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Le Reishi, étudié cliniquement

Le Reishi rouge (Ganoderma Lucidum) est utilisé de façon ancestrale par la Médecine Traditionnelle Chinoise.

La « Mycothérapie » a ses racines dans la médecine traditionnelle orientale.

Le reishi jouit, depuis plus de 2000 ans, d’une renommée peu commune en Asie.

Il en est fait mention dans le plus vieil écrit de la pharmacopée chinoise (l’herbier classique de Seng Nong-publié en56 avant notre ère) et on croit que les Asiatiques le connaissaient depuis des siècles, voire des millénaires avant cette date.

La Médecine traditionnelle chinoise (MTC) et, à sa suite, la médecine kempo du Japon, tiennent la chair de ce champignon pour un précieux tonique du Tchi, l’énergie vitale qui soutient l’ensemble de l’organisme et l’aide à maintenir un état optimal de santé et d’équilibre.

En médecine traditionnelle, on utilise uniquement la chair du champignon (chapeau et pied) pour sa puissance  (chair du caprophore, fruit) : polysaccharides, bêta glucanes, triterpènes et protéines.

reishi - NUTRANAT

Les filaments plus ou moins ramifiés issus de la germination des spores: le mycélium (tel un réseau de connections qui peut faire écho au réseau neuronal et/ou vasculaire humain, apporte une dimension informationnelle supplémentairement à la synergie des parties de ce champignon dit de la longévité.

 Les polysaccharides ont été largement étudiés pour leurs propriétés immunostimulantes. Au sein de ce groupe, il convient de distinguer les bêta-glucanes, un groupe de polysaccharides présent dans le reishi, le maitake, qui au vu des études se revelent bien stimuler les mécanismes généraux de défense.

Les bons nutriments, en agissant comme modificateurs de la réponse biologique peuvent donc augmenter l’activation, la prolifération ou la cytotoxicité des lymphocytes NK pré-existants, mais de façon plus large, ils modulent l’immunité tout en la stimulant

Les actifs de mycothérapie ancéstrale sont aujourd’hui validés par des études cliniques plus récentes.

Un nombre impressionnant d’études cliniques ont été menées.

Tant dans le domaine infectieux, qu’allergique, les propriétés anticancéreuses pour lesquelles il est renommé de façon ancestrale ont été longuement étudiées, ainsi que son impact sur la modulation et simultanément la stimulation du système immunitaire.

Nombreuses études pour aller plus loin

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2724636/

Anal Bioanal Chem. 2009 Sep; 395(1): 37–45.

Published online 2009 May 20. doi:  10.1007/s00216-009-2838-1

PMCID: PMC2724636

Immunomodulation by food: promising concept for mitigating allergic disease?Harry Wichers

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1160565/

Mediators Inflamm. 2005 Jun 9; 2005(2): 63–80.

doi:  10.1155/MI.2005.63

PMCID: PMC1160565

Antiinflammatory and Immunomodulating Properties of Fungal Metabolites

Cristina Lull,1 Harry J. Wichers,1 and Huub F. J. Savelkoul2,*

 http://www.ncbi.nlm.nih.gov/pubmed/21213395

Am J Chin Med. 2011;39(1):15-27.

Ganoderma lucidum polysaccharides: immunomodulation and potential anti-tumor activities.

Xu Z1, Chen X, Zhong Z, Chen L, Wang Y.

Author information

Abstract

Ganoderma lucidum (G. lucidum), a basidiomycete white rot fungus, has long been prescribed to prevent and treat various human diseases, particularly in China, Japan, and Korea. Several classes of bioactive substances have been isolated and identified from G. lucidum, such as triterpenoids, polysaccharides, nucleosides, sterols, and alkaloids, among others. This paper examines the potential role of G. lucidum polysaccharide (GLPS) in tumor therapy and the possible mechanisms involved. Both in vitro and in vivo studies suggested that the anti-tumor activities of GLPS are mediated by its immunomodulatory, anti-angiogenic, and cytotoxic effects. GLPS affects immune cells and immune-related cells including B lymphocytes, T lymphocytes, dendritic cells, macrophages, and natural killer cells. In addition, recent data also suggest that GLPS suppresses tumorigenesis or inhibits tumor growth through direct cytotoxic effect and anti-angiogenic actions. However, many questions still need to be answered before both G. lucidum and GLPS can be widely accepted and used as anti-tumor agents.

PMID : 21213395 [PubMed – indexed for MEDLINE] 

http://www.ncbi.nlm.nih.gov/pubmed/15525457

Abstract http://www.ncbi.nlm.nih.gov/pubmed/15525457

Acta Pharmacol Sin. 2004 Nov;25(11):1387-95.

