Medicinal mushrooms: Reishi / Linghzi vs. Hepatitis B, cancer, tumors, inflammation

Reishi vs. Hepatitis B

The polysaccharide fractions and triterpenes isolated from Ganoderma lucidum have shown protection effects on the liver in animal studies. This double-blind, randomised, and multicentered study aimed to evaluate the safety and effect of a G. lucidum extraction, Ganopoly, in chronic hepatitis B. Ninety patients with chronic hepatitis B, hepatitis В viral (HBV) DNA positivity, and aminotransferase elevation were included in this multicenter prospective randomized Phase I/II study. Patients were randomized to be given Ganopoly (n = 60) or placebo (n = 30) for 12 weeks, then followed up for 13 weeks. Effect of therapy on levels of HBV DNA and aminotransferase activities in serum and hepatitis В е antigen (HBeAg) status were investigated. There were 78 assessable patients who entered the trial for efficacy and safety; 13 of 52 (25%) patients receiving Ganopoly responded by reducing HBeAg and HBV DNA, compared to 1 of 26 (4%) in the control group (P < 0.05). Among those with serum aspartate aminotransferase (AST) values < 100 U/L (n = 29), 41% (12/29) responded, and among those with AST values > 100 U/L (n = 23), 65% (15/23) responded. Within the 6-month study period, 33% (17/ 52) of treated patients had normal aminotransferase (ALT) values, and 13% (7/52) had cleared hepatitis B surface antigen (HBsAg) from serum, whereas none of the controls had normal ALT values or had lost HBsAg. Eight of 60 patients in Ganopoly group and 4 of 30 in the controls were unable to be followed up due to loss or withdrawal. Our study indicates that Ganopoly is well tolerated and appears to be active against HBV in patients with chronic hepatitis B.

http://www.dl.begellhouse.com/journals/708ae68d64b17c52,72e968661ff5d957,09001a9418679e96.html

Reishi vs. Hepatitis B (II)

Herbal medicines are always considered to be a safe and useful approach for the treatment of chronic hepatopathy. Ganoderma luciudm (Curt.:Fr.) P. Karst. [(Ling Zhi, Reishi mushroom) (Aphyllophoromycetideae)], a highly ranked medicinal mushroom in Oriental traditional medicine, has been widely used for the treatment of chronic hepatopathy of various etiologies. Data from in vitro and animal studies indicate that G. lucidum extracts (mainly polysaccharides or triterpenoids) exhibit protective activities against liver injury induced by toxic chemicals (e.g., CCl4) and Bacillus Calmette-Guerin (BCG) plus lipopolysaccharide (LPS). G. lucidum also showed anti–hepatitis B virus (HBV) activity in a duckling study. Recently, a randomized placebo-controlled clinical study showed that treatment with G. lucidum polysaccharides for 12 weeks reduced hepatitis B e antigen (HBeAg) and HBV DNA in 25% (13/52) patients with HBV infection. The mechanisms of the hepatoprotective effects of G. lucidum have been largely undefined. However, accumulating evidence suggests several possible mechanisms. These include antioxidant and radical-scavenging activity, modulation of hepatic Phase I and II enzymes, inhibition of b-glucuronidase, antifibrotic and antiviral activity, modulation of nitric oxide production, maintenance of hepatocellular calcium homeostasis, and immunomodulating effects. G. lucidum could represent a promising approach for the management of various chronic hepatopathies. Further studies are needed to explore the kinetics and mechanisms of action of G. lucidum constituents with hepatoprotective activities.

http://www.dl.begellhouse.com/journals/708ae68d64b17c52,3389befb6be7818a,3ea891d772a09d0f.html

Reishi vs. tumors

Ganoderma lucidum has been established to be an antitumor natural product. Hot-water extracts of the mycelium of G. lucidum (GLP) exhibited antitumor effect against fibrosarcoma in male and female C3H mice and inhibited the metastasis of the tumor to the lung. Moreover, we have fractionated GLP into polysaccharide fraction [GLP(AI)] and nonpolysaccharide fraction. We found that GLP(AI) is the major component to show the in vivo antitumor effect on fibrosarcoma growth in C3H mice. The effect of PS-G purified from GLP(AI) by Sephadex and ion-exchange column chromatography on the induction of differentiation in leukemic U937 cells was examined. We found that it could stimulate blood mononuclear cells to secrete cytokines, TNF-a, IFN-g, IL-1b, and IL-6, etc., which were both antiproliferative and differentiation-inductive to the leukemic U937 and HL-60 cells. TNF-a and IFN-g, especially, induced apoptosis and differentiation in the treated leukemic cells. Furthermore, antitumor activity of G. lucidum on intraperitioneally implanted Lewis lung carcinoma in syngeneic C57BL/6 mice was investigated. The results showed that GLP significantly increased the lifespan of tumor-implanted mice, when administered intraperioneally alone or in combination with cytotoxic antitumor drugs (adriamycin, fluorouracil, thioguanine, methotrexate, or cisplatin) or a synthetic immunomodulator (imexon). The GLP was not cytotoxic to cultured cells, and the antitumor activity was abolished by pretreatment of mice with cyclosporine. These observations suggest that GLP exerts its antitumor effect mainly through immunopotentiation of the tumor-bearing animals.

