗
PubMed2003

Ganoderma lucidum (Reishi) in cancer treatment.

The popular edible mushroom Ganoderma lucidum (Reishi) has been widely used for the general promotion of health and longevity in Asian countries. The dried powder of Ganoderma lucidum was popular as a cancer chemotherapy agent in ancient China. The authors recently demonstrated that Ganoderma lucidum inhibits constitutively active transcription factors nuclear factor kappa B (NF-kappaB) and AP-1, which resulted in the inhibition of expression of urokinase-type plasminogen activator (uPA) and its receptor uPAR. Ganoderma lucidum also suppressed cell adhesion and cell migration of highly invasive breast and prostate cancer cells, suggesting its potency to reduce tumor invasiveness. Thus, Ganoderma lucidum clearly demonstrates anticancer activity in experiments with cancer cells and has possible therapeutic potential as a dietary supplement for an alternative therapy for breast and prostate cancer. However, because of the availability of Ganoderma lucidum from different sources, it is advisable to test its biologic activity.

Antineoplastic Agents, Phytogenic↗
PubMed2004

Immuno-potentiating effects of the antler-shaped fruiting body of Ganoderma lucidum (Rokkaku-Reishi).

The immuno-potentiating effects of the antler-shaped fruiting body of Ganoderma lucidum (Rokkaku-Reishi, RR), which has been used as a traditional supplement for human health, were investigated in mice. BALB/c mice were administered orally with RR for 3 days at a dose of 50 mg/kg or 500 mg/kg, and interferon-gamma (IFN-gamma) production by splenocytes in response to lipopolysaccharide (LPS) was examined on day 4. The oral administration of 500 mg/kg of RR resulted in a significant increase (p<0.05) in IFN-gamma production. Stimulation of splenic adherent cells from these mice with LPS also resulted in a significant increase (p<0.05) in interleukin-12 (IL-12) production compared with that from the control mice, suggesting that splenic macrophages were activated by RR administration. Furthermore, 500 mg/kg of RR administered for 14 days resulted in a significant increase (p<0.05) in IFN-gamma production by splenocytes in response to both LPS and concanavalin A (Con A). These results suggest that not only splenic macrophages but also T cells were activated by the long-term treatment with RR in vivo. On the other hand, the production of interleukin-4 (IL-4), which is known as an allergic disease-related cytokine, was not affected by the long-term treatment with RR. Our results suggest that the oral administration of RR resulted in Th1-associated immuno-potentiating activities in vivo.

Administration, Oral↗
PubMed2004

Cellular and physiological effects of Ganoderma lucidum (Reishi).

In Asia, a variety of dietary products have been used for centuries as popular remedies to prevent or treat different diseases. A large number of herbs and extracts from medicinal mushrooms are used for the treatment of diseases. Mushrooms such as Ganoderma lucidum (Reishi), Lentinus edodes (Shiitake), Grifola frondosa (Maitake), Hericium erinaceum (Yamabushitake), and Inonotus obliquus (Chaga) have been collected and consumed in China, Korea, and Japan for centuries. Until recently, these mushrooms were largely unknown in the West and were considered 'fungi' without any nutritional value. However, most mushrooms are rich in vitamins, fiber, and amino acids and low in fat, cholesterol, and calories. These mushrooms contain a large variety of biologically active polysaccharides with immunostimulatory properties, which contribute to their anticancer effects. Furthermore, other bioactive substances, including triterpenes, proteins, lipids, cerebrosides, and phenols, have been identified and characterized in medicinal mushrooms. This review summarizes the biological effects of Ganoderma lucidum upon specific signaling molecules and pathways, which are responsible for its therapeutic effects.

Agaricales↗
PubMed2004

Extract of Reishi polysaccharides induces cytokine expression via TLR4-modulated protein kinase signaling pathways.

We have demonstrated that an extract of Ganoderma lucidum (Reishi or Ling-Zhi) polysaccharides (EORP) exerts immunomodulating activities by stimulating the expression of inflammatory cytokines from mouse spleen cells. Interestingly, via responding to LPS in genetic variation of murine macrophage HeNC2 and GG2EE cell lines, and using TLR4 Ab blockage in human blood-derived monocytic macrophages, we have found that the TLR4, but not complement receptor type 3, is a putative receptor of EORP, mediating the consequent immunomodulating events associated with IL-1 gene expression. Based on our studies of reactive oxygen species production, polymyxin B inhibition, and protein tyrosine kinase (PTK) activity, we ruled out the possibility of LPS contamination in EORP. We have found that EORP differentially modulates the protein kinase (PK)-mediated signal transduction pathways associated with inflammatory cytokine IL-1. In human macrophages and murine macrophage J774A.1 cells, EORP was found to up-regulate IL-1 secretion and pro-IL-1 (precursor of IL-1) as well as IL-1-converting enzyme expression. Specifically, EORP rapidly stimulates PTK-mediated phosphorylation, followed by induction of PKs and activation of MAPKs: ERK, JNK, and p38. Using PK inhibitors in the kinase activity assays, Western blot analyses and IL-1 ELISA, we have extensively examined and dissected the role of individual PK in the regulation of pro-IL-1/IL-1. Our findings establish that EORP-mediated signaling pathways are involved in the pro-IL-1/IL-1 regulation: PTK/protein kinase C/MEK1/ERK and PTK/Rac1/p21-activated kinase/p38.