Anti-tumor and immunoregulatory activities of Ganoderma lucidum and its possible mechanisms.

Lin ZB1, Zhang HN.

Author information

Abstract

Ganoderma lucidum (G lucidum) is a medicinal fungus with a variety of biological activities. It has long been used as a folk remedy for promotion of health and longevity in China and other oriental countries. The most attractive character of this kind of medicinal fungus is its immunomodulatory and anti-tumor activities. Large numbers of studies have shown that G lucidum modulate many components of the immune system such as the antigen-presenting cells, NK cells, T and B lymphocytes. The water extract and the polysaccharides fraction of G lucidum exhibited significant anti-tumor effect in several tumor-bearing animals mainly through its immunoenhancing activity. Recent studies also showed that the alcohol extract or the triterpene fraction of G lucidum possessed anti-tumor effect, which seemed to be related to the cytotoxic activity against tumor cells directly. Preliminary study indicated that antiangiogenic effect may be involved antitumor activity of G lucidum.

PMID : 15525457 [PubMed – indexed for MEDLINE]

Neural Regen Res. 2014 Aug 1;9(15):1446-52. doi: 10.4103/1673-5374.139461.

Neuroprotective effect of pretreatment with ganoderma lucidum in cerebral ischemia/reperfusion injury in rat hippocampus.

Zhang W1, Zhang Q2, Deng W2, Li Y2, Xing G2, Shi X2, Du Y3.

Author information

Abstract

Ganoderma lucidum is a traditional Chinese medicine, which has been shown to have both anti-oxidative and anti-inflammatory effects, and noticeably decreases both the infarct area and neuronal apoptosis of the ischemic cortex. This study aimed to investigate the protective effects and mechanisms of pretreatment with ganoderma lucidum (by intragastric administration) in cerebral ischemia/reperfusion injury in rats. Our results showed that pretreatment with ganoderma lucidum for 3 and 7 days reduced neuronal loss in the hippocampus, diminished the content of malondialdehyde in the hippocampus and serum, decreased the levels of tumor necrosis factor-α and interleukin-8 in the hippocampus, and increased the activity of superoxide dismutase in the hippocampus and serum. These results suggest that pretreatment with ganoderma lucidum was protective against cerebral ischemia/reperfusion injury through its anti-oxidative and anti-inflammatory actions.

KEYWORDS:

anti-inflammatory; anti-oxidative; apoptosis; cerebral ischemia/reperfusion; ganoderma lucidum; hippocampus; interleukin-8; malondialdehyde; nerve regeneration; neural regeneration; superoxide dismutase; tumor necrosis factor-α

PMID : 25317156 [PubMed]

PMCID : PMC4192946

Free PMC Article

http://www.ncbi.nlm.nih.gov/pubmed/25317156

J Transl Med. 2015 Mar 26;13:100. doi: 10.1186/s12967-015-0465-5.

Ganoderma lucidum polysaccharide extract inhibits hepatocellular carcinoma growth by downregulating regulatory T cells accumulation and function by inducing microRNA-125b.

Li A1,2, Shuai X3, Jia Z4, Li H5, Liang X6, Su D7,8,9, Guo W10.

Author information

Abstract

BACKGROUND:

Ganoderma lucidum polysaccharides (GLPS) have been used as traditional Chinese medicine for their properties of cancer prevention and immunomodulation. However, it is unclear whether GLPS has therapeutic effect on anti-hepatocellular carcinoma (HCC) in vivo. In this study, the effect of GLPS and their impact on the balance of regulatory T cell (Treg) and effector T cell (Teff) was measured in a model of hepatoma-bearing mice.

METHODS:

The effect of GLPS and their impact on the balance of regulatory T cell (Treg) and effector T cell (Teff) were measured in a model of hepatoma-bearing mice. Real-time PCR detected the levels of MicroRNAs (miRNAs) and mRNA. The effects of Tregs on Teff proliferation were determined via suppression assay. The mircroRNA-125b (miR-125b) inhibitor was used to down-regulate miR-125b expression.

RESULTS:

GLPS significantly suppressed tumor growth in hepatoma-bearing mice associated with an increase of the ratio of Teffs to Tregs. Moreover, GLPS eliminate Treg suppression of Teff proliferation with an increase in IL-2 secretion. Addition of GLPS to treat T cells inhibited Notch1 and FoxP3 expression through increase of miR-125b expression. In hepatoma-bearing mice, miR-125b inhibitor obviously abolished the effect of GLPS on tumor growth.

