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Oral Administration of Agaricus blazei (H1 Strain) Inhibited Tumor Growth in a Sarcoma 180 Inoculation Model
Yun-Lyul LEE, Heui-Jin KIM, Mi-Sook LEE, Ji-Min KIM, Jin-Soo HAN, Euk-Ki HONG, Myung-Sang KWON, Min-Jae
Abstract

Agaricus blazei (H1 strain) was tested for its anticancer activity using a sarcoma 180 (S180) inoculation model and the changing patterns of splenocyte subsets were examined. Its hot-water extract was administered orally to ICR and KSN nude mice that were inoculated with S180. The growth of S180 was significantly inhibited in A.blazei treated groups. Pan T cells significantly increased in all treated groups compared to controls, even in KSN nude mice. Splenocyte subset changes were slightly different between ICR and KSN nude mice. This S180 inoculation model proved to be effective in screening the antitumor effect of basidiomycetes and allowed comparisons of immunological cellular changes between the mouse strains.






Inhibitory effects of Agaricus blazei extracts on human myeloid leukemia cells

Chi-FaiKimaJing-JingJiangaKwok-NamLeungbKwok-PuiFungbcClara Bik-SanLauac

Abstract
Ethnopharmacological relevance
Agaricus blazei has been used as an adjuvant in cancer chemotherapy and is found to inhibit the growth of various types of tumor cells.
Aim of the study
Our study has adopted a systematic and bioassay-guided approach to optimize the extraction of Agaricus blazei for anti-leukemic bioactive components. The tumor-selective growth inhibitory activity of the extracts on leukemic cell lines was evaluated in vitro and in vivo using tumor-bearing nude mice.
Results
The JAB80E70 extract showed the most potent tumor-selective growth inhibitory activity against human leukemia NB-4 and K-562 cells. This is the first report of anti-leukemic activity of JAB80E70 in athymic nude mice bearing NB-4 cells. Using DNA fragmentation assays and cell death detection ELISA, JAB80E70 was found to induce apoptosis in NB-4 cells. However, the polysaccharide enriched fractions failed to show significant cytotoxicity on NB-4 cells in vitro.
Conclusions
The JAB80E70 extract exhibited potent anti-leukemic effect in vitro and in vivo. The effect can be attributed, at least in part, to the induction of apoptosis. Besides, polysaccharides in Agaricus blazei may not possess direct anti-leukemic activity in vitro.


Inhibitory mechanisms of Agaricus blazei Murill on the growth of prostate cancer in vitro and in vivo

Ching-HanYuaShu-FenKanaChin-HangShubTing-JangLucLucySun-HwangcPaulus S.Wangad
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https://doi.org/10.1016/j.jnutbio.2008.07.004Get rights and content

Abstract
Agaricus blazei Murill (A. blazei) has been conventionally used as a health food for the prevention of cancer. However, little is known about the direct effects and action mechanisms of A. blazei on human prostate cancer. In the present study, the effects of A. blazei on the growth of human prostate cancer were examined in vitro and in vivo. A. blazei, especially the broth fraction, inhibited cell proliferation in both androgen-dependent and androgen-independent prostate cancer cell lines. The broth of A. blazei induced lactate dehydrogenase leakage in three cancer cell lines, whereas the activities of caspase 3 and the DNA fragmentation were enhanced the most in androgen-independent PC3 cells. The protein expressions of apoptosis-related molecules were elevated by the broth of A. blazei in PC3 cells. Oral supplementation with the broth of A. blazei (with the higher ratio of β-glucan) significantly suppressed tumor growth without inducing adverse effects in severe combined immunodeficient mice with PC3 tumor xenograft. Tumor xenografts from A. blazei-fed mice showed decreased proliferating cell nuclear antigen-positive cells and reduced tumor microvessel density. Based on these results, we found that the broth of A. blazei may directly inhibit the growth of prostate cancer cell via an apoptotic pathway and suppress prostate tumor growth via antiproliferative and antiangiogenic mechanisms. We therefore suggest that A. blazei might have potential therapeutic use in the prevention and treatment of human prostate cancer.







Antitumor Activity and Some Properties of Water-soluble Polysaccharides from "Himematsutake, " the Fruiting Body of Agaricm blazei Murill
Takashi MIZUNO, Toshihiko HAGIWARA, Takuji NAKAMURA, Hitoshi Tro, Keishiro SHIMURA, Toshimitsu SUMIYA, Akihiro ASAKURA


Abstract
Polysaccharides extracted from Himematsutake, the fruiting body of Agaricus blazei Murill with hot water were fractionated and purified by ethanol precipitation, ion-exchange chromatography, gel-filtration, affinity chromatography, etc.
A total of 17 polysaccharide samples thus obtained were given an antitumor activity test (Sarcoma 180/mice i.p. p.o. method) and traces of their activities through the fractionation and purification processes were found.
FI0-a-β, FA-1-a-α, FA-1-a-β, and FA-2-b-β, were obtained as water soluble polysaccharides fractions having great antitumor activities.
Analyses of physico-chemical properties and IR- and NMR-spectra of these active fractions showed that their main components were: FI0-a-β, (1→6)-; (1→3)-β-D-glucan; FA-1-a-α, acidic (1→6)-; (1→4)-α-D-glucan; FA-1-a-β, acidic (1→6)-; (1→3)-α-D-glucan; and FA-2-b-β, acidic RNA-protein complex.









Antitumor Activity and Some Properties of Water-insoluble Hetero-glycans from “Himematsutake,” the Fruiting Body of Agaricus blazei Murill
Takashi Mizuno,Ryuichi Inagaki,Tetsuro Kanao,Toshihiko Hagiwara,Takuji Nakamura,

Abstract
After extraction of a hot-water-soluble polysaccharide (FI) from the fruiting bodies of Himematsutake (Agaricus blazei Murill), water-insoluble polysaccharides were obtained by successive extraction with 1% ammonium oxalate solution (FII), 5% sodium hydroxide solution (FIII and FIV), 20% sodium hydroxide solution (FV), and 5% lithium chloride-dimethylacetamide solution (FVI) in that order. These water-insoluble fractions were further fractionated by ethanol precipitation, gel-filtration, etc. Polysaccharides, polysaccharide-protein complexes, and chitin substances thus obtained were assayed for their antitumor activities using the Sarcoma 180/mice i.p., p.o. method.
The heteroglycan-protein complexes, FH-a, -b and -c, obtained from FII had weak antitomor activities.
A remarkable antitumor activity was found in a glycoprotein, FIII-2-b, fractionated and purified from Fill. The polysaccharide portion of this polysaccharide-protein complex (polysaccharide, 50.2% and protein, 43.3% each on a weight basis) consisted of (l → 6)-β-d-glucan, and its protein portion was rich in Asx, Glx, Ala, Leu, and Pro.
A high antitumor activity was found in a xyloglucan-protein complex, FIV-2-b, fractionated and purified from FIV.
Antitumor activity was found also in a glucoxylan, FV-2-a, obtained from FV.
No significant antitumor activity was found in a chitin substance, FVI.










Improving effects of the mushroom Yamabushitake (Hericium erinaceus) on mild cognitive impairment: a double-blind placebo-controlled clinical trial.
Mori K1, Inatomi S, Ouchi K, Azumi Y, Tuchida T.
Author information
Abstract
A double-blind, parallel-group, placebo-controlled trial was performed on 50- to 80-year-old Japanese men and women diagnosed with mild cognitive impairment in order to examine the efficacy of oral administration of Yamabushitake (Hericium erinaceus), an edible mushroom, for improving cognitive impairment, using a cognitive function scale based on the Revised Hasegawa Dementia Scale (HDS-R). After 2 weeks of preliminary examination, 30 subjects were randomized into two 15-person groups, one of which was given Yamabushitake and the other given a placebo. The subjects of the Yamabushitake group took four 250 mg tablets containing 96% of Yamabushitake dry powder three times a day for 16 weeks. After termination of the intake, the subjects were observed for the next 4 weeks. At weeks 8, 12 and 16 of the trial, the Yamabushitake group showed significantly increased scores on the cognitive function scale compared with the placebo group. The Yamabushitake group's scores increased with the duration of intake, but at week 4 after the termination of the 16 weeks intake, the scores decreased significantly. Laboratory tests showed no adverse effect of Yamabushitake. The results obtained in this study suggest that Yamabushitake is effective in improving mild cognitive impairment.
(c) 2008 John Wiley & Sons, Ltd.
(ci)









Cordycepin protects renal ischemia/reperfusion injury through regulating inflammation, apoptosis, and oxidative stress.
Han F1, Dou M1, Wang Y1, Xu C1,2, Li Y1,3, Ding X1,3, Xue W1,3, Zheng J1,3, Tian P1,3, Ding C1,3.
Author information
Abstract
Cordycepin (3'-deoxyadenosine) is a naturally occurring adenosine analog and one of the bioactive constituents isolated from Cordyceps sinensis, species of the fungal genus Cordyceps. It has traditionally been a prized Chinese folk medicine for the human well-being. However, the actions of cordycepin against renal ischemia/reperfusion injury (I/R) are still unknown. In the present study, rats were subject to I/R and cordycepin was intragastrically administered for seven consecutive days before surgery to investigate the effects and mechanisms of cordycepin against renal I/R injury. The test results of kidney and peripheral blood samples of experimental animals showed that cordycepin significantly decreased serum blood urea nitrogen and creatinine levels and markedly attenuated cell injury. Mechanistic studies showed that cordycepin significantly regulated inflammation, apoptosis, and oxidative stress. These data provide new insights for investigating the natural product with the nephroprotective effect against I/R, which should be developed as a new therapeutic agent for the treatment of I/R in the future.
© The Author(s) 2020. Published by Oxford University Press on behalf of the Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.









Cordyceps sinensis prevents contrast-induced nephropathy in diabetic rats: its underlying mechanism.
Zhao K1, Gao Q2, Zong C2, Ge L3, Liu J2.
Author information
Abstract
Apoptosis is recognized as an important mechanism in contrast-induced nephropathy (CIN). This study investigated the renal protective effect of cordyceps sinensis (CS) in a diabetic rat model of CIN and the mechanism of its effect. Sixty SD rats were randomly divided into 4 groups, the control group, model group, probucol group, and CS group. We used a diabetic rat model of Iodixanol-induced CIN. Serum creatinine (Scr), blood urea nitrogen (BUN), urinary kidney injury molecule-1 (KIM-1), neutrophil gelatinase associated lipocalin (NGAL) levels were measured to evaluate renal function. Total antioxidative ability (T-AOC), superoxide dismutase (SOD), and malonaldehyde (MDA) levels were assessed to discuss the effect of probucol and CS on oxidative stress. The pathologic changes in the kidney were observed by hematoxylin and eosin (HE) staining and periodic acid-Schiff (PAS) staining. Apoptosis was assessed by transmission electron microscopy and TUNEL staining. Caspase-3, Bax, Bcl2 and phospho-p38 mitogen-activated protein kinase (MAPK) protein expressions were assessed by Western blotting. The model group of rats showed significantly elevated levels of BUN, Scr, urinary KIM-1, NGAL, and parameters of oxidative stress (P<0.05). Both the probucol and CS groups demonstrated significantly lower Scr, BUN, and urinary KIM-1, NGAL levels compared to the model group (P<0.05), with no significant difference between these two groups. The probucol group and the CS group had significantly lower MDA and higher T-AOC, SOD than the model group after modeling (P<0.05). Caspase-3, Bax activation were effectively repressed while Bcl-2 expression was increased by probucol and CS pretreatment. Mechanistically, probucol and CS decreased the expression of JNK protein and increased the expression of ERK protein. CS can effectively reduce kidney damage caused by contrast medium. The underlying mechanism may be that CS accelerates the recovery of renal function and renal pathology by reducing local renal oxidative stress and influencing MAPK signal pathways.
IJCEP Copyright © 2018.