Animals↗
PubMed2002

Studies on the immuno-modulating and antitumor activities of Ganoderma lucidum (Reishi) polysaccharides: functional and proteomic analyses of a fucose-containing glycoprotein fraction responsible for the activities.

A fucose-containing glycoprotein fraction which stimulates spleen cell proliferation and cytokine expression has been identified from the water-soluble extract of Ganoderma lucidum. Proteomic analysis of mouse spleen cells treated with this glycoprotein fraction showed approximately 50% change of the proteome. Further studies on the activities of this glycoprotein fraction through selective proteolysis and glycosidic cleavage indicate that a fucose containing polysaccharide fraction is responsible for stimulating the expression of cytokines, especially IL-1, IL-2 and INF-gamma.

Adjuvants, Immunologic↗
PubMed2005

Ganoderma lucidum inhibits inducible nitric oxide synthase expression in macrophages.

Nitric oxide (NO) is a principal mediator in many physiological and pathological processes. Overproduction of NO via the inducible nitric oxide synthase (iNOS) has cytotoxic effect through the formation of peroxynitrite with superoxide anion. The iNOS is mainly expressed in macrophages and is able to produce large amount of NO. The expression of iNOS is mainly regulated at the transcriptional level. The iNOS-mediated NO production plays a role in the development of atherosclerosis. Ganoderma lucidum (G. lucidum, Linzhi or Reishi) is a traditional herbal medicine which is commonly used as health supplement. Several studies have demonstrated its effectiveness against cancer, immunological disorders and cardiovascular diseases. The objective of the present study was to investigate the effect of G. lucidum on iNOS-mediated NO production in macrophages. Human monocytic cell (THP-1) derived macrophages were incubated with lipopolysaccharide (LPS) for 24 h. Such treatment significantly stimulated NO production (253% versus the control). Such a stimulatory effect was resulted from increased iNOS mRNA expression (270% versus the control) and iNOS activity (169.5% versus the control) in macrophages. The superoxide anion level was also elevated (150% versus the control) in LPS-treated macrophages. Treatment of macrophages with G. lucidum extract (100 microg/ml) completely abolished LPS-induced iNOS mRNA expression and NO production. Such an inhibitory effect of G. lucidum was mediated via its antioxidant action against LPS-induced superoxide anion generation in macrophages. These results suggest that G. lucidum may exert a therapeutic effect against atherosclerosis via ameliorating iNOS-mediated NO overproduction in macrophages.

Antioxidants↗
PubMed2006

Comparative studies of various ganoderma species and their different parts with regard to their antitumor and immunomodulating activities in vitro.

OBJECTIVES: Ganoderma lucidum (Lingzhi or Reishi) has been commonly suggested in East Asia as a potential candidate for prevention and treatment of different diseases, including cancer. Ganoderma extracts, in particular Ganoderma lucidum (extracts or isolated components), have previously been shown to possess antitumor activities. The present study aimed at comparing three different species of Ganoderma, wildly grown versus cultivated, as well as the different parts of the fruiting body (whole fruiting body, pileus, and stipe), with regard to their antitumor effects in human breast cancer cells and immunomodulatory activities in mouse splenic lymphocytes in vitro. METHODS: The aqueous extracts (12.5-400 microg/mL) of G. lucidum, G. sinense, and G. tsugae were examined for their antiproliferative activities in human breast cancer cell lines, MCF-7 and MDA-MB-231, as well as in normal human mammary epithelial cells (primary culture). The immunomodulatory effects of the extracts were evaluated in mouse splenic lymphocytes. The proliferative responses of the mentioned cell types were determined by MTT [3-(4,5-dimethylthiazolyl)-2,5-diphenyl-tetrazolium bromide] assay. RESULTS: The present results demonstrated that the extracts of all tested Ganoderma samples could significantly inhibit cell proliferation in human breast cancer cell lines MCF-7 and MDA-MB-231, with G. tsugae being the most potent. The extracts, however, did not exert any significant cytotoxic effect on human normal mammary epithelial cells. Within the species G. sinense, the inhibitory effects of wildly grown samples were not significantly different from those of the cultivated samples, except at 400 microg/mL. Most of the tested extracts of Ganoderma stimulated mouse splenic lymphocytes proliferation. The extracts from the stipes of the G. tsugae and wildly grown G. sinense showed much stronger inhibitory effects than the other parts of the fruiting body in both cancer cell lines, whereas the extracts from the stipes of G. lucidum and wildly grown G. sinense showed stronger immunopotentiating activities in mouse splenic lymphocytes. CONCLUSIONS: These results indicate that the aqueous extracts of these commonly available Ganoderma fruiting bodies, G. lucidum, G. sinense, and G. tsugae have antitumor activities in human breast cancer cells and immunomodulatory activities in murine lymphocytes. In addition, the present findings also suggest that the stipes of fruiting bodies of Ganoderma species should be included in the preparation of extract of these fungi in order to obtain the most comprehensive active ingredients. To the best of the authors' knowledge, this is the first detailed comparison among the different parts of the fruiting bodies of Ganoderma.