CONCLUSIONS:

This finding provides the novel evidence for GLPS on inhibition of HCC through miR-125b inhibiting Tregs accumulation and function.

PMID : 25889022 [PubMed – in process]

PMCID : PMC4379953

Free PMC Article

http://www.ncbi.nlm.nih.gov/pubmed/25889022

Am J Chin Med. 2011;39(1):15-27.

Ganoderma lucidum polysaccharides: immunomodulation and potential anti-tumor activities.

Xu Z1, Chen X, Zhong Z, Chen L, Wang Y.

Author information

Abstract

Ganoderma lucidum (G. lucidum), a basidiomycete white rot fungus, has long been prescribed to prevent and treat various human diseases, particularly in China, Japan, and Korea. Several classes of bioactive substances have been isolated and identified from G. lucidum, such as triterpenoids, polysaccharides, nucleosides, sterols, and alkaloids, among others. This paper examines the potential role of G. lucidum polysaccharide (GLPS) in tumor therapy and the possible mechanisms involved. Both in vitro and in vivo studies suggested that the anti-tumor activities of GLPS are mediated by its immunomodulatory, anti-angiogenic, and cytotoxic effects. GLPS affects immune cells and immune-related cells including B lymphocytes, T lymphocytes, dendritic cells, macrophages, and natural killer cells. In addition, recent data also suggest that GLPS suppresses tumorigenesis or inhibits tumor growth through direct cytotoxic effect and anti-angiogenic actions. However, many questions still need to be answered before both G. lucidum and GLPS can be widely accepted and used as anti-tumor agents.

PMID : 21213395 [PubMed – indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov/pubmed/21213395

Curr Pharm Biotechnol. 2009 Dec;10(8):717-42.

Ganoderma lucidum: a potent pharmacological macrofungus.

Sanodiya BS1, Thakur GS, Baghel RK, Prasad GB, Bisen PS.

Author information

Abstract

Ganoderma lucidum (Ling Zhi) is a basidiomycete white rot macrofungus which has been used extensively as « the mushroom of immortality » in China, Japan, Korea and other Asian countries for 2000 years. A great deal of work has been carried out on therapeutic potential of Ganoderma lucidum. The basidiocarp, mycelia and spores of Ganoderma lucidum contain approximately 400 different bioactive compounds, which mainly include triterpenoids, polysaccharides, nucleotides, sterols, steroids, fatty acids, proteins/peptides and trace elements which has been reported to have a number of pharmacological effects including immunomodulation, anti-atherosclerotic, anti-inflammatory, analgesic, chemo-preventive, antitumor, chemo and radio protective, sleep promoting, antibacterial, antiviral (including anti-HIV), hypolipidemic, anti-fibrotic, hepatoprotective, anti-diabetic, anti-androgenic, anti-angiogenic, anti-herpetic, antioxidative and radical-scavenging, anti-aging, hypoglycemic, estrogenic activity and anti-ulcer properties. Ganoderma lucidum has now become recognized as an alternative adjuvant in the treatment of leukemia, carcinoma, hepatitis and diabetes. The macrofungus is very rare in nature rather not sufficient for commercial exploitation for vital therapeutic emergencies, therefore, the cultivation on solid substrates, stationary liquid medium or by submerged cultivation has become an essential aspect to meet the driving force towards the increasing demands in the international market. Present review focuses on the pharmacological aspects, cultivation methods and bioactive metabolites playing a significant role in various therapeutic applications.

PMID : 19939212 [PubMed – indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov/pubmed/19939212

Biotechnol Annu Rev. 2007;13:265-301.

Ganoderma lucidum and its pharmaceutically active compounds.

Boh B1, Berovic M, Zhang J, Zhi-Bin L.

Author information

Abstract

Ganoderma lucidum is a wood-degrading basidiomycete with numerous pharmacological effects. Since the mushroom is very rare in nature, artificial cultivation of fruiting bodies has been known on wood logs and on sawdust in plastic bags or bottles. Biotechnological cultivation of G. lucidum mycelia in bioreactors has also been established, both on solid substrates and in liquid media by submerged cultivation of fungal biomass. The most important pharmacologically active constituents of G. lucidum are triterpenoids and polysaccharides. Triterpenoids have been reported to possess hepatoprotective, anti-hypertensive, hypocholesterolemic and anti-histaminic effects, anti-tumor and anti-engiogenic activity, effects on platelet aggregation and complement inhibition. Polysaccharides, especially beta-d-glucans, have been known to possess anti-tumor effects through immunomodulation and anti-angiogenesis. In addition, polysaccharides have a protective effect against free radicals and reduce cell damage caused by mutagens.