http://www.dl.begellhouse.com/journals/708ae68d64b17c52,58cadf0c6c913237,1af485045b17e424.html

Reishi vs. tumors and inflammation

A series of lanostane-type triterpene acids, including eleven lucidenic acids (3, 4, 9, 10, 13–19) and six ganoderic acids (20–22, 24, 26, 27), as well as six sterols (28–33), all isolated from the fruiting bodies of the fungus Ganoderma lucidum, were examined for their inhibitory effects on the induction of Epstein–Barr virus early antigen (EBV-EA) by 12-O-tetradecanoylphorbol-13-acetate (TPA) in Raji cells, a known primary screening test for anti-tumor promoters. All of the compounds tested, except for ganolactone (27) and three sterols (29–31), showed potent inhibitory effects on EBV-EA induction, with IC50 values of 235–370 mol ratio/32 pmol TPA. In addition, nine lucidenic acids (1, 2, 5–8, 11, 12, 18) and four ganoderic acids (20, 23–25) were found to inhibit TPA-induced inflammation (1 μg/ear) in mice, with ID50 values of 0.07–0.39 mg per ear. Further, 20-hydroxylucidenic acid N (18) exhibited inhibitory effects on skin-tumor promotion in an in vivo two-stage mouse-skin carcinogenesis test based on 7,12-dimethylbenz[a]anthracene (DMBA) as initiator, and with TPA as promoter.

http://onlinelibrary.wiley.com/doi/10.1002/cbdv.200790027/full

Reishi vs. cancer

The meta-analysis results showed that patients who had been given G. lucidum alongside with chemo/radiotherapy were more likely to respond positively compared to chemo/radiotherapy alone (RR 1.50; 95% CI 0.90 to 2.51, P = 0.02). G. lucidum treatment alone did not demonstrate the same regression rate as that seen in combined therapy. The results for host immune function indicators suggested that G. lucidum simultaneously increases the percentage of CD3, CD4 and CD8 by 3.91% (95% CI 1.92% to 5.90%, P < 0.01), 3.05% (95% CI 1.00% to 5.11%, P < 0.01) and 2.02% (95% CI 0.21% to 3.84%, P = 0.03), respectively. In addition, leukocyte, NK-cell activity and CD4/CD8 ratio were marginally elevated. Four studies showed that patients in the G. lucidum group had relatively improved quality of life in comparison to controls. One study recorded minimal side effects, including nausea and insomnia. No significant haematological or hepatological toxicity was reported.

Our review did not find sufficient evidence to justify the use of G. lucidum as a first-line treatment for cancer. It remains uncertain whether G. lucidum helps prolong long-term cancer survival. However, G. lucidum could be administered as an alternative adjunct to conventional treatment in consideration of its potential of enhancing tumour response and stimulating host immunity. G. lucidum was generally well tolerated by most participants with only a scattered number of minor adverse events. No major toxicity was observed across the studies. Although there were few reports of harmful effect of G. lucidum, the use of its extract should be judicious, especially after thorough consideration of cost-benefit and patient preference. Future studies should put emphasis on the improvement in methodological quality and further clinical research on the effect of G. lucidum on cancer long-term survival are needed. An update to this review will be performed every two years.

http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD007731.pub3/full

Reishi (Ganoderma Lucidum) vs. cancer

The mushroom Ganoderma lucidum (G. lucidum) has been used for centuries in Asian countries to treat various diseases and to promote health and longevity. Clinical studies have shown beneficial effects of G. lucidum as an alternative adjuvant therapy in cancer patients without obvious toxicity. G. lucidum polysaccharides (GLP) is the main bioactive component in the water soluble extracts of this mushroom. Evidence from in vitro and in vivo studies has demonstrated that GLP possesses potential anticancer activity through immunomodulatory, anti-proliferative, pro-apoptotic, anti-metastatic and anti-angiogenic effects. Here, we briefly summarize these anticancer effects of GLP and the underlying mechanisms.

STUDY 1:

Consumption of reishi mushroom has been reported to prevent colon carcinogenesis in rodents, although the underlying mechanisms remain unclear. To investigate this effect, rats were fed a high-fat diet supplemented with 5% water extract from either the reishi mushroom (Ganoderma lingzhi) (WGL) or the auto-digested reishi G. lingzhi (AWGL) for three weeks. Both extracts markedly reduced fecal secondary bile acids, such as lithocholic acid and deoxycholic acid (colon carcinogens). These extracts reduced the numbers of Clostridium coccoides and Clostridium leptum (secondary bile acids-producing bacteria) in a per g of cecal digesta. Fecal mucins and cecal propionate were significantly elevated by both extracts, and fecal IgA was significantly elevated by WGL, but not by AWGL. These results suggest that the reishi extracts have an impact on colon luminal health by modulating secondary bile acids, microflora, mucins, and propionate that related to colon cancer.