Anticancer and antimetastatic effects of cordycepin, an active component of Cordyceps sinensis

Kazuki, Nakamura, Kazumasa, Shinozuka, Noriko Yoshikawaa
a
Department of Pharmacology, School of Pharmacy and Pharmaceutical Sciences, 11-68, Koshien Kyuban-cho, Nishinomiya, Hyogo 663-8179, Japan
b
Institute for Biosciences, Mukogawa Women's University, 11-68, Koshien Kyuban-cho, Nishinomiya, Hyogo 663-8179, Japan
Received 21 August 2014, Revised 9 September 2014, Accepted 10 September 2014, Available online 22 October 2014.
Abstract
Cordyceps sinensis, a fungus that parasitizes on the larva of Lepidoptera, has been used as a valued traditional Chinese medicine. We investigated the effects of water extracts of Cordyceps sinensis (WECS), and particularly focused on its anticancer and antimetastatic actions. Based on in vitro studies, we report that WECS showed an anticancer action, and this action was antagonized by an adenosine A3 receptor antagonist. Moreover, this anticancer action of WECS was promoted by an adenosine deaminase inhibitor. These results suggest that one of the components of WECS with an anticancer action might be an adenosine or its derivatives. Therefore, we focused on cordycepin (3′-deoxyadenosine) as one of the active ingredients of WECS. According to our experiments, cordycepin showed an anticancer effect through the stimulation of adenosine A3 receptor, followed by glycogen synthase kinase (GSK)-3β activation and cyclin D1 suppression. Cordycepin also showed an antimetastatic action through inhibiting platelet aggregation induced by cancer cells and suppressing the invasiveness of cancer cells via inhibiting the activity of matrix metalloproteinase (MMP)-2 and MMP-9, and accelerating the secretion of tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2 from cancer cells. In conclusion, cordycepin, an active component of WECS, might be a candidate anticancer and antimetastatic agent.






Reinforcement of antitumor effect of Cordyceps sinensis by 2'-deoxycoformycin, an adenosine deaminase inhibitor.
Yoshikawa N1, Nakamura K, Yamaguchi Y, Kagota S, Shinozuka K, Kunitomo M.
Author information
Abstract
In this study, an attempt was made to elucidate the combined effect of 2'-deoxycoformycin (DCF), an adenosine deaminase inhibitor, with a water extract of Cordyceps sinensis (WECS), on the growth curves of mouse melanoma and lung carcinoma cells. Sub-confluent cells were harvested with an EDTA trypsin solution, and resuspended to appropriate concentrations in DMEM containing 10% fetal bovine serum. Using 1x10(5) cells/2 ml in each well of a 12-well culture plate, cells were incubated for 24, 48 and 72 h in the presence of WECS alone, or WECS plus DCF in a CO2 incubator at 37 degrees C. Duplicate samples of viable cells were enumerated with a Coulter counter. The antitumor effect of WECS on the growth curves of tumor cell lines increased over 3-fold in combination with DCF. These results suggest that DCF has a remarkable reinforcement effect on the antitumor activity of WECS. DCF is a potent adjuvant for WECS.









Cordycepin inhibits human ovarian cancer by inducing autophagy and apoptosis through Dickkopf-related protein 1/β-catenin signaling.
Jang HJ1,2, Yang KE1, Hwang IH3, Huh YH4, Kim DJ5, Yoo HS6, Park SJ7, Jang IS1,8.
Author information
Abstract
Cordycepin, the major active component from Cordyceps militaris, has been reported to significantly inhibit some types of cancer; however, its effects on ovarian cancer are still not well understood. In this study, we treated human ovarian cancer cells with different doses of cordycepin and found that it dose-dependently reduced ovarian cancer cell viability, based on Cell counting kit-8 reagent. Immunoblotting showed that cordycepin increased Dickkopf-related protein 1 (Dkk1) levels and inhibited β-catenin signaling. Atg7 knockdown in ovarian cancer cells significantly inhibited cordycepin-induced apoptosis, whereas β-catenin overexpression abolished the effects of cordycepin on cell death and proliferation. Furthermore, we found that Dkk1 overexpression by transfection downregulated the expression of c-Myc and cyclin D1. siRNA-mediated Dkk1 silencing downregulated the expression of Atg8, beclin, and LC3 and promoted β-catenin translocation from the cytoplasm into the nucleus. These results suggest that cordycepin inhibits ovarian cancer cell growth, possibly through coordinated autophagy and Dkk1/β-catenin signaling. Taken together, our findings provide new insights into the treatment of ovarian cancer using cordycepin.
AJTR Copyright © 2019.








Antigenotoxic and antioxidant potential of medicinal mushrooms (Immune Assist) against DNA damage induced by free radicals-an in vitro study.
Živković L1, Bajić V2, Bruić M3, Borozan S4, Popić K3, Topalović D3, Santibanez J5, Spremo-Potparević B3.
Author information
Abstract
Immune Assist (IA) is produced from extract of six species of medical mushrooms: Agaricus blazei - Cordyceps sinensis - Grifola frondosa - Ganoderma lucidum - Coriolus versicolor - Lentinula edodes. The genoprotective potential of IA was evaluated for the first time. Significant antigenotoxic effects were detected in human peripheral blood cells against H2O2 induced DNA damage, in the pretreatment and in the posttreatment. The most efficient concentration of IA in pretreatment was 500 μg/mL, while in posttreatment it was the concentration of 250 μg/mL. Kinetics of attenuation of H2O2 induced DNA damage in posttreatment with the optimal concentration of IA showed significant decrease in the number of damaged cells at all time periods (15-60 min), reaching the greatest reduction after 15 and 45 min. Remarkable ·OH scavenging properties and moderate reducing power, together with the modest DPPH scavenging activity, could be responsible for the great attenuation of DNA damage after 15 min of exposure to IA, while reduction of DNA damage after 45 min could be the result in additional stimulation of the cell's repair machinery. Our results suggest that IA displayed antigenotoxic and antioxidant properties. A broader investigation of its profile in biological systems is needed.








Cordycepin induces apoptosis in human bladder cancer T24 cells through ROS-dependent inhibition of the PI3K/Akt signaling pathway.
Kim SO1,2, Cha HJ3, Park C4, Lee H5,6, Hong SH5,6, Jeong SJ7, Park SH8, Kim GY9, Leem SH10, Jin CY11, Hwang EJ2, Choi YH5,6.
Author information
Abstract
Cordycepin, a derivative of nucleoside adenosine, is one of the active ingredients extracted from the fungi of genus Cordyceps, which have been used for traditional herbal remedies. In this study, we examined the effect of cordycepin on the proliferation and apoptosis of human bladder cancer T24 cells and its mechanism of action. Cordycepin treatment significantly reduced the cell survival rate of T24 cells in a concentration-dependent manner, which was associated with the induction of apoptosis. Cordycepin activated caspase-8 and -9, which are involved in the initiation of extrinsic and intrinsic apoptosis pathways, respectively, and also increased caspase-3 activity, a typical effect caspase, subsequently leading to poly (ADP-ribose) polymerase cleavage. Additionally, cordycepin increased the Bax/Bcl-2 ratio and truncation of Bid, and destroyed the integrity of mitochondria, which contributed to the cytosolic release of cytochrome c. Moreover, cordycepin effectively inactivated the phosphoinositide 3-kinase (PI3K)/Akt signaling pathway, while LY294002, a PI3K/Akt inhibitor, increased the apoptosis-inducing effect of cordycepin. Cordycepin further enhanced the intracellular levels of reactive oxygen species (ROS), while the addition of N-acetyl cysteine (NAC), a ROS inhibitor, significantly diminished cordycepin-induced mitochondrial dysfunction and growth inhibition, and also blocked the inactivation of PI3K/Akt signaling pathway. Furthermore, the presence of NAC significantly attenuated the enhanced apoptotic cell death and reduction of cell viability by treatment with cordycepin and LY294002. Collectively, the data indicate that cordycepin induces apoptosis through the activation of extrinsic and intrinsic apoptosis pathways and the ROS-dependent inactivation of PI3K/Akt signaling in human bladder cancer T24 cells.







The Inhibitory Effect of Cordycepin on the Proliferation of MCF-7 Breast Cancer Cells, and its Mechanism: An Investigation Using Network Pharmacology-Based Analysis.
Lee D1, Lee WY2, Jung K3, Kwon YS4, Kim D5, Hwang GS2, Kim CE2, Lee S6, Kang KS7.
Author information
Abstract
Cordyceps militaris is a well-known medicinal mushroom. It is non-toxic and has clinical health benefits including cancer inhibition. However, the anticancer effects of C. militaris cultured in brown rice on breast cancer have not yet been reported. In this study, we simultaneously investigated the anticancer effects of cordycepin and an extract of C. militaris cultured in brown rice on MCF-7 human breast cancer cells using a cell viability assay, cell staining with Hoechst 33342, and an image-based cytometric assay. The C. militaris concentrate exhibited significant MCF-7 cell inhibitory effects, and its IC50 value was 73.48 µg/mL. Cordycepin also exhibited significant MCF-7 cell inhibitory effects, and its IC50 value was 9.58 µM. We applied network pharmacological analysis to predict potential targets and pathways of cordycepin. The gene set enrichment analysis showed that the targets of cordycepin are mainly associated with the hedgehog signaling, apoptosis, p53 signaling, and estrogen signaling pathways. We further verified the predicted targets related to the apoptosis pathway using western blot analysis. The C. militaris concentrate and cordycepin exhibited the ability to induce apoptotic cell death by increasing the cleavage of caspase-7 -8, and -9, increasing the Bcl-2-associated X protein/ B-cell lymphoma 2 (Bax/Bcl-2) protein expression ratio, and decreasing the protein expression of X-linked inhibitor of apoptosis protein (XIAP) in MCF-7 cells. Consequently, the C. militaris concentrate and cordycepin exhibited significant anticancer effects through their ability to induce apoptosis in breast cancer cells.







Protective effect of Cordyceps sinensis extract on lipopolysaccharide-induced acute lung injury in mice.
Fu S1, Lu W2, Yu W3, Hu J2.
Author information
Abstract
Background: To study the protective effect of Cordyceps sinensis extract (Dong Chong Xia Cao in Chinese [DCXC]) on experimental acute lung injury (ALI) mice.Methods and results: ALI model was induced by intratracheal-instilled lipopolysaccharide (LPS, 2.4 mg/kg) in BALB/c male mice. The mice were administrated DCXC (ig, 10, 30, 60 mg/kg) in 4 and 8 h after receiving LPS. Histopathological section, wet/dry lung weight ratio and myeloperoxidase activity were detected. Bronchoalveolar lavage fluid (BALF) was collected for cell count, the levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6) and nitric oxide (NO) in BALF was detected by ELISA, the protein and mRNA expression of nuclear factor-κB p65 (NF-κB p65), inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) in lung tissue was detected by Western blot and RT-PCR. The result showed that DCXC could reduce the degree of histopathological injury, wet/dry weight ratio (W/D ratio) and myeloperoxidase activity (P<0.05) with a dose-dependent manner. The increased number of total cells, neutrophils and macrophages in BALF were significantly inhibited by DCXC treatment (P<0.05). The increased levels of TNF-α, IL-1β, IL-6 and NO in BALF after LPS administration was significantly reduced by DCXC (P<0.05). In addition, the increased protein and mRNA levels of iNOS, COX-2 and NF-κB p65 DNA binding ability in LPS group were dose-dependently reduced by DCXC treatment (P<0.05).Conclusion: DCXC could play an anti-inflammatory and antioxidant effect on LPS-induced ALI through inhibiting NF-κB p65 phosphorylation, and the expression of COX-2 and iNOS in lung. The result showed that DCXC has a potential protective effect on the ALI.
© 2019 The Author(s).







Randomized double-blind placebo-controlled clinical trial and assessment of fermentation product of Cordyceps sinensis (Cs-4) in enhancing aerobic capacity and respiratory function of the healthy elderly volunteers
Xiao Yi, 
Huang Xi-zhen & 
Zhu Jia-shi 
Chinese Journal of Integrative Medicine  10, 187–192(2004)Cite this article

Abstract
Objective: Cordyceps sinensis (CS) is a popular natural Chinese herbal medicine for invigoration, health preservation and reducing fatigue. Its natural substance has been prepared as a fermentation product of a specific strain of Cordyceps sinensis (Cs-4). Our objective was to assess the effect of Cs-4 on the exercise capacity of the healthy elderly people in a randomized, double-blind, placebo-controlled trial.Methods: Thirty-seven healthy, elderly Chinese subjects were randomly assigned to receive either Cs-4 (3 g/ day) or identical placebo capsules. Their exercise performance was tested before and after 6 weeks of treatment with a symptom-limited, incremental work rate protocol on a cycle ergometer. Maximum oxygen uptake (VO2max) was measured using a metabolic chart. Anaerobic thresholds (VO2θ) were identified by two observers using plots of both VCO2 vs VO2 and VE/VO2 vs time.Results: After taking Cs-4 for 6 weeks, VO2max (1.88 ±0.13 to 2.00 ±0.14 L/min;P = 0.050) and VO2θ (1.15 ±0.07 to 1.30 ±0.09 L/min;P = 0.012) were significantly increased, whereas after placebo application they were unchanged.Conclusion: These findings support the belief held in China that Cs-4 could improve oxygen uptake or aerobic capacity and ventilation function and resistance to fatigue of elderly people in exercise.