PMID : 17875480 [PubMed – indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov/pubmed/17875480

Int J Mol Med. 2011 Dec;28(6):1065-9. doi: 10.3892/ijmm.2011.788. Epub 2011 Sep 1.

Suppression of proliferation and oxidative stress by extracts of Ganoderma lucidum in the ovarian cancer cell line OVCAR-3.

Hsieh TC1, Wu JM.

Author information

Abstract

Lingzhi (LZ) is a medical mushroom also known as Ganoderma lucidum, which has been used in traditional Chinese medicine for more than 4,000 years and moreover, due to its presumed health benefits and apparent absence of side-effects it has also been widely consumed as a dietary supplement by cancer patients and by individuals diagnosed with various chronic diseases. The reported benefits of Ganoderma lucidum may be largely ascribed to its biologically active constituent polysaccharides and triterpenes known as ganoderic acids having structural similarity to steroid hormones. Laboratory studies have shown that Ganoderma lucidum enhances immune functions and also inhibits growth of various cancer cells both in vitro and in vivo. However, the mechanism by which Ganoderma lucidum exerts its chemopreventive activities remains unknown. In this study, we investigated whether Ganoderma lucidum elicits its anti-tumor effects by suppressing cell growth and inducing antioxidative/detoxification activity in human ovarian OVCAR-3 cells. The results showed that Ganoderma lucidum inhibits cell growth and disruption of cell cycle progression via down regulation of cyclin D1. Chemopreventive activities elicited by Ganoderma lucidum were demonstrated by the induction of antioxidant SOD and catalase as well as the phase II detoxification enzyme NAD(P)H:quinone oxidoreductase 1 (NQO1) and glutathione S-transferase P1 (GSTP1) via the Nrf2 mediated signaling pathway known to provide chemoprotection against carcinogenicity. These findings indicate that Ganoderma lucidum possesses chemopreventive potential contributing to its overall health effects and further suggest that Ganoderma lucidum may have clinical applications as an adjunct supplementary agent in chemotherapy.

PMID : 21887458 [PubMed – indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov/pubmed/21887458

BMC Complement Altern Med. 2014 Nov 5;14:434. doi: 10.1186/1472-6882-14-434.

Ganoderma lucidum inhibits proliferation of human ovarian cancer cells by suppressing VEGF expression and up-regulating the expression of connexin 43.

Dai S1, Liu J, Sun X, Wang N.

Author information

Abstract

BACKGROUND:

Ganoderma lucidum (G. lucidum, Reishimax) is an herbal mushroom known to have inhibitory effect on tumor cell growth. However, the molecular mechanisms responsible for its anti-proliferative effects on the ovarian cancer have not been fully elucidated.

METHODS:

Human ovarian cancer cells HO 8910 (HOCC) and human primary ovarian cells (HPOC) were treated with G. lucidum. Effects of G. lucidum treatment on cell proliferation were studied by MTT assay. The expression of vascular endothelial growth factor (VEGF) and connexin 43 (Cx43) were measured by immunohistochemistry and real time polymerase chain reaction. To study the molecular mechanism of CX43 mediated anti-tumor activity, small interference RNA (siRNA) was used to knockdown Cx43 expression in HOCC.

RESULTS:

  • lucidum treatment resulted in reduced proliferation of HOCC. Inhibition of proliferation was accompanied by a decrease in VEGF expression and increase in Cx43 expression in the cancer cells. The extent of immune-reactivity of Cx43 or VEGF in cancer cells were correlated with the concentrations of G. lucidum used for treatment. Furthermore, knockdown of Cx43 expression in HOCC abrogated the effect of G. lucidum on cell proliferation without alteration of G. lucidum-induced attenuation of VEGF expression.

CONCLUSIONS:

  • lucidum inhibits ovarian cancer by down-regulating the expression of VEGF and up-regulating the downstream Cx43 expression. G. lucidum may be a promising therapeutic agent for the treatment of ovarian cancer.

PMID : 25374251 [PubMed – indexed for MEDLINE]

PMCID : PMC4232730

Free PMC Article

http://www.ncbi.nlm.nih.gov/pubmed/25374251

Nutr Cancer. 2004;49(2):209-16.

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

Jiang J1, Slivova V, Harvey K, Valachovicova T, Sliva D.

Author information

Abstract

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.

http://www.ncbi.nlm.nih.gov/pubmed/15489214

Immunol Invest. 2005;34(2):171-98.

Antitumor activity and underlying mechanisms of ganopoly, the refined polysaccharides extracted from Ganoderma lucidum, in mice.