https://www.ncbi.nlm.nih.gov/pubmed/28661219

STUDY 2:

The medical mushroom Ganoderma lucidum (Reishi), a traditional Chinese medicine, has exhibited a promising anti-cancer effect. However, the molecular mechanism of its action on cancer cells remains unclear. Aberrant activation of Wnt/β-catenin signaling pathway is the cause of many types of cancer, including breast cancer. Here we investigated the effect of Reishi on Wnt/β-catenin signaling pathway and elucidated the molecular mechanism of its function in inhibiting breast cancer cells. We found that Reishi blocked Wnt/β-catenin signaling through inhibiting the phosphorylation of Wnt co-receptor LRP6. In human (MDA-MB-231) and mouse (4T1) breast cancer cell lines, Reishi significantly decreased the phosphorylation of LRP6 and suppressed Wnt3a-activated Wnt target gene Axin2 expression. Administration of Reishi inhibited Wnt-induced hyper-proliferation of breast cancer cells and MDA-MB-231 cell migration. Our results provide evidence that Reishi suppresses breast cancer cell growth and migration through inhibiting Wnt/β-catenin signaling, indicating that Reishi may be a potential natural inhibitor for breast cancer.

https://www.ncbi.nlm.nih.gov/pubmed/28427938

STUDY 3:

The present study investigated the anticancer effects and potential mechanisms of BSGLWE on colorectal cancer in vivo and in vitro. Our results showed that BSGLWE significantly inhibited colorectal cancer HCT116 cell viability in a time- and dose-dependent manner. Flow cytometry analysis indicated that BSGLWE disrupted cell cycle progression at G2/M phase via downregulation of cyclin B1 and cyclin A2, and upregulation of P21 at mRNA levels. Moreover, BSGLWE induced apoptosis by decreasing Bcl-2 and survivin at mRNA levels, and reduced Bcl-2, PARP, pro-caspase-3 and pro-caspase-9 at protein levels. Furthermore, BSGLWE suppressed tumor growth in vivo by regulating the expression of genes and proteins associated with cell cycle and apoptosis, which was further confirmed by a reduction of Ki67, PCNA, and Bcl-2 expression as determined by immunohistochemistry staining. NSAID activated gene-1 (NAG-1), a pro-apoptotic gene, was significantly upregulated in vivo and in vitro upon BSGLWE treatment at both mRNA and protein levels. In addition, the relative amounts of secreted NAG-1 in cell culture medium or serum of nude mice were all upregulated upon BSGLWE treatments, suggesting a role of NAG-1 in BSGLWE-induced anticolorectal cancer activity. This is the first study to show that BSGLWE inhibits colorectal cancer carcinogenesis through regulating genes responsible for cell proliferation, cell cycle and apoptosis cascades. These findings indicate that BSGLWE possesses chemopreventive potential in colorectal cancer which may serve as a promising anticancer agent for clinical applications.

https://www.ncbi.nlm.nih.gov/pubmed/28358412

STUDY 4:

The aim of this study is to investigate the anti-inflammatory, anticancer and anti-metastatic activities of Ganoderma lucidum extracts in melanoma and triple-negative breast cancer cells. Ganoderma lucidum extracts were prepared by using common organic solvents; MDA-MB 231 and B16-F10 cell lines were adopted as cellular models for triple-negative breast cancer and melanoma and characterized for cell viability, wound-healing assay and measurement of cytokines secreted by cancer cells under pro-inflammatory conditions (incubation with lipopolysaccharide, LPS) and pretreatment with Ganoderma lucidum extract at different concentrations. Our study demonstrates, for the first time, how Ganoderma lucidum extracts can significantly inhibit the release of IL-8, IL-6, MMP-2 and MMP-9 in cancer cells under pro-inflammatory condition. Interestingly, Ganoderma lucidum extracts significantly also decrease the viability of both cancer cells in a time- and concentration-dependent manner, with abilities to reduce cell migration over time, which is correlated with a lower release of matrix metalloproteases. Taken together, these results indicate the possible use of Ganoderma lucidum extract for the therapeutic management of melanoma and human triple-negative breast cancer.

https://www.ncbi.nlm.nih.gov/pubmed/28264501

STUDY 5:

G. lucidum polysaccharides – mainly β-glucans and heteroglycans – have numerous biological properties such as antitumour and immunomodulatory activities. This report shows, by gene expression analyses and bioenergetic assays, immunomodulatory properties and capacity to improve glucose metabolism of a water-soluble heteroglycan extracted from mycelium of an Italian isolate of G. lucidum. The findings suggest the use of the heteroglycan as probiotic or ingredient in functional foods, being easy to produce and disperse in a food matrix thanks to its water-solubility. Heteroglycan could exert protective effects in pro-inflammatory conditions and benefits for people characterised by suppressed immune response.

https://www.ncbi.nlm.nih.gov/pubmed/28105862