Effect of Cs-4® (Cordyceps sinensis) on Exercise Performance in Healthy Older Subjects: A Double-Blind, Placebo-Controlled Trial
Steve Chen, M.D., Zhaoping Li, M.D., Ph.D., [...], and Christopher B. Cooper, M.D.
Additional article information
Abstract
Objective
The objective of this study was to examine the effect of Cs-4® (Cordyceps sinensis) on exercise performance in healthy elderly subjects.
Design
Twenty (20) healthy elderly (age 50–75 years) subjects were enrolled in this double-blind, placebo-controlled, prospective trial. The subjects were taking either Cs-4 333 mg or placebo capsules 3 times a day for 12 weeks.
Measurement
Subjects received baseline screening including physical examination and laboratory tests. Maximal incremental exercise testing was performed on a stationary cycle ergometer using breath-by-breath analysis at baseline and at the completion of the study.
Results
After receiving Cs-4 for 12 weeks, the metabolic threshold (above which lactate accumulates) increased by 10.5% from 0.83 ± 0.06 to 0.93 ± 0.08 L/min (p < 0.02) and the ventilatory threshold (above which unbuffered H+ stimulates ventilation) increased by 8.5% from 1.25 ± 0.11 to 1.36 ± 0.15 L/min. Significant changes in metabolic or ventilatory threshold were not seen for the subjects in the placebo group after 12 weeks, and there were no changes in V̇o2 max in either group.
Conclusion
This pilot study suggests that supplementation with Cs-4 (Cordyceps sinensis) improves exercise performance and might contribute to wellness in healthy older subjects.



Cordyceps sinensis: Genotoxic Potential in Human Peripheral Blood Cells and Antigenotoxic Properties Against Hydrogen Peroxide by Comet Assay.
Vasiljevic JD, Zivkovic LP, Cabarkapa AM, Bajic VP, Djelic NJ, Spremo-Potparevic BM.
Abstract
Context • Cordyceps sinensis (C sinensis) is a well-known, traditional, Chinese medicinal mushroom, valued for its beneficial properties for human health. C sinensis has been reported to have immunomodulatory, anticancer, antiaging, antioxidant and anti-inflammatory activity. Despite potential medicinal benefits, no previously published reports are available about the genotoxicity or antigenotoxicity of C sinensis, as detected by comet assay. Objective • The objective of the study was to evaluate both the genotoxic and antigenotoxic potential of an extract of C sinensis (CS extract) in human peripheral blood cells. Design • The research team designed a pilot study. Setting •The study was conducted at the Center for Biological Research, University of Belgrade, in Belgrade, Serbia. Participants • Participants were 6 healthy individuals (2 males and 4 females), between the ages of 20 and 45 y, recruited on a voluntary basis, who provided heparinized, peripheral blood samples. Intervention • Four concentrations of the CS extract-125 μg/mL, 250 μg/mL, 500 μg/mL, and 1000 μg/mL-were used in the treatment of tested blood cells from the blood samples. Three independent procedures were performed: (1) a genotoxicity assessment, (2) an antigenotoxicity assessment for pretreatment of human cells with the CS extract prior to their exposure to hydrogen peroxide (H2O2) (ie, an evaluation of the benefits of the CS extract as a preventive agent); and (3) posttreatment of human cells with the CS extract after their exposure to H2O2 (ie, an evaluation of the benefits of the CS extract as an interventional agent). Outcome Measures • Cells were graded by eye inspection into 5 classes, depending on the extent of DNA damage, representing: (1) class A-undamaged cells with no tail (<5% damaged DNA); (2) class B-low-level damage (5%-20%); (3) class C-medium-level damage (20%-40%); (4) class D-high-level damage (40%-95%), and (5) class E-total destruction (>95%).Results • The CS extract proved to be nongenotoxic because no induced DNA damage was detected at all tested concentrations. For the antigenotoxicity assessment of the pretreatment with the CS extract, only the 1000-µg/mL concentration showed a significant decrease in the number of cells exhibiting H2O2-induced DNA damage. For the posttreatment, the CS extract exhibited antigenotoxic potential by attenuating H2O2-induced DNA damage at all concentrations tested. The evaluation of repair kinetics showed a decrease in DNA-damaged cells 15 min after the application of the CS extract, reaching a maximum potency after 45 min. Conclusions • The results indicated that C sinensis can be used as a postapplicative agent that counteracts the effect of oxidative stress. The resulting reduction in DNA damage might be related to its scavenging properties and stimulation of DNA repair.








Antiaging effect of Cordyceps sinensis extract.
Ji DB1, Ye J, Li CL, Wang YH, Zhao J, Cai SQ.
Author information
Abstract
This experiment studied the effect of Cordyceps sinensis extract (CSE) on mice aged by d-galactose and castrated rats to analyse its antiaging effect. Water maze and step-down type avoidance tests were used to examine the effect of CSE on learning and memory. CSE shortened escape latency, prolonged step-down latency and decreased the number of errors in mice aged by d-galactose. The effect of CSE on the sexual function of castrated rats was evaluated by measuring the penis erection latency, mount latency and ejaculation latency. CSE appeared to shorten penis erection latency and mount latency in castrated rats. The study also measured the effect of CSE on the activity of age-related enzymes. The results showed that CSE improved the activity of superoxide dismutase, glutathione peroxidase and catalase and lowered the level of lipid peroxidation and monoamine oxidase activity in the aged mice. The study demonstrated that CSE can improve the brain function and antioxidative enzyme activity in mice with d-galactose-induced senescence and promote sexual function in castrated rats. All of these findings suggest that CSE has an antiaging effect.
Copyright 2008 John Wiley & Sons, Ltd.








Cordyceps sinensis oral liquid prolongs the lifespan of the fruit fly, Drosophila melanogaster, by inhibiting oxidative stress
YINGXIN ZOU, YUXIANG LIU, [...], and ZESHENG ZHANG
Additional article information
Abstract
This study investigated the effect of Cordyceps sinensis oral liquid (CSOL) on the lifespan of Drosophila melanogaster (fruit fly). Following the lifelong treatment of fruit flies with CSOL, lifespan was examined. The activity of copper-zinc-containing superoxide dismutase 1 (SOD1), manganese-containing superoxide dismutase 2 (SOD2) and catalase (CAT), as well as the lipofuscin (LF) content were determined. The mRNA levels of SOD1, SOD2 and CAT were quantified by qPCR. Hydrogen peroxide (H2O2) and paraquat were used to mimic the effects of damage caused by acute oxidative stress. D-galactose was used to mimic chronic pathological aging. CSOL significantly prolonged the lifespan of the fruit flies under physiological conditions. The activity of SOD1 and CAT was upregulated, and LF accumulation was inhibited by CSOL. CSOL had no effect on the transcriptional levels (mRNA) of these enzymes. The survival time of the fruit flies which were negatively affected by exposure to H2O2 or paraquat was significantly prolonged by CSOL. In fruit flies pathologically aged by epxosure to D-galactose, CSOL also significantly prolonged their lifespan, upregulated the activity of SOD1 and CAT, and inhibited LF accumulation. The findings of our study indicate that CSOL prolongs the lifespan of fruit flies through an anti-oxidative stress pathway involving the upregulation of SOD1 and CAT activity and the inhibition of LF accumulation. CSOL may thus be explored as a novel agent for slowing the human aging process.






Pharmacological actions of Cordyceps, a prized folk medicine.
Ng TB1, Wang HX.
Author information
Abstract
Cordyceps species, including C. sinensis, C. militaris, C. pruinosa and C. ophioglossoides, are prized traditional medicinal materials. The aim of this article is to review the chemical constituents and pharmacological actions of Cordyceps species. The chemical constituents include cordycepin (3'-de-oxyadenosine) and its derivatives, ergosterol, polysaccharides, a glycoprotein and peptides containing alpha-aminoisobutyric acid. They include anti-tumour, anti-metastatic, immunomodulatory, antioxidant, anti-inflammatory, insecticidal, antimicrobial, hypolipidaemic, hypoglycaemic, anti-ageing, neuroprotective and renoprotective effects. Polysaccharide accounts for the anti-inflammatory, antioxidant, anti-tumour, anti-metastatic, immunomodulatory, hypoglycaemic, steroidogenic and hypolipidaemic effects. Cordycepin contributes to the anti-tumour, insecticidal and antibacterial activity. Ergosterol exhibits anti-tumour and immunomodulatory activity. A DNase has been characterized.








Inhibitory effects of ethyl acetate extract of Cordyceps sinensis mycelium on various cancer cells in culture and B16 melanoma in C57BL/6 mice.
Wu JY1, Zhang QX, Leung PH.
Author information
Abstract
The cultivated mycelium of a Cordyceps sinensis (Cs) fungus was sequentially extracted by petroleum ether (PE), ethyl acetate (EtOAc), ethanol (EtOH) and hot water. All solvent extracts except hot water extract showed a significant and dose-dependent inhibitory effect on the proliferation of four cancer cell lines, MCF-7 breast cancer, B16 mouse melanoma, HL-60 human premyelocytic leukemia and HepG2 human hepatocellular carcinoma, with IC(50) values below 132 microg/ml. The EtOAc extract, in particular, had the most potent effect against all four cancer cell lines, with IC(50) between 12 microg/ml (on B16) and 45 microg/ml (on MCF-7). In contrast, it had much lower cytotoxicity against normal mouse bone marrow cells. The EtOAc extract contained carbohydrates, adenosine, ergosterol and trace amount of cordycepin, of which ergosterol and related compounds were identified as a major class of active constituents contributing to the in vitro cytotoxicity. In an animal test, the EtOAc extract showed significant inhibiting effect on B16-induced melanoma in C57BL/6 mice, causing about 60% decrease of tumor size over 27 days. Our results suggest that the EtOAc extract of Cs fungal mycelium has strong anti-tumor activity and is a potential source of natural anti-tumor products.
PMID: 
16423520 
DOI: 
10.1016/j.phymed.2005.11.005







Inhibitory effect of Cordyceps sinensis on spontaneous liver metastasis of Lewis lung carcinoma and B16 melanoma cells in syngeneic mice.
Nakamura K1, Yamaguchi Y, Kagota S, Kwon YM, Shinozuka K, Kunitomo M.
Author information
Abstract
We investigated the effect of the water extract of Cordyceps sinensis (WECS) on liver metastasis of Lewis lung carcinoma (LLC) and B16 melanoma (B16) cells in mice. C57BL/6 mice were given a s.c. injection of LLC and B16 cells and sacrificed 20 and 26 days after tumor inoculation, respectively. WECS was daily administered p.o. to the mice in a dose of 100 mg/kg body weight (wt.) in the experiment of LLC and in a dose of 100 or 200 mg/kg body wt. in the experiment of B16 from one week before tumor inoculation to one day before the date of sacrifice. The tumor cells increased in the thigh in LLC-inoculated mice and in the footpad in B16-inoculated mice. The relative liver wt. of the tumor-inoculated mice significantly increased as compared to that of the normal mice due to the tumor metastasis, as verified by the hematoxylin-eosin staining pathological study in the LLC experiment. The relative liver wt. of the WECS-administered mice significantly decreased relative to that of the control mice in both the LLC and B16 experiments. WECS showed a strong cytotoxicity against LLC and B16 cells, while cordycepin (3'-deoxyadenosine), an active component of WECS, was not cytotoxic against these cells. These findings suggest that WECS has an anti-metastatic activity that is probably due to components other than cordycepin.








Cordyceps sinensis Health Supplement Enhances Recovery from Taxol-Induced Leukopenia
Wei-Chung Liu, Wei-Ling Chuang, [...], and Chi-Shiun Chiang
Additional article information
Abstract
This study aimed to evaluate the ability of the health food supplement Cordyceps sinensis (CS) to ameliorate suppressive effects of chemotherapy on bone marrow function as a model for cancer treatment Mice were treated with Taxol (17 mg/kg body wt) one day before oral administration of a hot-water extract of CS (50 mg/kg daily) that was given daily for 3 weeks. White blood cell counts in peripheral blood of mice receiving Taxol were at 50% of normal levels on day 28 but had recovered completely in mice treated with CS. In vitro assays showed that CS enhanced the colony-forming ability of both granulocyte macrophage colony forming unit (GM-CFU) and osteogenic cells from bone marrow preparations and promoted the differentiation of bone marrow mesenchymal stromal cells into adipocytes, alkaline phosphatase–positive osteoblasts, and bone tissue. This result could be attributed to enhanced expression of Cbfa1 (core binding factor a) and BMP-2 (bone morphogenetic protein) with concurrent suppression of ODF (osteoclast differentiation factor/RANK [receptor activator of NF-κB]) ligand. In summary, CS enhances recovery of mice from leukopenia caused by Taxol treatment. It appears to do so by protecting both hematopoietic progenitor cells directly and the bone marrow stem cell niche through its effects on osteoblast differentiation.