Gao Y1, Gao H, Chan E, Tang W, Xu A, Yang H, Huang M, Lan J, Li X, Duan W, Xu C, Zhou S.

Author information

Abstract

Ganopoly is an aqueous polysaccharide fraction extracted from G. lucidum by patented biochemical technique and has been marketed as an over-the-counter product for chronic diseases including cancer and hepatopathy in many Asian countries. This study was undertaken to explore the anti-tumour effect and the underlying mechanisms of Ganopoly in mice and human tumor cell lines. The maximum tolerated dose (MTD) of Ganopoly in mice was estimated to be 100 mg/kg from a pilot study. Treatment of mice with oral Ganopoly for 10 days significantly reduced the tumour weight of sarcoma-180 in a dose-dependent manner, with inhibition rates of 32.3, 48.2 and 84.9% and growth delays of 1.5, 3.5, and 13.1 days at 20, 50, and 100 mg/kg, respectively. Incubation of Ganopoly at 0.05-1.0 mg/ml for 48 hours showed little or negligible cytotoxicity against human tumor CaSki, SiHa, Hep3B, HepG2, HCT116 HT29, and MCF7 cells in vitro. In contrast, 10 mg/ml of Ganopoly caused significant cytotoxicity in all tumour cells tested except MCF7, with marked apoptotic effect observed in CaSki, HepG2, and HCT116 cells, as indicated by nuclear staining and DNA fragmentation. In addition, Ganopoly enhanced concanavalin A-stimulated proliferation of murine splenocytes by 35.3% at 10 mg/ml, and stimulated the production of nitric oxide in thioglycollate-primed murine peritoneal macrophages in a concentration-dependent manner over 0.05-10 mg/ml. Addition of Ganopoly at 1 mg/ ml to murine peritoneal macrophages also potentiated lipopolysaccharide-induced nitric oxide production by 64.2%. Treatment of healthy mice or mice bearing sarsoma-180 with oral Ganopoly over 20-100 mg/kg for 7 day significantly increased the expression of both TNF-alpha and IFN-gamma (at both mRNA and protein levels) in splenocytes in a dose-dependent manner. Moreover, treatment of Ganopoly over 20-100 mg/kg significantly increased cytotoxic T lymphocyte cytotoxicity and NK activity in mice. The overall findings indicated that Ganopoly had antitumor activity with a broad spectrum of immuno-modulating activities and may represent a novel promising immunotherapeutic agent in cancer treatment.

http://www.ncbi.nlm.nih.gov/pubmed/15921158

J Med Food. 2005 Summer;8(2):159-68.

Effects of water-soluble Ganoderma lucidum polysaccharides on the immune functions of patients with advanced lung cancer.

Gao Y1, Tang W, Dai X, Gao H, Chen G, Ye J, Chan E, Koh HL, Li X, Zhou S.

Author information

Abstract

Preclinical studies have established that the polysaccharide fractions of Ganoderma lucidum have potential antitumor activity. Recent clinical studies have demonstrated that G. lucidum polysaccharides enhance host immune functions [e.g., enhanced natural killer (NK) cell activity] in patients with advanced solid tumors, although an objective response was not observed. This open-label study aimed to evaluate the effects of water-soluble G. lucidum polysaccharides (Ganopoly, Encore International Corp., Auckland, New Zealand) on immune functions in patients with advanced lung cancer. Thirty-six patients were enrolled and treated with 5.4 g/day Ganopoly for 12 weeks. In the 30 cancer patients who completed the trial, treatment with Ganopoly did not significantly alter the mean mitogenic reactivity to phytohemagglutinin, mean counts of CD3, CD4, CD8, and CD56, mean plasma concentrations of interleukin (IL)-2, IL-6, and interferon (IFN)-gamma, or NK activity in the patients, but the results were significantly variable. However, some cancer patients demonstrated markedly modulated immune functions. The changes in IL-1 were correlated with those for IL-6, IFN-gamma, CD3, CD8, and NK activity (P < .05), and IL-2 changes were correlated with those for IL-6, CD8, and NK activity. The results suggest that subgroups of cancer patients might be responsive to Ganopoly in combination with chemotherapy/radiotherapy. Further studies are needed to explore the efficacy and safety of Ganopoly used alone or in combination with chemotherapy/radiotherapy in lung cancer patients.

PMID : 16117607 [PubMed – indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov/pubmed/16117607

Immunol Invest. 2003 Aug;32(3):201-15.

Effects of ganopoly (a Ganoderma lucidum polysaccharide extract) on the immune functions in advanced-stage cancer patients.

Gao Y1, Zhou S, Jiang W, Huang M, Dai X.