Antineoplastic Agents↗
PubMed2004

Ganoderma lucidum polysaccharide fractions accelerate healing of acetic acid-induced ulcers in rats.

The polysaccharide (PS) fractions from several medicinal herbs have been reported to have anti-ulcer effects against experimental ulcers in the rat. The water-soluble PS fractions from Ganoderma lucidum (Reishi mushroom) have been shown to inhibit indomethacin-induced gastric mucosal lesions in rats. This study aimed to investigate the effect of the PS fraction from G. lucidum on the healing of gastric ulcers induced by acetic acid in the rat and to elucidate the underlying mechanisms involved. The abdomen of rats was incised, and the stomach was treated with 10 M acetic acid (100 microL) for 1 minute, and then treated with G. lucidum PS (0.1, 0.5, or 1.0 g/kg) intragastrically, once a day for 14 consecutive days. The results indicated that the oral administration of G. lucidum PS at 0.5 and 1.0 g/kg for 2 weeks caused a significant acceleration of ulcer healing by 40.1% and 55.9%, respectively. In the mechanistic studies, additional rats were treated with 10 M acetic acid to induce acute ulcers, and then treated with G. lucidum PS (1.0 g/kg) for 3, 7, 10, or 14 days. Exposure of the rat stomach to acetic acid led to decreased mucus and increased prostaglandin levels. Treatment with G. lucidum PS at 1.0 g/kg significantly (P < .05) suppressed or restored the decreased gastric mucus levels and increased gastric prostaglandin concentrations compared with the control group. These results indicates that G. lucidum PS is an active component with healing efficacy on acetic acid-induced ulcers in the rat, which may represent a useful herbal preparation for the prevention and treatment of peptic ulcers.

Acetic Acid↗
PubMed2005

Effect of 26-oxygenosterols from Ganoderma lucidum and their activity as cholesterol synthesis inhibitors.

Ganoderma lucidum is a medicinal fungus belonging to the Polyporaceae family which has long been known in Japan as Reishi and has been used extensively in traditional Chinese medicine. We report the isolation and identification of the 26-oxygenosterols ganoderol A, ganoderol B, ganoderal A, and ganoderic acid Y and their biological effects on cholesterol synthesis in a human hepatic cell line in vitro. We also investigated the site of inhibition in the cholesterol synthesis pathway. We found that these oxygenated sterols from G. lucidum inhibited cholesterol biosynthesis via conversion of acetate or mevalonate as a precursor of cholesterol. By incorporation of 24,25-dihydro-[24,25-3H2]lanosterol and [3-3H]lathosterol in the presence of ganoderol A, we determined that the point of inhibition of cholesterol synthesis is between lanosterol and lathosterol. These results demonstrate that the lanosterol 14alpha-demethylase, which converts 24,25-dihydrolanosterol to cholesterol, can be inhibited by the 26-oxygenosterols from G. lucidum. These 26-oxygenosterols could lead to novel therapeutic agents that lower blood cholesterol.

Anticholesteremic Agents↗
PubMed2004

Ganoderma lucidum suppresses growth of breast cancer cells through the inhibition of Akt/NF-kappaB signaling.