Cordyceps sinensis protects against liver and heart injuries in a rat model of chronic kidney disease: a metabolomic analysis
Xia Liu, Fang Zhong, [...], and Nai-xia Zhang
Abstract
To test the hypothesis that the traditional Chinese medicine Cordyceps sinensis could improve the metabolic function of extrarenal organs to achieve its anti-chronic kidney disease (CKD) effects.
Methods:
Male SD rats were divided into CKD rats (with 5/6-nephrectomy), CKD rats treated with Cordyceps sinensis (4 mg•kg-1•d-1, po), and sham-operated rats. After an 8-week treatment, metabolites were extracted from the hearts and livers of the rats, and then subjected to 1H-NMR-based metabolomic analysis.
Results:
Oxidative stress, energy metabolism, amino acid and protein metabolism and choline metabolism were considered as links between CKD and extrarenal organ dysfunction. Within the experimental period of 8 weeks, the metabolic disorders in the liver were more pronounced than in the heart, suggesting that CKD-related extrarenal organ dysfunctions occurred sequentially rather than simultaneously. Oral administration of Cordyceps sinensis exerted statistically significant rescue effects on the liver and heart by reversely regulating levels of those metabolites that are typically perturbed in CKD.
Conclusion:
Oral administration of Cordyceps sinensis significantly attenuates the liver and heart injuries in CKD rats. The 1H NMR-based metabolomic approach has provided a systematic view for understanding of CKD and the drug treatment, which can also be used to elucidate the mechanisms of action of other traditional Chinese medicines.






Cardiovascular protection and antioxidant activity of the extracts from the mycelia of Cordyceps sinensis act partially via adenosine receptors.
Yan XF1, Zhang ZM, Yao HY, Guan Y, Zhu JP, Zhang LH, Jia YL, Wang RW.
Author information
Abstract
Mycelia of cultured Cordyceps sinensis (CS) is one of the most common substitutes for natural CS and was approved for arrhythmia in China. However, the role of CS in ameliorating injury during ischemia-reperfusion (I/R) is still unclear. We examined effects of extracts from CS on I/R and investigated the possible mechanisms. Post-ischemic coronary perfusion pressure, ventricular function, and coronary flow were measured using the Langendorff mouse heart model. Oxidative stress of cardiac homogenates was performed using an ELISA. Our results indicate that CS affords cardioprotection possibly through enhanced adenosine receptor activation. Cardioprotection was demonstrated by reduced post-ischemic diastolic dysfunction and improved recovery of pressure development and coronary flow. Treatment with CS largely abrogates oxidative stress and damage in glucose- or pyruvate-perfused hearts. Importantly, observed reductions in oxidative stress [glutathione disulfide (GSSG)]/[GSSG + glutathione] and [malondialdehyde (MDA)]/[superoxide dismutase + MDA] ratios as well as the resultant damage upon CS treatment correlate with functional markers of post-ischemic myocardial outcome. These effects of CS were partially blocked by 8-ρ-sulfophenyltheophylline, an adenosine receptor antagonist. Our results demonstrate a suppressive role of CS in ischemic contracture. Meanwhile, the results also suggest pre-ischemic adenosine receptor activation may be involved in reducing contracture in hearts pretreated with CS.
Copyright © 2012 John Wiley & Sons, Ltd.







Cordycepin prevents hyperlipidemia in hamsters fed a high-fat diet via activation of AMP-activated protein kinase.
Guo P1, Kai Q, Gao J, Lian ZQ, Wu CM, Wu CA, Zhu HB.
Author information
Abstract
Hyperlipidemia is a major risk factor for cardiovascular diseases. In this study, we investigated the potential effects of cordycepin (3'-deoxyadenosine), a bioactive component of the fungus Cordyceps militaris, on hyperlipidemia. We found that in male Syrian golden hamsters fed a high-fat diet (HFD), daily administration of cordycepin effectively reduced the accumulation of serum total cholesterol (TC), triglycerides (TG), and low-density lipoprotein cholesterol (LDL-c) and suppressed HFD-associated increases in relative retroperitoneal fat. It also increased the levels of phospho-AMP-activated protein kinase (AMPK) and phospho-acetyl-CoA carboxylase (phospho-ACC) in liver and retroperitoneal adipose tissues. In HepG2 cells, cordycepin stimulated robust concentration- and time-dependent AMPK activation that correlated with the activation of ACC and the suppression of lipid biosynthesis. However, pretreatment with compound C, a specific inhibitor of AMPK, substantially abolished the effects of cordycepin on AMPK activation and lipid biosynthesis inhibition. These results indicate that cordycepin prevents hyperlipidemia via activation of AMPK. Experiments on abnormal metabolic mice indicated that cordycepin can also improve insulin sensitivity effectively.








Hypocholesterolemic Effect of Hot-Water Extract from Mycelia of Cordyceps sinensis
Jong-Ho Koh, Jin-Man Kim, Un-Jae Chang, Hyung-Joo Suh
Author information

Abstract
This study was conducted to investigate the hypocholesterolemic effect of the hot-water fraction (HW) from cultured mycelia of Cordyceps sinensis in a 5 l fermenter. The composition of HW was mainly carbohydrate (83.9%) and protein (11.8%) on a dry basis, and the carbohydrate of HW consisted of glucose, mannose, galactose, and arabinose in the molecular ratio of 1.0 : 0.8 : 0.5 : 0.1, respectively. In mice fed a cholesterol-free diet and those fed a cholesterol-enriched diet, body and liver weights were not significantly different from those of the controls. The serum total cholesterol (TC) of all mice groups administered HW (150 and 300 mg/kg/d, respectively) with the cholesterol-enriched diet decreased more than in the control group. Among the mice fed the cholesterol-enriched diet, HW also increased the high-density lipoprotein (HDL) cholesterol level, but decreased the very low-density lipoprotein plus low-density lipoprotein (VLDL+LDL) cholesterol level. The changes in HDL- and VLDL+LDL-cholesterol levels consequently decreased the atherogenic value. The results indicate that HW in rats administered a cholesterol-enriched diet decreased the plasma cholesterol level. The 300 mg/kg dose had a significant effect on the serum TC level.








Cordyceps sinensis as an immunomodulatory agent.
Kuo YC1, Tsai WJ, Shiao MS, Chen CF, Lin CY.
Author information
Abstract
Effects of various fractions of methanol extracts from fruiting bodies of Cordyceps sinensis on the lymphoproliferative response, natural killer (NK) cell activity, and phytohemagglutinin (PHA) stimulated interleukin-2 (IL-2) and tumor necrosis factor-alpha (TNF-alpha) production on human mononuclear cells (HMNC) were studied. Two of the 15 column fractions (CS-36-39 and CS-48-51) significantly inhibited the blastogenesis response (IC50 = 71.0 +/- 3.0 and 21.7 +/- 2.0 micrograms/ml, respectively), NK cell activity (IC50 = 25.0 +/- 2.5 and 12.9 +/- 5.8 micrograms/ml, respectively) and IL-2 production of HMNC stimulated by PHA (IC50 = 9.6 +/- 2.3 and 5.5 +/- 1.6 micrograms/ml, respectively). TNF-alpha production in HMNC cultures was also blocked by CS-36-39 and CS-48-51 (IC50 = 2.7 +/- 1.0 and 12.5 +/- 3.8 micrograms/ml, respectively). These results indicated that neither CS-36-39 nor CS-48-51 was cytotoxic on HMNC, and that immunosuppressive ingredients are contained in Cordyceps sinensis.







Lead poisoning caused by contaminated Cordyceps, a Chinese herbal medicine: two case reports.
Wu TN1, Yang KC, Wang CM, Lai JS, Ko KN, Chang PY, Liou SH.
Author information
Abstract
Two cases of lead poisoning, caused by the Chinese herbal medicine Cordyceps, were reported to the Department of Health in a laboratory-based blood lead surveillance program. Such unusual cases of lead poisoning have not been previously reported. These two patients took Cordyceps herbal medicine for treatment of underlying diseases. Loss of appetite and anemic signs of lead poisoning were manifested in one patient with a blood lead level of 130 microg/dl, while the other patient was asymptomatic with a blood lead level of 46 microg/dl. The lead content in the Cordyceps powder was found to be as high as 20 000 ppm. After cessation of intake in the asymptomatic patient, and cessation of intake and treatment with chelating agents in the symptomatic patient, the blood lead levels returned to normal range. This report raises concerns about lead poisoning from unusual herbal medicine worldwide.






Reduction of depression and anxiety by 4 weeks Hericium erinaceus intake.
Nagano M1, Shimizu K, Kondo R, Hayashi C, Sato D, Kitagawa K, Ohnuki K.
Author information
Abstract
Hericium erinaceus, a well known edible mushroom, has numerous biological activities. Especially hericenones and erinacines isolated from its fruiting body stimulate nerve growth factor (NGF) synthesis, which expects H. erinaceus to have some effects on brain functions and autonomic nervous system. Herein, we investigated the clinical effects of H. erinaceus on menopause, depression, sleep quality and indefinite complaints, using the Kupperman Menopausal Index (KMI), the Center for Epidemiologic Studies Depression Scale (CES-D), the Pittsburgh Sleep Quality Index (PSQI), and the Indefinite Complaints Index (ICI). Thirty females were randomly assigned to either the H. erinaceus (HE) group or the placebo group and took HE cookies or placebo cookies for 4 weeks. Each of the CES-D and the ICI score after the HE intake was significantly lower than that before. In two terms of the ICI, "insentive" and "palpitatio", each of the mean score of the HE group was significantly lower than the placebo group. "Concentration", "irritating" and "anxious" tended to be lower than the placebo group. Our results show that HE intake has the possibility to reduce depression and anxiety and these results suggest a different mechanism from NGF-enhancing action of H. erinaceus.







Neurotrophic properties of the Lion's mane medicinal mushroom, Hericium erinaceus (Higher Basidiomycetes) from Malaysia.
Lai PL1, Naidu M, Sabaratnam V, Wong KH, David RP, Kuppusamy UR, Abdullah N, Malek SN.
Author information
Abstract
Neurotrophic factors are important in promoting the growth and differentiation of neurons. Nerve growth factor (NGF) is essential for the maintenance of the basal forebrain cholinergic system. Hericenones and erinacines isolated from the medicinal mushroom Hericium erinaceus can induce NGF synthesis in nerve cells. In this study, we evaluated the synergistic interaction between H. erinaceus aqueous extract and exogenous NGF on the neurite outgrowth stimulation of neuroblastoma-glioma cell NG108-15. The neuroprotective effect of the mushroom extract toward oxidative stress was also studied. Aqueous extract of H. erinaceus was shown to be non-cytotoxic to human lung fibroblast MRC-5 and NG108-15 cells. The combination of 10 ng/mL NGF with 1 μg/mL mushroom extract yielded the highest percentage increase of 60.6% neurite outgrowth. The extract contained neuroactive compounds that induced the secretion of extracellular NGF in NG108-15 cells, thereby promoting neurite outgrowth activity. However, the H. erinaceus extract failed to protect NG108-15 cells subjected to oxidative stress when applied in pre-treatment and co-treatment modes. In conclusion, the aqueous extract of H. erinaceus contained neuroactive compounds which induced NGF-synthesis and promoted neurite outgrowth in NG108-15 cells. The extract also enhanced the neurite outgrowth stimulation activity of NGF when applied in combination. The aqueous preparation of H. erinaceus had neurotrophic but not neuroprotective activities.