Author information

Abstract

Preclinical studies have established that the Ganoderma lucidum polysaccharide (GLPS) fractions have potent anti-tumor activity, which has been associated with the immuno-stimulating effects of GLPS. However, it is unclear whether GLPS has immuno-modulating effects in humans in vivo. This study aimed to investigate the effects of Ganopoly, the polysaccharides fractions extracted from G. lucidum, on the immune function of advanced-stage cancer patients. Thirty-four advance-stage cancer patients were entered onto this study, and treated with 1800 mg Ganopoly, three times daily orally before meals for 12 weeks. Immune parameters (cytokines, T cell subsets, mitotic response to phytohemagglutinin (PHA) and natural killer activity) were compared between baseline and after 12-week treatment. Thirty patients are assessable for their immune functions. Treatment of Ganopoly for 12 weeks resulted in a significant (P < 0.05) increase in the mean plasma concentrations of interleukin (IL-2), IL-6, and interferon (IFN)-gamma, whereas the levels of IL-1 and tumor necrosis factor (TNF-alpha) were significantly (P < 0.05) decreased. A marked variability among patients with advanced-stage cancer was observed in the numbers of each lymphocyte subset at baseline. The mean absolute number of CD56+ cells was significantly (P < 0.05) increased after 12-week treatment of Ganopoly, whereas the numbers of CD3+, CD4+, and CD8+ were just marginally increased compared to baseline levels, with the CD4:CD8 T cell ratios unchanged. PHA responses after 12-week treatment with Ganopoly were enhanced in most patients, when compared to pretreatment baselines (P < 0.05). In addition, Ganopoly treatment resulted in a significant increase (P < 0.05) in the mean NK activity compared to baselines (34.5 +/- 11.8% vs 26.6 +/- 8.3%). The present study indicates that Ganopoly enhanced the immune responses in patients with advanced-stage cancer. Clinical evaluations of response and toxicity are ongoing.

PMID : 12916709 [PubMed – indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov/pubmed/12916709

Acta Pharmacol Sin. 2004 Nov;25(11):1387-95.

Anti-tumor and immunoregulatory activities of Ganoderma lucidum and its possible mechanisms.

Lin ZB1, Zhang HN.

Author information

Abstract

Ganoderma lucidum (G lucidum) is a medicinal fungus with a variety of biological activities. It has long been used as a folk remedy for promotion of health and longevity in China and other oriental countries. The most attractive character of this kind of medicinal fungus is its immunomodulatory and anti-tumor activities. Large numbers of studies have shown that G lucidum modulate many components of the immune system such as the antigen-presenting cells, NK cells, T and B lymphocytes. The water extract and the polysaccharides fraction of G lucidum exhibited significant anti-tumor effect in several tumor-bearing animals mainly through its immunoenhancing activity. Recent studies also showed that the alcohol extract or the triterpene fraction of G lucidum possessed anti-tumor effect, which seemed to be related to the cytotoxic activity against tumor cells directly. Preliminary study indicated that antiangiogenic effect may be involved antitumor activity of G lucidum.

PMID : 15525457 [PubMed – indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov/pubmed/15525457

Carbohydrates

Polysaccharides are the best known and most potent mushroom derived substances with antitumor and immunomodulating properties. Data on mushroom polysaccharides have been collected from hundreds of different species of higher basidiomycetes; some specific carbohydrates with these properties have been quantified in different mushrooms: rhamnose, xylose, fucose, arabinose, fructose, glucose, mannose, mannitol, sucrose, maltose, and trehalose (Table 2) [11, 15, 38, 39].

Composition of sugars of some edible mushrooms (dry weight).

The antitumor polysaccharides isolated from mushrooms are acidic or neutral, with strong antitumor action and differ significantly in their chemical structures. A wide range of glycans extending from homopolymers to highly complex heteropolymers exhibits antitumoral activity. Mushroom polysaccharides have antitumor action by activation of the immune response of the host organism, in other words, mushroom polysaccharides do not directly kill tumor cells. These compounds prevent stress on the body and they may produce around 50% reduction in tumor size and prolong the survival time of tumor bearing mice [39, 40].

β-glucans are the main polysaccharides found in mushrooms and around half of the fungal cell wall mass is constituted by β-glucans. This is important for the industry because many of them are excreted into the cell growth medium, making their recovery, purification and chemical characterization very simple [4143]. β-glucans are responsible for anticancer, immunomodulating, anticholesterolemic, antioxidant, and neuroprotective activities of many edible mushrooms. Also, they are recognized as potent immunological stimulators in humans, and it has been demonstrated their capacity for treating several diseases. β-glucans bind to a membrane receptor and induce these biological responses [4447].