Ganoderma lucidum (Reishi, Lingzhi) is a popular Asian mushroom that has been used for more than 2 millennia for the general promotion of health and was therefore called the "Mushroom of Immortality." Ganoderma lucidum was also used in traditional Chinese medicine to prevent or treat a variety of diseases, including cancer. We previously demonstrated that Ganoderma lucidum suppresses the invasive behavior of breast cancer cells by inhibiting the transcription factor NF-kappaB. However, the molecular mechanisms responsible for the inhibitory effects of Ganoderma lucidum on the growth of highly invasive and metastatic breast cancer cells has not been fully elucidated. Here, we show that Ganoderma lucidum inhibits proliferation of breast cancer MDA-MB-231 cells by downregulating Akt/NF-kappaB signaling. Ganoderma lucidum suppresses phosphorylation of Akt on Ser473 and downregulates the expression of Akt, which results in the inhibition of NF-kappaB activity in MDA-MB-231 cells. The biological effect of Ganoderma lucidum was demonstrated by cell cycle arrest at G0/G1, which was the result of the downregulation of expression of NF-kappaB-regulated cyclin D1, followed by the inhibition of cdk4. Our results suggest that Ganoderma lucidum inhibits the growth of MDA-MB-231 breast cancer cells by modulating Akt/NF-kappaB signaling and could have potential therapeutic use for the treatment of breast cancer.

Antineoplastic Agents, Phytogenic↗
PubMed2005

Cellular and molecular mechanisms of immuno-modulation by Ganoderma lucidum.

Ganoderma lucidum (Leyss. ex Fr.) Karst. (Lingzhi or Reishi) has been used for a long time in China to prevent and treat various human diseases. G. lucidum polysaccharides extracted from G. lucidum are one of efficacious ingredient groups of G. lucidum. A number of reports have demonstrated that G. lucidum polysaccharides modulate immune function both in vivo and in vitro. The immuno-modulating effects of G. lucidum polysaccharides were extensive, including promoting the function of antigen-presenting cells, mononuclear phygocyte system, humoral immunity, and cellular immunity. Cellular and molecular mechanisms, possible receptors involved, and triggered signaling cascades have also been studied in vitro. However, whole animal experiments are still needed to further establish the mechanism of the immuno-modulating effects by G. lucidum. Evidence-based clinical trials are also needed.

Animals↗
PubMed2006

Anti-tumor activities of the antlered form of Ganoderma lucidum in allogeneic and syngeneic tumor-bearing mice.

We investigated the anti-tumor effects of a dry powder preparation of the antlered form of Ganoderma lucidum (G. lucidum AF, rokkaku-reishi in Japanese), a variant type of G. lucidum, not only in allogeneic Sarcoma 180-bearing ddY mice, but also in syngeneic MM 46-bearing C3H/He mice. G. lucidum AF inhibited tumor growth and elongated the life span when orally administered to mice by free-feeding of a 2.5% G. lucidum AF-containing diet. It also showed anti-tumor activity in spite of post-feeding after tumor inoculation. G. lucidum AF significantly countered the depression of splenic CD8+ cells and protected the decrease in interferon-gamma (IFN-gamma) production in regional lymph nodes of MM 46-bearing mice, indicating that the anti-tumor activity of G. lucidum AF might be caused by its immunostimulating action. These results suggest that the ingestion of G. lucidum AF can be useful for the prevention and curing of cancer.

Animals↗
PubMed2006

Ameliorative effect of Ganoderma lucidum on carbon tetrachloride-induced liver fibrosis in rats.

AIM: To investigate the effects of Reishi mushroom, Ganoderma lucidum extract (GLE), on liver fibrosis induced by carbon tetrachloride (CCl4) in rats. METHODS: Rat hepatic fibrosis was induced by CCl4. Forty Wistar rats were divided randomly into 4 groups: control, CCl4, and two GLE groups. Except for rats in control group, all rats were administered orally with CCl4 (20%, 0.2 mL/100 g body weight) twice a week for 8 weeks. Rats in GLE groups were treated daily with GLE (1,600 or 600 mg/kg) via gastrogavage throughout the whole experimental period. Liver function parameters, such as ALT, AST, albumin, and albumin/globulin (A/G) ratio, spleen weight and hepatic amounts of protein, malondiladehyde (MDA) and hydroxyproline (HP) were determined. Histochemical staining of Sirius red was performed. Expression of transforming growth factor beta1 (TGF-beta1), methionine adenosyltransferase (MAT1) 1A and MAT2A mRNA were detected by using RT-PCR. RESULTS: CCl4 caused liver fibrosis, featuring increase in plasma transaminases, hepatic MDA and HP contents, and spleen weight; and decrease in plasma albumin, A/G ratio and hepatic protein level. Compared with CCl4 group, GLE (600, 1,600 mg/kg) treatment significantly increased plasma albumin level and A/G ratio (P < 0.05) and reduced the hepatic HP content (P < 0.01). GLE (1,600 mg/kg) treatment markedly decreased the activities of transaminases (P < 0.05), spleen weight (P < 0.05) and hepatic MDA content (P < 0.05); but increased hepatic protein level (P < 0.05). Liver histology in the GLE (1,600 mg/kg)-treated rats was also improved (P < 0.01). RT-PCR analysis showed that GLE treatment decreased the expression of TGF-beta1 (P < 0.05-0.001) and changed the expression of MAT1A (P < 0.05-0.01) and MAT2A (P < 0.05-0.001). CONCLUSION: Oral administration of GLE significantly reduces CCl4-induced hepatic fibrosis in rats, probably by exerting a protective effect against hepatocellular necrosis by its free-radical scavenging ability.