Improving effects of the mushroom Yamabushitake (Hericium erinaceus) on mild cognitive impairment: a double-blind placebo-controlled clinical trial.
Mori K1, Inatomi S, Ouchi K, Azumi Y, Tuchida T.
Author information
Abstract
A double-blind, parallel-group, placebo-controlled trial was performed on 50- to 80-year-old Japanese men and women diagnosed with mild cognitive impairment in order to examine the efficacy of oral administration of Yamabushitake (Hericium erinaceus), an edible mushroom, for improving cognitive impairment, using a cognitive function scale based on the Revised Hasegawa Dementia Scale (HDS-R). After 2 weeks of preliminary examination, 30 subjects were randomized into two 15-person groups, one of which was given Yamabushitake and the other given a placebo. The subjects of the Yamabushitake group took four 250 mg tablets containing 96% of Yamabushitake dry powder three times a day for 16 weeks. After termination of the intake, the subjects were observed for the next 4 weeks. At weeks 8, 12 and 16 of the trial, the Yamabushitake group showed significantly increased scores on the cognitive function scale compared with the placebo group. The Yamabushitake group's scores increased with the duration of intake, but at week 4 after the termination of the 16 weeks intake, the scores decreased significantly. Laboratory tests showed no adverse effect of Yamabushitake. The results obtained in this study suggest that Yamabushitake is effective in improving mild cognitive impairment.
(c) 2008 John Wiley & Sons, Ltd.
(ci)









Neurohealth Properties of Hericium erinaceus Mycelia Enriched with Erinacines.
Li IC1, Lee LY1, Tzeng TT2, Chen WP1, Chen YP1, Shiao YJ2, Chen CC1,3,4,5.
Author information
Abstract
Hericium erinaceus, an ideal culinary-medicinal mushroom, has become a well-established candidate in promoting positive brain and nerve health-related activities by inducing the nerve growth factor from its bioactive ingredient. Among its active compounds, only erinacine A has confirmed pharmacological actions in the central nervous system in rats. Hence, this review has summarized the available information on the neurohealth properties of H. erinaceus mycelia enriched with erinacines, which may contribute to further research on the therapeutic roles of these mycelia. The safety of this mushroom has also been discussed. Although it has been difficult to extrapolate the in vivo studies to clinical situations, preclinical studies have shown that there can be improvements in ischemic stroke, Parkinson's disease, Alzheimer's disease, and depression if H. erinaceus mycelia enriched with erinacines are included in daily meals.







Anticancer potential of Hericium erinaceus extracts against human gastrointestinal cancers.
Li G1, Yu K1, Li F1, Xu K1, Li J1, He S2, Cao S3, Tan G4.
Author information
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE:
Hericium is a genus of mushrooms (fungus) in the Hericiaceae family. Hericium erinaceus (HE) has been used for the treatment of digestive diseases for over 2000 years in China. HE possesses many beneficial functions such as anticancer, antiulcer, antiinflammation and antimicrobial effects, immunomodulation and other activities. The aim of the studies was to evaluate the anticancer efficacy of two extracts (HTJ5 and HTJ5A) from the culture broth of HE against three gastrointestinal cancers such as liver, colorectal and gastric cancers in both of in vitro of cancer cell lines and in vivo of tumor xenografts and discover the active compounds.
MATERIALS AND METHODS:
Two HE extracts (HTJ5 and HTJ5A) were used for the studies. For the study of chemical constituents, the HTJ5 and HTJ5A were separated using a combination of macroporous resin with silica gel, HW-40 and LH-20 chromatography then purified by semipreparative high-performance liquid chromatography (HPLC) and determined by nuclear magnetic resonance (NMR) spectra. For the in vitro cytotoxicity studies, HepG2 and Huh-7 liver, HT-29 colon, and NCI-87 gastric cancer cell lines were used and MTT assay was performed to determine the in vitro cytotoxicity. For in vivo antitumor efficacy and toxicity studies, tumor xenograft models of SCID mice bearing liver cancer HepG2 and Huh-7, colon cancer HT-29 and gastric cancer NCI-87 subcutaneously were used and the mice were treated with the vehicle control, HTJ5 and HTJ5A orally (500 and 1000 mg/kg/day) and compared to 5-fluorouraci (5-FU) at the maximum tolerated dose (MTD, 25-30 mg/kg/day) intraperitoneally daily for 5 days when the tumors reached about 180-200 mg (mm(3)). Tumor volumes and body weight were measured daily during the first 10 days and 2-3 times a week thereafter to assess the tumor growth inhibition, tumor doubling time, partial and complete tumor response and toxicity.
RESULTS:
Twenty-two compounds were obtained from the fractions of HTJ5/HTJ5A including seven cycli dipeptides, five indole, pyrimidines, amino acids and derivative, three flavones, one anthraquinone, and six small aromatic compounds. HTJ5 and HTJ5A exhibited concentration-dependent cytotoxicity in vitro against liver cancer HepG2 and Huh-7, colon cancer HT-29, and gastric cancer NCI-87 cells with the IC50 in 2.50±0.25 and 2.00±0.25, 0.80±0.08 and 1.50±0.28, 1.25±0.06 and 1.25±0.05, and 5.00±0.22 and 4.50±0.14 mg/ml; respectively. For in vivo tumor xenograft studies, HTJ5 and HTJ5A showed significantly antitumor efficacy against all four xenograft models of HepG2, Huh-7, HT-29 and NCI-87 without toxicity to the host. Furthermore, HTJ5 and HTJ5A are more effective than that of 5-FU against the four tumors with less toxicity.
CONCLUSION:
HE extracts (HTJ5 and HTJ5A) are active against liver cancer HepG2 and Huh-7, colon cancer HT-29 and gastric cancer NCI-87 cells in vitro and tumor xenografts bearing in SCID mice in vivo. They are more effective and less toxic compared to 5-FU in all four in vivo tumor models. The compounds have the potential for development into anticancer agents for the treatment of gastrointestinal cancer used alone and/or in combination with clinical used chemotherapeutic drugs. However, further studies are required to find out the active chemical constituents and understand the mechanism of action associated with the super in vivo anticancer efficacy. In addition, future studies are needed to confirm our preliminary results of in vivo synergistic antitumor efficacy in animal models of tumor xenografts with the combination of HE extracts and clinical used anticancer drugs such as 5-FU, cisplatin and doxurubicin for the treatment of gastrointestinal cancers.
Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.





Gastroprotective Effects of Lion's Mane Mushroom Hericium erinaceus (Bull.:Fr.) Pers. (Aphyllophoromycetideae) Extract against Ethanol-Induced Ulcer in Rats.
Wong JY1, Abdulla MA, Raman J, Phan CW, Kuppusamy UR, Golbabapour S, Sabaratnam V.
Author information
Abstract
Hericium erinaceus is a famous tonic in oriental medicine. The gastroprotective effects of aqueous extract of H. erinaceus against ethanol-induced ulcers in Sprague Dawley rats were investigated. The possible involvements of lipid peroxidation, superoxide dismutase, and catalase were also investigated. Acute toxicity study was performed. The effects of aqueous extract of H. erinaceus on the ulcer areas, ulcer inhibition, gastric wall mucus, gross and histological gastric lesions, antioxidant levels, and malondialdehyde (MDA) contents were evaluated in ethanol-induced ulcer in vivo. In acute toxicity study, a high dose of 5 g/kg did not manifest any toxicological signs in rats. The extract promoted ulcer protection as ascertained by a significant reduction of the ulcer area. Furthermore, it exhibited a significant protection activity against gastric mucosal injury by preventing the depletion of antioxidant enzymes. The level of MDA was also limited in rat stomach tissues when compared with the ulcer control group. Immunohistochemistry showed upregulation of HSP70 protein and downregulation of BAX protein in rats pretreated with the extract. The aqueous extract of H. erinaceus protected gastric mucosa in our in vivo model. It is speculated that the bioactive compounds present in the extract may play a major role in gastroprotective activity.







Anti-inflammatory activity of mycelial extracts from medicinal mushrooms.
Geng Y1, Zhu S1, Lu Z2, Xu H2, Shi JS1, Xu ZH3.
Author information
Abstract
Medicinal mushrooms have been essential components of traditional Chinese herbal medicines for thousands of years, and they protect against diverse health-related conditions. The components responsible for their anti-inflammatory activity have yet to be fully studied. This study investigates the anti-inflammatory activity of n-hexane, chloroform, ethyl acetate, and methanol extracts of mycelia in submerged culture from 5 commercially available medicinal mushrooms, namely Cephalosporium sinensis, Cordyceps mortierella, Hericium erinaceus, Ganoderma lucidum, and Armillaria mellea. MTT colorimetric assay was applied to measure the cytotoxic effects of different extracts. Their anti-inflammatory activities were evaluated via inhibition against production of lipopolysaccharide (LPS)-induced nitric oxide (NO) in murine macrophage-like cell line RAW264.7 cells. Of the 20 extracts, n-hexane, chloroform, ethyl acetate, and methanol extracts from C. sinensis, C. mortierella, and G. lucidum; chloroform extracts from H. erinaceus and A. mellea; and ethyl acetate extracts from A. mellea at nontoxic concentrations (<300 μg/mL) dose-dependently inhibited LPS-induced NO production. Among them, the chloroform extract from G. lucidum was the most effective inhibitor, with the lowest half maximal inhibitory concentration (64.09 ± 6.29 μg/mL) of the LPS-induced NO production. These results indicate that extracts from medicinal mushrooms exhibited anti-inflammatory activity that might be attributable to the inhibition of NO generation and can therefore be considered a useful therapeutic and preventive approach to various inflammation-related diseases.







The influence of Hericium erinaceus extract on myelination process in vitro.
Kolotushkina EV1, Moldavan MG, Voronin KY, Skibo GG.
Author information
Abstract
Myelin sheaths, wrapping axons, perform the following important functions: support, protection, feeding and isolation. Injury of myelin compact structure leads to an impairment and severe illness of the nerve system. Exact mechanisms underlying the myelination process and myelin sheaths damage have not established yet. Therefore search for substances, which provide regulatory and protective effects on the normal myelination as well as stimulating action on the remyelination after myelin damage, is of special interest. Recently it was shown that extract from mushroom Hericium erinaceus had activating action on the nerve tissue. So the aim of the present work was to study an influence of an extract from H. erinaceus on the cerebellar cells and the process of myelination in vitro. Obtained data revealed the normal growth of the nerve and glial cells with extract at cultivating. No pathologic or toxic action of the extract has been found. The cell ultrastructure was intact and similar to that observed in vivo. The process of myelination in the presence of the extract began earlier as compared to controls and was characterised by a higher rate. Thus, extract of H. erinaceus promoted normal development of cultivated cerebellar cells and demonstrated a regulatory effect on the process of myelin genesis process in vitro.







Improvement of cognitive functions by oral intake of Hericium erinaceus.
Saitsu Y1, Nishide A2, Kikushima K3, Shimizu K4, Ohnuki K1.
Author information
Abstract
Hericium erinaceus has been recognized as medical mushroom since ancient time, but its scientific evidence for human health has been still uncertain. In this study, we tested a randomized, double-blind, placebo-controlled parallel-group comparative study to evaluate the improvement of the cognitive functions by taking supplements containing fruiting body of H. erinaceus for 12 weeks. We performed three kinds of tests: Mini Mental State Examination (MMSE), Benton visual retention test, and Standard verbal paired-associate learning test (S-PA). MMSE alone showed that oral intake of H. erinaceus significantly improved cognitive functions and prevented from the deterioration. We speculate that various chemical compounds, including hericenones, in the mushroom have multiple effects to the brain neural networks and improve cognitive functions. Oral intake of H.erinaceus is safe and convenient method for dementia prevention so far.







Reduction of depression and anxiety by 4 weeks Hericium erinaceus intake.
Nagano M1, Shimizu K, Kondo R, Hayashi C, Sato D, Kitagawa K, Ohnuki K.
Author information
Abstract
Hericium erinaceus, a well known edible mushroom, has numerous biological activities. Especially hericenones and erinacines isolated from its fruiting body stimulate nerve growth factor (NGF) synthesis, which expects H. erinaceus to have some effects on brain functions and autonomic nervous system. Herein, we investigated the clinical effects of H. erinaceus on menopause, depression, sleep quality and indefinite complaints, using the Kupperman Menopausal Index (KMI), the Center for Epidemiologic Studies Depression Scale (CES-D), the Pittsburgh Sleep Quality Index (PSQI), and the Indefinite Complaints Index (ICI). Thirty females were randomly assigned to either the H. erinaceus (HE) group or the placebo group and took HE cookies or placebo cookies for 4 weeks. Each of the CES-D and the ICI score after the HE intake was significantly lower than that before. In two terms of the ICI, "insentive" and "palpitatio", each of the mean score of the HE group was significantly lower than the placebo group. "Concentration", "irritating" and "anxious" tended to be lower than the placebo group. Our results show that HE intake has the possibility to reduce depression and anxiety and these results suggest a different mechanism from NGF-enhancing action of H. erinaceus.