Natural products with fungal β-glucans have been consumed for thousands of years and they have long been considered to improve general health [48]. β-glucans are not synthesized by humans and they are not recognized by human immune systems as self-molecules; as a result they induce both innate and adaptive immune responses [49]. Fungal β-glucans are notably beneficial to humans; they markedly stimulate the human immune system and protect from pathogenic microbes and from harmful effects of environmental toxins and carcinogens that impaired immune systems. They also protect from infectious diseases and cancer and aid patients recovery from chemotherapy and radiotherapy. Besides, these compounds are also beneficial to middle-age people, people with active and stressful lifestyles, and athletes. A large variability can be observed in mushroom species and their concentration ranges from 0.21 to 0.53 g/100 g dry basis [20, 50].

β-glucans are well known for their biological activity, specifically related to the immune system. Hence, activating and reinforcing the host immune system seem to be the best strategy for inhibiting the growth of cancer cells [17, 51].

Proteins

Bioactive proteins are an important part of functional components in mushrooms and also have great value for their pharmaceutical potential. Mushrooms produce a large number of proteins and peptides with interesting biological activities such as lectins, fungal immunomodulatory proteins, ribosome inactivating proteins, antimicrobial proteins, ribonucleases, and laccases [52].

Lectins are nonimmune proteins or glycoproteins binding specifically to cell surface carbohydrates and in the past few years many mushroom lectins have been discovered [53]. They have many pharmaceutical activities and possess immunomodulatory properties, antitumoral, antiviral, antibacterial, and antifungal activity. Some of them exhibit highly potent antiproliferative activity toward some tumor cell lines (human leukemic T cells, hepatoma Hep G2 cells, and breast cancer MCF7 cells) [52, 54].

Fungal immunomodulatory proteins are a new family of bioactive proteins isolated from mushrooms, which have shown a potential application as adjuvants for tumor immunotherapy mainly due to their activity in suppressing tumor invasion and metastasis [55]. Xu et al. [52] published an extensive and comprehensive review about bioactive proteins in mushrooms.

Voir http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4320875/

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Biosci Biotechnol Biochem. 2009 Dec;73(12):2589-94. Epub 2009 Dec 7.

Ganoderma lucidum extracts inhibited leukemia WEHI-3 cells in BALB/c mice and promoted an immune response in vivo.

Chang YH1, Yang JS, Yang JL, Wu CL, Chang SJ, Lu KW, Lin JJ, Hsia TC, Lin YT, Ho CC, Wood WG, Chung JG.

Author information

Abstract

Ganoderma lucidum (G. lucidum) is a medicinal mushroom having biological effects such as immunomodulation and anti-tumor actions. In China and many other Asian countries, G. lucidum is used as a folk remedy to promote health and longevity. Although many studies have shown that G. lucidum modulates the immune system, including, for example, antigen-presenting cells, natural killer (NK) cells, and the T and B lymphocytes, the effects of G. lucidum on the WEHI-3 leukemic BALB/c mice are unclear. We attempted to determine whether G. lucidum would promote immune responses in BALB/c mice injected with WEHI-3 leukemia cells. The effects of G. lucidum on the survival rate of WEHI-3 leukemia cells injected into BALB/c mice were examined. It increased the percentages of CD3 and CD19, but decreased the percentages of Mac-3 and CD11b markers, suggesting that differentiation of the precursor of T and B cells was promoted but macrophages were inhibited. It decreased the weight of spleens as compared with control mice. It also promoted phagocytosis by macrophage from peripheral blood mononuclear cell (PBMC) and it also promoted natural killer cell activity. It decreased the percentage of leukemia cells in the spleens of mice before they were injected with WEHI-3 cells. Apparently, G. lucidum affects murine leukemia WEHI-3 cells in vivo.

PMID : 19966494 [PubMed – indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov/pubmed/19966494

J Transl Med. 2015 Mar 26;13:100. doi: 10.1186/s12967-015-0465-5.

Ganoderma lucidum polysaccharide extract inhibits hepatocellular carcinoma growth by downregulating regulatory T cells accumulation and function by inducing microRNA-125b.

Li A1,2, Shuai X3, Jia Z4, Li H5, Liang X6, Su D7,8,9, Guo W10.

Author information

Abstract

BACKGROUND:

Ganoderma lucidum polysaccharides (GLPS) have been used as traditional Chinese medicine for their properties of cancer prevention and immunomodulation. However, it is unclear whether GLPS has therapeutic effect on anti-hepatocellular carcinoma (HCC) in vivo. In this study, the effect of GLPS and their impact on the balance of regulatory T cell (Treg) and effector T cell (Teff) was measured in a model of hepatoma-bearing mice.