Animals↗
PubMed2004

Ganoderma lucidum inhibits proliferation and induces apoptosis in human prostate cancer cells PC-3.

Ganoderma lucidum (Reishi), an oriental medical mushroom, has been widely used in Asian countries for centuries to prevent or treat different diseases, including cancer. However, the mechanism(s) responsible for the effects of Ganoderma lucidum on cancer cells remain to be elucidated. We have previously demonstrated that Ganoderma lucidum down-regulated the expression of NF-kappaB-regulated urokinase plasminogen activator (uPA) and uPA receptor (uPAR), which resulted in suppression of cell migration of highly invasive human breast and prostate cancer cells. In this study, we investigated the effects of Ganoderma lucidum on cell proliferation, cell cycle, and apoptosis in human prostate cancer cells PC-3. Our data demonstrate that Ganoderma lucidum inhibits cell proliferation in a dose- and time-dependent manner by the down-regulation of expression of cyclin B and Cdc2 and by the up-regulation of p21 expression. The inhibition of cell growth was also demonstrated by cell cycle arrest at G2/M phase. Furthermore, Ganoderma lucidum induced apoptosis of PC-3 cells with a slight decrease in the expression of NF-kappaB-regulated Bcl-2 and Bcl-xl. However, the expression of proapoptotic Bax protein was markedly up-regulated, resulting in the enhancement of the ratio of Bax/Bcl-2 and Bax/Bcl-xl. Thus, Ganoderma lucidum exerts its effect on cancer cells by multiple mechanisms and may have potential therapeutic use for the prevention and treatment of cancer.

Annexin A5↗
PubMed2005

[Soothing effect of Ganoderma lucidum antlered form on cyclophosphamide-induced adverse reaction].

The immunological functions of Ganoderma lucidum antlered form (AF) (Rokkaku-Reishi in Japanese), a variant type of Ganoderma lucidum, were investigated in C57BL/6 mice treated with cyclophosphamide (CY). Ganoderma lucidum AF alleviated CY-induced decrease in body weight and abnormal increase in blood neutrophil level, when the mice were fed a diet containing 2.5% Ganoderma lucidum AF starting one week before CY treatment (150 mg/kg, ip). The recovery of CD8+ and NK1.1+ cells in the spleen was accelerated in Ganoderma lucidum AF group compared to the control group. Ganoderma lucidum AF also both alleviated CY-induced splenic lymphopenia and suppressed the abnormal increase in splenocytes 7 days after CY treatment. These results suggest that ingestion of Ganoderma lucidum AF is beneficial for improvement of quality of life reduced by anti-cancer chemotherapeutic drugs such as CY.

Administration, Oral↗
PubMed2004

The effects of bitter melon (Momordica charantia) on serum and liver triglyceride levels in rats.

Effects of three different varieties (Koimidori, Powerful-Reishi, and Hyakunari) of bitter melon (Momordica charantia) and those of methanol fraction extract of Koimidori variety on serum and liver triglycerides were studied in rats. Feeding of diets containing either bitter melon or various fractions isolated by organic solvents caused no adverse effects on food intake or growth of rats. When the effect of three different varieties of bitter melon was compared, the Koimidori variety was found to be the most effective in lowering hepatic triglyceride levels as compared to the other two varieties, suggesting a variety-dependent difference in their activity. Furthermore, the active component(s) responsible for the liver triglyceride lowering activity of Koimidori variety was assumed to be concentrated in the methanol fraction, but not in other fractions such as the n-hexane, the acetone, or the residual fraction. The triglyceride lowering activity was furthermore confirmed by the dose-dependent reduction of hepatic triglyceride, resulting the lowest level in rats fed 3.0% supplementation. In these experiments, the effects on serum lipids were marginal. The results of the present and previous studies clearly show that bitter melon, especially Koimidori variety, exhibits a potent liver triglyceride-lowering activity.

Animals↗