Hericium erinaceus Improves Mood and Sleep Disorders in Patients Affected by Overweight or Obesity: Could Circulating Pro-BDNF and BDNF Be Potential Biomarkers?
Vigna L1, Morelli F1, Agnelli GM1, Napolitano F2, Ratto D3, Occhinegro A3, Di Iorio C3, Savino E4, Girometta C4, Brandalise F5, Rossi P3.
Author information
Abstract
Epidemiological data indicate that subjects affected by obesity have an increased risk of developing mood disorders. The relationship between obesity and mood disorders is bidirectional. We assessed whether a Hericium erinaceus treatment improved depression, anxiety, sleep, and binge eating disorders after 8 weeks of supplementation in subjects affected by overweight or obesity under a low calorie diet regimen. Looking for a possible clinical biomarker, we assessed the serum balance between brain-derived neurotrophic factor (BDNF) and its precursor pro-BDNF before and after H. erinaceus supplementation. Seventy-seven volunteers affected by overweight or obesity were recruited at the offices of the Department of Preventive Medicine, Luigi Devoto Clinic of Work, Obesity Centre, at the IRCCS Foundation Policlinico Hospital of Milan (Italy). Patients were recruited only if they had a mood and/or sleep disorder and/or were binge eating as evaluated through self-assessment questionnaires. We used two different enzyme-linked immunosorbent assays kits to discriminate circulating levels of pro-BDNF and BDNF. Eight weeks of oral H. erinaceus supplementation decreased depression, anxiety, and sleep disorders. H. erinaceus supplementation improved mood disorders of a depressive-anxious nature and the quality of the nocturnal rest. H. erinaceus increased circulating pro-BDNF levels without any significant change in BDNF circulating levels.







The Neuroprotective Effect of Hericium erinaceus Extracts in Mouse Hippocampus after Pilocarpine-Induced Status Epilepticus.
Jang HJ1, Kim JE2, Jeong KH3,4, Lim SC5, Kim SY6, Cho KO7,8.
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Abstract
Hericium erinaceus (HE), a culinary-medicinal mushroom, has shown therapeutic potential in many brain diseases. However, the role of HE in status epilepticus (SE)-mediated neuronal death and its underlying mechanisms remain unclear. We investigated the neuroprotective effects of HE using a pilocarpine-induced SE model. Male C57BL/6 mice received crude extracts of HE (60 mg/kg, 120 mg/kg, or 300 mg/kg, p.o.) for 21 d from 14 d before SE to 6 d after SE. At 7 d after SE, cresyl violet and immunohistochemistry of neuronal nuclei revealed improved hippocampal neuronal survival in animals treated with 60 mg/kg and 120 mg/kg of HE, whereas those treated with 300 mg/kg of HE showed similar neuronal death to that of vehicle-treated controls. While seizure-induced reactive gliosis, assessed by immunohistochemistry, was not altered by HE, the number of hippocampal cyclooxygenase 2 (COX2)-expressing cells was significantly reduced by 60 and 120 mg/kg of HE. Triple immunohistochemistry demonstrated no overlap of COX2 labeling with Ox42, in addition to a decrease in COX2/GFAP-co-immunoreactivity in the group treated with 60 mg/kg HE, suggesting that the reduction of COX2 by HE promotes neuroprotection after SE. Our findings highlight the potential application of HE for preventing neuronal death after seizures.







Anti-obesity activity of Yamabushitake (Hericium erinaceus) powder in ovariectomized mice, and its potentially active compounds.
Hiraki E1, Furuta S1, Kuwahara R1, Takemoto N1, Nagata T1, Akasaka T2, Shirouchi B3, Sato M3, Ohnuki K4, Shimizu K5.
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Abstract
Hericium erinaceus (H. erinaceus) improves the symptoms of menopause. In this study, using ovariectomized mice as a model of menopause, we investigated the anti-obesity effect of this mushroom in menopause. Mice fed diets containing H. erinaceus powder showed significant decreases in the amounts of fat tissue, plasma levels of total cholesterol, and leptin. To determine the mechanism, groups of mice were respectively fed a diet containing H. erinaceus powder, a diet containing ethanol extract of H. erinaceus, and a diet containing a residue of the extract. As a result, H. erinaceus powder was found to increase fecal lipid levels in excreted matter. Further in vitro investigation showed that ethanol extract inhibited the activity of lipase, and four lipase-inhibitory compounds were isolated from the extract: hericenone C, hericenone D, hericenone F, and hericenone G. In short, we suggest that H. erinaceus has an anti-obesity effect during menopause because it decreases the ability to absorb lipids.







Nerve growth factor-inducing activity of Hericium erinaceus in 1321N1 human astrocytoma cells.
Mori K1, Obara Y, Hirota M, Azumi Y, Kinugasa S, Inatomi S, Nakahata N.
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Abstract
Neurotrophic factors are essential to maintain and organize neurons functionally; thereby neurotrophic factor-like substances or their inducers are expected to be applied to the treatment of neurodegenerative diseases such as Alzheimer's disease. In the present study, we firstly examined the effects of ethanol extracts of four edible mushrooms, Hericium erinaceus (Yamabushitake), Pleurotus eryngii (Eringi), Grifola frondosa (Maitake), and Agaricus blazei (Himematsutake), on nerve growth factor (NGF) gene expression in 1321N1 human astrocytoma cells. Among the four mushroom extracts, only H. erinaceus extract promoted NGF mRNA expression in a concentration-dependent manner. In addition, secretion of NGF protein from 1321N1 cells was enhanced by H. erinaceus extracts, and the conditioned medium of 1321N1 cells incubated with H. erinaceus extract enhanced the neurite outgrowth of PC12 cells. However, hericenones C, D and E, constituents of H. erinaceus, failed to promote NGF gene expression in 1321N1 cells. The enhancement of NGF gene expression by H. erinaceus extracts was inhibited by the c-jun N-terminal kinase (JNK) inhibitor SP600125. In addition, H. erinaceus extracts induced phosphorylation of JNK and its downstream substrate c-Jun, and increased c-fos expression, suggesting that H. erinaceus promotes NGF gene expression via JNK signaling. Furthermore we examined the efficacy of H. erinaceus in vivo. ddY mice given feed containing 5% H. erinaceus dry powder for 7 d showed an increase in the level of NGF mRNA expression in the hippocampus. In conclusion, H. erinaceus contains active compounds that stimulate NGF synthesis via activation of the JNK pathway; these compounds are not hericenones.








Yamabushitake mushroom (Hericium erinaceus) improved lipid metabolism in mice fed a high-fat diet.
Hiwatashi K1, Kosaka Y, Suzuki N, Hata K, Mukaiyama T, Sakamoto K, Shirakawa H, Komai M.
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Abstract
The effects of dietary Yamabushitake mushroom (Hericium erinaceus) on lipid metabolism were examined. C57BL/6J mice were fed a high-fat diet containing hot-water extract (HW-E) and an ethanol extract (EtOH-E) of Yamabushitake mushroom. Administration of HW-E or EtOH-E with a high-fat diet for 28 d resulted in a significant decrease in body weight gain, fat weight, and serum and hepatic triacylglycerol levels. Our in vitro experiments indicated that EtOH-E acts as an agonist of peroxisome proliferator-activated receptor alpha (PPARalpha). Quantitative analyses of hepatic mRNA levels revealed that EtOH-E administration resulted in up-regulation of mRNA for a number of PPARalpha-regulating genes in spite of the fact that the gene expression of PPARalpha did not change. These results suggest that EtOH-E improves lipid metabolism in mice fed a high-fat diet, and that these effects were mediated by modulation of lipid metabolic gene expression, at least in part via activation of PPARalpha.






Structures, biological activities, and industrial applications of the polysaccharides from Hericium erinaceus (Lion's Mane) mushroom: A review.
He X1, Wang X2, Fang J2, Chang Y3, Ning N3, Guo H3, Huang L4, Huang X3, Zhao Z2.
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Abstract
Hericium erinaceus (Bull.) Pers., also known as Yamabushitake, Houtou and Lion's Mane, is capable of fortifying the spleen and nourishing the stomach, tranquilizing the mind, and fighting cancer. Over the past decade, it has been demonstrated that H. erinaceus polysaccharides possess various promising bioactivities, including antitumor and immunomodulation, anti-gastric ulcer, neuroprotection and neuroregeneration, anti-oxidation and hepatoprotection, anti-hyperlipidemia, anti-hyperglycemia, anti-fatigue and anti-aging. The purpose of the present review is to provide systematically reorganized information on extraction and purification, structure characteristics, biological activities, and industrial applications of H. erinaceus polysaccharides to support their therapeutic potentials and sanitarian functions.
Copyright © 2017 Elsevier B.V. All rights reserved.









Abstract
Maitake α-glucan, YM-2A, isolated from Grifola frondosa, has been characterized as a highly α-1,6-branched α-1,4 glucan. YM-2A has been shown to possess an anti-virus effect in mice; however, it does not directly inhibit growth of the virus in vitro, indicating that the anti-virus effect of YM-2A might be associated with modulation of the host immune system. In this study, we found that oral administration of YM-2A could inhibit tumor growth and improve survival rate in two distinct mouse models of colon-26 carcinoma and B16 melanoma. Orally administered YM-2A enhanced antitumor immune response by increasing INF-γ-expressing CD4+ and CD8+ cells in the spleen and INF-γ-expressing CD8+ cells in tumor-draining lymph nodes. In vitro study showed that YM-2A directly activated splenic CD11b+ myeloid cells, peritoneal macrophages and bone marrow-derived dendritic cells, but did not affect splenic CD11b- lymphocytes or colon-26 tumor cells. YM-2A is more slowly digested by pancreatic α-amylase than are amylopectin and rabbit liver glycogen, and orally administered YM-2A enhanced the expression of MHC class II and CD86 on dendritic cells and the expression of MHC class II on macrophages in Peyer’s patches. Furthermore, in vitro stimulation of YM-2A increased the expression of pro-inflammatory cytokines in Peyer’s patch CD11c+ cells. These results suggest that orally administered YM-2A can activate dendritic cells and macrophages in Peyer’s patches, inducing systemic antitumor T-cell response. Thus, YM-2A might be a candidate for an oral therapeutic agent in cancer immunotherapy.






Induction Effect to Apoptosis by Maitake Polysaccharide: Synergistic Effect of Its Combination With Vitamin C in Neuroglioma Cell.
Duan L1,2,3, Wu XL3, Zhao F1,2,4, Zeng R1,2,3, Yang KH1,2.
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Abstract
Polysaccharide extracted from the Maitake mushroom (MP) is considered as a potential anticancer agent. The present study was performed to investigate the cytotoxic effects of MP and vitamin C (VC) alone and in combination on the viability of human neuroglioma M059 K cells in vitro. A combination of MP (1.0 mg/mL) and VC (0.4 mmol/L) led to a 53.10% reduction in cell viability and this treatment induced cell cycle arrest at the G2/M phase, and apoptosis occurred in 38.54% of the cells. Results of Hoechst 33258 staining and Western blot showed apoptotic cells appeared and changes in the expression of apoptosis-related proteins (upregulation of Bax and caspase-3, downregulation of Bcl-2, and activation of poly-(ADP-ribose)-polymerase). Moreover, the activities of caspase-3, caspase-8, and caspase-9 were enhanced in M059 K cells. The inhibiting effect of combined treatment with MP and VC on M059 K cells indicates the mechanism of anticancer activity involved induction of cell apoptosis.







Monitoring of immune responses to a herbal immuno-modulator in patients with advanced colorectal cancer.
Chen X1, Hu ZP, Yang XX, Huang M, Gao Y, Tang W, Chan SY, Dai X, Ye J, Ho PC, Duan W, Yang HY, Zhu YZ, Zhou SF.
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Abstract
Many herbal medicines are widely used as immuno-modulators in Asian countries. Ganoderma lucidum (Lingzhi) is one of the most commonly used herbs in Asia and preclinical studies have established that the polysaccharide fractions of G. lucidum have potent immuno-modulating effects. However, clinical evidence for this is scanty. The present open-labeled study aimed to evaluate the effects of G. lucidum polysaccharides on selected immune functions in patients with advanced colorectal cancer. Forty-seven patients were enrolled and treated with oral G. lucidum at 5.4 g/day for 12 weeks. Selected immune parameters were monitored using various immunological methods throughout the study. In 41 assessable cancer patients, treatment with G. lucidum tended to increase mitogenic reactivity to phytohemagglutinin, counts of CD3, CD4, CD8 and CD56 lymphocytes, plasma concentrations of interleukin (IL)-2, IL-6 and interferon (IFN)-gamma, and NK activity, whereas plasma concentrations of IL-1 and tumor necrosis factor (TNF)-alpha were decreased. For all of these parameters, no statistical significance was observed when a comparison was conducted between baseline and those values after a 12-week treatment with G. lucidum. The changes of IL-1 were correlated with those for IL-6, IFN-gamma, CD3, CD4, CD8 and NK activity (p<0.05) and IL-2 changes were correlated with those for IL-6, CD8 and NK activity. The results indicate that G. lucidum may have potential immuno-modulating effect in patients with advanced colorectal cancer. Further studies are needed to explore the benefits and safety of G. lucidum in cancer patients.