METHODS:

The effect of GLPS and their impact on the balance of regulatory T cell (Treg) and effector T cell (Teff) were measured in a model of hepatoma-bearing mice. Real-time PCR detected the levels of MicroRNAs (miRNAs) and mRNA. The effects of Tregs on Teff proliferation were determined via suppression assay. The mircroRNA-125b (miR-125b) inhibitor was used to down-regulate miR-125b expression.

RESULTS:

GLPS significantly suppressed tumor growth in hepatoma-bearing mice associated with an increase of the ratio of Teffs to Tregs. Moreover, GLPS eliminate Treg suppression of Teff proliferation with an increase in IL-2 secretion. Addition of GLPS to treat T cells inhibited Notch1 and FoxP3 expression through increase of miR-125b expression. In hepatoma-bearing mice, miR-125b inhibitor obviously abolished the effect of GLPS on tumor growth.

CONCLUSIONS:

This finding provides the novel evidence for GLPS on inhibition of HCC through miR-125b inhibiting Tregs accumulation and function.

PMID : 25889022 [PubMed – in process]

PMCID : PMC4379953

Free PMC Article

http://www.ncbi.nlm.nih.gov/pubmed/25889022

Integr Cancer Ther. 2015 May;14(3):249-57. doi: 10.1177/1534735414568721. Epub 2015 Jan 27.

Ganoderma lucidum for cancer treatment: we are close but still not there.

Cheng S1, Sliva D2.

Author information

Abstract

The medicinal fungus Ganoderma lucidum has been used in traditional Chinese medicine for millennia to improve health and promote longevity. The idea of using G. lucidum for cancer treatment is based on numerous laboratory and preclinical studies with cancer and immune cells as well as animal models demonstrating various biological activities in vitro and in vivo. For example, G. lucidum possesses cytotoxic, cytostatic, antimetastatic, anti-inflammatory, and immunomodulating activities. Limited clinical studies, including case reports and randomized controlled trials, suggest G. lucidum as an alternative adjunct therapy for stimulating the immune system in cancer patients. To confirm the efficacy of G. lucidum in cancer treatment, systematic translational research programs should be started worldwide. In addition, only standardized preclinically evaluated, biologically active G. lucidum extracts should be used in alternative treatments. This approach will lead to the development of standardized G. lucidum preparations with specific chemical fingerprint-associated anticancer activities.

© The Author(s) 2015.

http://www.ncbi.nlm.nih.gov/pubmed/25626896

J Altern Complement Med. 2006 Oct;12(8):777-89.

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

Yue GG1, Fung KP, Tse GM, Leung PC, Lau CB.

Author information

Abstract

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.

PMID : 17034284 [PubMed – indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov/pubmed/17034284

Biosci Biotechnol Biochem. 2009 Dec;73(12):2589-94. Epub 2009 Dec 7.

Ganoderma lucidum extracts inhibited leukemia WEHI-3 cells in BALB/c mice and promoted an immune response in vivo.

Chang YH1, Yang JS, Yang JL, Wu CL, Chang SJ, Lu KW, Lin JJ, Hsia TC, Lin YT, Ho CC, Wood WG, Chung JG.

Author information

Abstract

Ganoderma lucidum (G. lucidum) is a medicinal mushroom having biological effects such as immunomodulation and anti-tumor actions. In China and many other Asian countries, G. lucidum is used as a folk remedy to promote health and longevity. Although many studies have shown that G. lucidum modulates the immune system, including, for example, antigen-presenting cells, natural killer (NK) cells, and the T and B lymphocytes, the effects of G. lucidum on the WEHI-3 leukemic BALB/c mice are unclear. We attempted to determine whether G. lucidum would promote immune responses in BALB/c mice injected with WEHI-3 leukemia cells. The effects of G. lucidum on the survival rate of WEHI-3 leukemia cells injected into BALB/c mice were examined. It increased the percentages of CD3 and CD19, but decreased the percentages of Mac-3 and CD11b markers, suggesting that differentiation of the precursor of T and B cells was promoted but macrophages were inhibited. It decreased the weight of spleens as compared with control mice. It also promoted phagocytosis by macrophage from peripheral blood mononuclear cell (PBMC) and it also promoted natural killer cell activity. It decreased the percentage of leukemia cells in the spleens of mice before they were injected with WEHI-3 cells. Apparently, G. lucidum affects murine leukemia WEHI-3 cells in vivo.

PMID : 19966494 [PubMed – indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov/pubmed/19966494

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