Probing Lingzhi or Reishi medicinal mushroom Ganoderma lucidum (higher Basidiomycetes): a bitter mushroom with amazing health benefits.
Batra P1, Sharma AK, Khajuria R.
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Abstract
Ganoderma lucidum (Lingzhi or Reishi) is known as a bitter mushroom with remarkable health benefits. The active constituents found in mushrooms include polysaccharides, dietary fibers, oligosaccharides, triterpenoids, peptides and proteins, alcohols and phenols, mineral elements (such as zinc, copper, iodine, selenium, and iron), vitamins, and amino acids. The bioactive components found in the G. lucidum mushroom have numerous health properties to treat diseased conditions such as hepatopathy, chronic hepatitis, nephritis, hypertension, hyperlipemia, arthritis, neurasthenia, insomnia, bronchitis, asthma, gastric ulcers, atherosclerosis, leukopenia, diabetes, anorexia, and cancer. In spite of the voluminous literature available, G. lucidum is used mostly as an immune enhancer and a health supplement, not therapeutically. This review discusses the therapeutic potential of G. luidum to attract the scientific community to consider its therapeutic application where it can be worth pursuing.





Cellular and molecular mechanisms of immuno-modulation by Ganoderma lucidum.
Lin ZB1.
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Abstract
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.







Cancer Prevention and Treatment by Ganoderma, a Mushroom with Medicinal Properties
Yihuai Gao &Shufeng Zhou 

Abstract
Ganoderma, highly ranked in Oriental traditional medicine, has been used as a remedy for many types of chronic diseases, including hepatopathy, type II diabetes, neurasthenia, hypertension, and cancer. Various polysaccharides (i.e., β-D-glucans and glycoproteins) and triterpenoids are the major active constituents present in Ganoderma. In vitro and animal studies have indicated that Ganoderma exhibits cancer-preventive and anticancer activity. Data from a clinical study in cancer patients showed Ganopoly, a crude Ganoderma polysaccharide extract, enhanced host immune function, including increased activity of effector cells such as T lymphocytes, macrophages, and natural killer cells, despite the lack of striking objective antitumor activity. Several clinical studies revealed that treatment of prostate cancer patients with the Ganoderma-containing PC-SPES (a mixture of eight herbal extracts) gave a significant decrease in the prostate-specific antigen levels, which compares favorably with second-line hormonal therapy that has agents such as estrogens and ketoconazole. Currently available data from numerous in vitro and in vivo studies suggest that the cancer-preventive and tumoricidal properties of Ganoderma might be ascribed to its antioxidative and radical-scavenging effects, enhancement of host immune function, induction of cell-cycle arrest and apoptosis, and other biological effects. Although Ganoderma may represent a practical and promising approach for cancer prevention and cancer treatment, further experimental, epidemiological, and clinical studies are needed to identify unrevealed molecular targets, resolve the relationship between Ganoderma intake and cancer risks, and explore the optimum dosing, efficacy, and safety, alone or in combination with chemotherapy/radiotherapy.





Ganoderma lucidum (Reishi) in cancer treatment.
Sliva D1.
Author information
Abstract
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.








Evaluation of antiproliferative activities and action mechanisms of extracts from two species of Ganoderma on tumor cell lines.
Liu YW1, Gao JL, Guan J, Qian ZM, Feng K, Li SP.
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Abstract
The antiproliferative activities on tumoral cells, namely, human breast cancer (MCF-7 and MDA-MB-231), hepatoma (HepG2) and myeloid leukemia (HL-60), of ethanolic extracts from two species of Ganoderma, G. lucidum and G. sinense, were investigated. Though both extracts had certain antiproliferative activities, their chemical characteristics, including nucleosides, triterpenoids and sterols, were significantly different. Their effects on MDA-MB-231 cells were further studied using apoptotic detection and cell cycle analyses. As a result, both had apoptosis induction through the alternation of mitochondrial transmembrane depolarization, though no triterpenoids were detected in ethanolic extract of G. sinense. Furthermore, the two extracts from G. lucidum and G. sinense could arrest cell cycle at different phases. This study showed that ethanol extracts of both G. lucidum and G. sinense have antitumoral proliferation effect through both apoptosis pathway and cell cycle arrest effect, and some other compounds such as sterols and/or nucleosides may contribute to their activity besides triterpenoids.







Triterpenes from the spores of Ganoderma lucidum and their cytotoxicity against meth-A and LLC tumor cells.
Min BS1, Gao JJ, Nakamura N, Hattori M.
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Abstract
Six new highly oxygenated lanostane-type triterpenes, called ganoderic acid gamma (1), ganoderic acid delta (2), ganoderic acid epsilon (3), ganoderic acid zeta (4), ganoderic acid eta (5) and ganoderic acid theta (6), were isolated from the spores of Ganoderma lucidum, together with known ganolucidic acid D (7) and ganoderic acid C2 (8). Their structures of the new triterpenes were determined as (23S)-7beta,15alpha,23-trihydroxy-3,11-dioxolanosta-8, 24(E)-diene-26-oic acid (1), (23S)-7alpha,15alpha23-trihydroxy-3,11-dioxolanosta-8, 24(E)-diene-26-oic acid (2), (23S)-3beta3,7beta, 23-trihydroxy-11,15-dioxolanosta-8,24(E)-diene-26-oic acid (3), (23S)-3beta,23-dihydroxy-7,11,15-trioxolanosta-8, 24(E)-diene-26-oic acid (4), (23S)-3beta,7beta,12beta,23-tetrahydroxy-11,15-dioxolanos ta-8,24(E)-diene-26-oic acid (5) and (23S)-3beta,12beta23-trihydroxy-7,11,15-trioxolanosta-8,24(E )-diene-26-oic acid (6), respectively, by chemical and spectroscopic means, which included the determination of a chiral center in the side chain by a modification of Mosher's method. The cytotoxicity of the compounds isolated from the Ganoderma spores was carried out in vitro against Meth-A and LLC tumor cell lines.








Effect of mycelial culture broth of Ganoderma lucidum on the growth characteristics of human cell lines.
Chung WT1, Lee SH, Kim JD, Park YS, Hwang B, Lee SY, Lee HY.
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Abstract
Two types of purified samples, water-soluble (sample A; M. W, 1.2 x 10(6) dalton) and water-insoluble (sample C; M. W., 1.0 x 10(6) dalton) samples, were obtained through consecutive separation processes from the culture broth of Ganoderma lucidia mycelium. It was found that both samples from the culture broth were very effective in inhibiting the growth of several human cancer cell lines, having a 93-85% growth inhibition on Hep3B, AGS and A549 with the least cytotoxicity on the normal human lung cell line, WRL68 of less than 25% the highest supplementation concentration of 1.0 mg/l. In general, the sample C showed greater inhibition of cancer cell growth than the sample A. The same trend was also observed in antimutagenicity using the Chinese hamster ovary cell line (CHO test) or Salmonella typhimurium (Ames test). The CHO test showed that sample C had higher antimutagenicity on mutagens 4NQO or MMNG than sample A (approximately 40% vs approximately 25%). The percentage of antimutagenicity from the Ames test was lower than that from the CHO test, possibly due to the difference in the sensitivity of mutagens. The water-insoluble sample greatly enhanced the growth of the human T cell line (H9) up to 1 x 10(5) with sample supplementation at 1.0 mg/l concentration from 4.3 x 10(4) without sample supplementation as well as improved the secretion level of both IL-6 and TNF-alpha up to 100 pg/ml from approximately 40 pg/ml without sample supplementation. The kinetics of response to the immune cell growth was illustrated by the response time obtained when the sample concentration was increased. The water-insoluble sample can be used for effectively treating cancer in that it accelerated apoptosis of human carcinoma cells up to 70% compared to less than 50% for the control. The sample also increased the differentiation ratio of HL-60 cells up to 58% after four days of cultivation, compared to 18% in the case of no sample supplementation. These results can be used in implying that the insoluble part of G. lucidium mycelium culture broth must be related to controlling signal transduction, resulting in the regulation of cancer cell growth.







Regression of prostate cancer following administration of Genistein Combined Polysaccharide (GCP), a nutritional supplement: a case report.
Ghafar MA1, Golliday E, Bingham J, Mansukhani MM, Anastasiadis AG, Katz AE.
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Abstract
PURPOSE:
It has been reported that genistein, an isoflavone used in soybeans, has antiprostate cancer effects. Genistein Combined Polysaccharide (GCP trade mark; AMino Up, Sapporo, Japan), a nutritional supplement manufactured in Japan, is composed of genistein and a polysaccharide obtained from basidiomycetes (mycelia) that grows in a variety of mushrooms.
METHODS:
We report a case of a patient with a biopsy proven prostate cancer showing clinical and pathologic evidence of regression following administration of GCP. The patient was enrolled in an Institutional Review Board (IRB)-approved protocol and received GCP for 6 weeks prior to radical prostatectomy.
RESULTS:
The patient's prostate-specific antigen (PSA) decreased from an initial value of 19.7 to 4.2 ng/mL after 44 days of low-dose GCP. No cancer was identified in the radical prostatectomy specimen and no side effects were observed in this patient.
CONCLUSION:
This case suggests that GCP, which has shown potent inhibitory effects against prostate cancer in vitro, may have some potential activity in the treatment and prevention of prostate cancer.







A water-soluble extract from culture medium of Ganoderma lucidum mycelia suppresses the development of colorectal adenomas.
Oka S1, Tanaka S, Yoshida S, Hiyama T, Ueno Y, Ito M, Kitadai Y, Yoshihara M, Chayama K.
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Abstract
A water-soluble extract from a cultured medium of Ganoderma lucidum mycelia (MAK) is one of the G. lucidum extracts that has been reported to show have exhibit cancer-preventive effects in the animal studies. To confirm cancer-preventive effects of MAK, we performed a no-treatment concurrent controlled trial on patients with colorectal adenomas. Patients who were determined to be carrying colorectal adenomas by colonoscopy were enrolled in this study. Patients in the MAK group took MAK (1.5 g/day) for 12 months. Follow-up colonoscopy was performed after 12 months, and the colonoscopists recorded the size, site and macroscopic type of all adenomas. Among 123 patients who enrolled in the MAK group, 96 eligible patients completed the trial. The 102 eligible patients in the no-treatment control group were selected randomly from our department's patients. The changes in the number of adenomas up to 12 months increased to 0.66 +/- 0.10 (mean +/- SE) in the control group, while decreasing in the MAK group to -0.42 +/- 0.10 (p < 0.01). The total size of adenomas increased to 1.73 +/- 0.28 mm in the control group and decreased to -1.40 +/- 0.64 mm in the MAK group (p < 0.01). The resultssuggest that MAK suppresses the development of colorectal adenomas - precancerous lesions of the large bowel.





Ganoderma lucidum (Reishi mushroom) for cancer treatment.
Jin X1, Ruiz Beguerie J, Sze DM, Chan GC.
Abstract
BACKGROUND:
Ganoderma lucidum is a natural medicine that is widely used and recommended by Asian physicians and naturopaths for its supporting effects on immune system. Laboratory research and a handful of preclinical trials have suggested that G. lucidum carries promising anticancer and immunomodulatory properties. The popularity of taking G. lucidum as an alternative medicine has been increasing in cancer patients. However, there is no systematic review that has been conducted to evaluate the actual benefits of G. lucidum in cancer treatment.
OBJECTIVES:
To evaluate the clinical effects of G. lucidum on long-term survival, tumour response, host immune functions and quality of life in cancer patients, as well as adverse events associated with its use.
SEARCH METHODS:
We searched an extensive set of databases including the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, NIH, AMED, CBM, CNKI, CMCC and VIP Information/Chinese Scientific Journals Database was searched for randomised controlled trials (RCTs) in October 2011. Other strategies used were scanning the references of articles retrieved, handsearching of the International Journal of Medicinal Mushrooms and contact with herbal medicine experts and manufacturers of G. lucidum. For this update we updated the searches in February 2016.
SELECTION CRITERIA:
To be eligible for being included in this review, studies had to be RCTs comparing the efficacy of G. lucidum medications to active or placebo control in patients with cancer that had been diagnosed by pathology. All types and stages of cancer were eligible for inclusion. Trials were not restricted on the basis of language.
DATA COLLECTION AND ANALYSIS:
Five RCTs met the inclusion criteria and were included in this review. Two independent review authors assessed the methodological quality of individual trials. Common primary outcomes were tumour response evaluated according to the World Health Organization (WHO) criteria, immune function parameters such as natural killer (NK)-cell activity and T-lymphocyte co-receptor subsets, and quality of life measured by the Karnofsky scale score. No trial had recorded long-term survival rates. Associated adverse events were reported in one study. A meta-analysis was performed to pool available data from the primary trials. Results were gauged using relative risks (RR) and standard mean differences (SMD) for dichotomous and continuous data respectively, with a 95% confidence interval (CI).
MAIN RESULTS:
The methodological quality of primary studies was generally unsatisfying and the results were reported inadequately in many aspects. Additional information was not available from primary trialists. 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.
AUTHORS' CONCLUSIONS:
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.






Ganoderma lucidum (Reishi mushroom) for cancer treatment.
Jin X1, Ruiz Beguerie J, Sze DM, Chan GC.
Abstract
BACKGROUND:
Ganoderma lucidum is a natural medicine that is widely used and recommended by Asian physicians and naturopaths for its supporting effects on immune system. Laboratory research and a handful of preclinical trials have suggested that G. lucidum carries promising anticancer and immunomodulatory properties. The popularity of taking G. lucidum as an alternative medicine has been increasing in cancer patients. However, there is no systematic review that has been conducted to evaluate the actual benefits of G. lucidum in cancer treatment.
OBJECTIVES:
To evaluate the clinical effects of G. lucidum on long-term survival, tumour response, host immune functions and quality of life in cancer patients, as well as adverse events associated with its use.
SEARCH METHODS:
We searched an extensive set of databases including the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, NIH, AMED, CBM, CNKI, CMCC and VIP Information/Chinese Scientific Journals Database was searched for randomised controlled trials (RCTs) in October 2011. Other strategies used were scanning the references of articles retrieved, handsearching of the International Journal of Medicinal Mushrooms and contact with herbal medicine experts and manufacturers of G. lucidum. For this update we updated the searches in February 2016.
SELECTION CRITERIA:
To be eligible for being included in this review, studies had to be RCTs comparing the efficacy of G. lucidum medications to active or placebo control in patients with cancer that had been diagnosed by pathology. All types and stages of cancer were eligible for inclusion. Trials were not restricted on the basis of language.
DATA COLLECTION AND ANALYSIS:
Five RCTs met the inclusion criteria and were included in this review. Two independent review authors assessed the methodological quality of individual trials. Common primary outcomes were tumour response evaluated according to the World Health Organization (WHO) criteria, immune function parameters such as natural killer (NK)-cell activity and T-lymphocyte co-receptor subsets, and quality of life measured by the Karnofsky scale score. No trial had recorded long-term survival rates. Associated adverse events were reported in one study. A meta-analysis was performed to pool available data from the primary trials. Results were gauged using relative risks (RR) and standard mean differences (SMD) for dichotomous and continuous data respectively, with a 95% confidence interval (CI).
MAIN RESULTS:
The methodological quality of primary studies was generally unsatisfying and the results were reported inadequately in many aspects. Additional information was not available from primary trialists. 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.
AUTHORS' CONCLUSIONS:
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.
A randomized, double-blind and placebo-controlled study of a Ganoderma lucidum polysaccharide extract in neurasthenia.
Tang W1, Gao Y, Chen G, Gao H, Dai X, Ye J, Chan E, Huang M, Zhou S.
Author information
Abstract
Ganoderma lucidum has been widely used to treat various diseases, including cancer, diabetes, and neurasthenia in many Asian countries. This randomized, double-blind, placebo-controlled parallel study aimed to investigate the efficacy and safety of a polysaccharide extract of G. lucidum (Ganopoly) in Chinese patients with neurasthenia. One hundred thirty-two patients with neurasthenia according to the diagnosis criteria of the 10th International Classification of Diseases were included in this study. Written consents were obtained from the patients, and the study was conducted in accordance with Good Clinical Practice guidelines. Patients were randomized to receive Ganopoly or placebo orally at 1,800 mg three times a day for 8 weeks. Efficacy assessments comprised the Clinical Global Impression (CGI) improvement of severity scale and the Visual Analogues Scales for the sense of fatigue and well-being. In 123 assessable patients in two treatment groups at the end of the study, Ganopoly treatment for 8 weeks resulted in significantly lower scores after 8 weeks in the CGI severity score and sense of fatigue, with a respective reduction of 15.5% and 28.3% from baseline, whereas the reductions in the placebo group were 4.9% and 20.1%, respectively. The score at day 56 in the sense of well-being increased from baseline to 38.7% in the Ganopoly group compared with 29.7% in the placebo group. The distribution of the five possible outcomes from very much improved to minimally worse was significantly different (X (2) = 10.55; df = 4; P = .0322) after treatment with Ganopoly or placebo. There was a percentage of 51.6% (32 of 62) in the Ganopoly group rated as more than minimally improved compared with 24.6% (15 of 61) in the placebo group (X (2) = 9.51; df = 1; P = .002). Ganopoly was well tolerated in the study patients. These findings indicated that Ganopoly was significantly superior to placebo with respect to the clinical improvement of symptoms in neurasthenia.





Potential of a novel polysaccharide preparation (GLPP) from Anhui-grown Ganoderma lucidum in tumor treatment and immunostimulation.
Pang X1, Chen Z, Gao X, Liu W, Slavin M, Yao W, Yu LL.
Author information
Abstract
Growing evidence indicates the potential of developing novel polysaccharide-based adjuvant for tumor therapy from edible mushrooms, including Ganoderma lucidum. In the present study, a novel polysaccharide preparation (GLPP) was isolated from the fruiting body of G. lucidum grown in Anhui, China, and characterized for its physicochemical properties. GLPP had an average molecular weight of 6600 and a specific optical rotation of +25.6 degrees , contained 10.6% protein, and had a molar ratio of 0.9:15:1 for mannose, glucose, and galactose, respectively. GLPP was also investigated and compared with PSP (polysaccharopeptide preparation), a commercial antitumor and immunostimulating agent, for its antitumor and immunostimulation capacity, and potential in reducing the toxic effects induced by cyclophosphamide (Cy) treatment and Cobalt-60 ((60)Co) radiation in mice. GLPP at levels of 100 and 300 mg/kg body weight (BW)/d significantly inhibited the growth of inoculated S(180), Heps, and EAC tumor cells in mice. GLPP at a dose of 300 mg/kg BW/d showed stronger growth inhibition against all 3 tested tumor cells than PSP at 1 g/kg BW/d. GLPP also dose-dependently increased phagocytic index, phagocytic coefficient, and 50% hemolysin value in the EAC tumor-bearing mice, indicating its potential immunostimulating property. In addition, GLPP at 300 mg/kg BW/d was comparable to PSP at 1000 mg/kg BW/d in preventing the decrease of thymus index, spleen index, white blood cells, and bone marrow karyote numbers induced by Cy treatment and (60)Co radiation. These data demonstrated the potential utilization of GLPP as an adjuvant to conventional treatments of cancers and its use for cancer prevention.







Triterpenoids from Ganoderma lucidum and their cytotoxic activities.
Li P1, Deng YP, Wei XX, Xu JH.
Author information
Abstract
From the ethyl acetate fraction of the fruiting body of Ganoderma lucidum, a new triterpenoid, ethyl 7β-hydroxy-4,4,14α-trimethyl-3,11,15-trioxo-5α-chol-8-en-24-oate (4), named ethyl lucidenates A, along with three known compounds, ganodermanondiol (1), lucidumol B (2) and methyl lucidenates A (3) were isolated by silica gel column, ODS column chromatography and PHPLC. Their structures were established on the basis of spectroscopic analysis and chemical evidence. The isolated compounds were tested using in vitro MTT assay for their cytotoxic activities against the K562, HL-60, CA46, HepG2, SW480 and SMMC-7221 cancer cell lines. Among them, compound 4 showed cytotoxicity against HL-60 and CA46 cancer cell lines with IC(50) values of 25.98 and 20.42 µg mL(-1), respectively.
PMID: 
22263904 
DOI: 
10.1080/14786419.2011.652961








Suppression of the inflammatory response by triterpenes isolated from the mushroom Ganoderma lucidum.
Dudhgaonkar S1, Thyagarajan A, Sliva D.
Author information
Abstract
Ganoderma lucidum is a popular medicinal mushroom, which has been used in the Traditional Chinese medicine for the prevention or treatment of a variety of diseases. In the present study we evaluated the anti-inflammatory effects of the triterpene extract from G. lucidum (GLT) in LPS-stimulated macrophages. Here we show that GLT markedly suppressed the secretion of inflammatory cytokine tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6), and inflammatory mediator nitric oxide (NO) and prostaglandin E(2) (PGE(2)) from lipopolysaccharide (LPS)-stimulated murine RAW264.7 cells. GLT also down-regulated LPS-dependent expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX-2) in RAW264.7 cells. The anti-inflammatory effects of GLT were mediated by the inhibition of transcription factor NF-kappaB as demonstrated by decreased NF-kappaB-DNA binding activity, and the suppression of p65 phosphorylation in LPS-stimulated macrophages treated with GLT. Moreover, GLT inhibited LPS-dependent AP-1-DNA binding activity and down-regulated expression of AP-1 subunit c-Jun. In addition, GLT suppressed the activity of MAP kinases as observed by the down-regulation of LPS-induced phosphorylation of ERK1/2 and JNK but not p38. In vivo experiments clearly demonstrated that GLT also inhibited the production of TNF-alpha and IL-6 in LPS-induced endotoxemic mice. Apart from its anti-inflammatory activity, GLT suppressed cell proliferation of RAW264.7 cells through cell cycle arrest at G0/G1-G2M, which was mediated by the down-regulation of expression of cell cycle regulatory proteins cyclin D1, CDK4 and cyclin B1, respectively. In conclusion, the anti-inflammatory and anti-proliferative effects of GLT on macrophages are mediated through the inhibition of NF-kappaB and AP-1 signaling pathways.






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.







Ganoderma lucidum (Reishi mushroom) for cancer treatment.
Jin X1, Ruiz Beguerie J, Sze DM, Chan GC.
Ganoderma lucidum (Reishi mushroom) for cancer treatment. [Cochrane Database Syst Rev. 2016]
Abstract
BACKGROUND:
Ganoderma lucidum is a natural medicine that is widely used and recommended by Asian physicians and naturopaths for its supporting effects on immune system. Laboratory research and a handful of preclinical trials have suggested that G. lucidum carries promising anticancer and immunomodulatory properties. The popularity of taking G. lucidum as an alternative medicine has been increasing in cancer patients. However, there is no systematic review that has been conducted to evaluate the actual benefits of G. lucidum in cancer treatment.
OBJECTIVES:
To evaluate the clinical effects of G. lucidum on long-term survival, tumour response, host immune functions and quality of life in cancer patients, as well as adverse events associated with its use.
SEARCH METHODS:
The authors ran an extensive set of databases including the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, NIH, AMED, CBM, CNKI, CMCC and VIP Information/Chinese Scientific Journals Database was searched for randomised controlled trials (RCTs) in October 2011. Other strategies used were scanning the references of articles retrieved, handsearching of the International Journal of Medicinal Mushrooms and contact with herbal medicine experts and manufacturers of G. lucidum.
SELECTION CRITERIA:
To be eligible for being included in this review, studies had to be RCTs comparing the efficacy of G. lucidum medications to active or placebo control in patients with cancer that had been diagnosed by pathology. All types and stages of cancer were eligible for inclusion. Trials were not restricted on the basis of language.
DATA COLLECTION AND ANALYSIS:
Five RCTs met the inclusion criteria and were included in this review. Two independent review authors were assigned to assess the methodological quality of individual trials. Common primary outcomes were tumour response evaluated according to the World Health Organization (WHO) criteria, immune function parameters such as natural killer (NK)-cell activity and T-lymphocyte co-receptor subsets, and quality of life measured by the Karnofsky scale score. No trial had recorded long-term survival rates. Associated adverse events were reported in one study. A meta-analysis was performed to pool available data from the primary trials. Results were gauged using relative risks (RR) and standard mean differences (SMD) for dichotomous and continuous data respectively, with a 95% confidence interval (CI).
MAIN RESULTS:
The methodological quality of primary studies was generally unsatisfying and the results were reported inadequately in many aspects. Additional information was not available from primary trialists. 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.
AUTHORS' CONCLUSIONS:
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.
Antidepressant-like effects of a water-soluble extract from the culture medium of Ganoderma lucidum mycelia in rats.
Matsuzaki H, Shimizu Y, Iwata N, Kamiuchi S, Suzuki F, Iizuka H, Hibino Y, Okazaki M1.
Author information
Abstract
BACKGROUND:
Ganoderma lucidum is a popular medicinal mushroom used for promoting health and longevity in Asian countries. Previously, we reported that a water-soluble extract from a culture medium of Ganoderma lucidum mycelia (MAK) exerts antioxidative and cerebroprotective effects against ischemia-reperfusion injury in vivo. Here, we evaluated the antidepressant and anxiolytic activities of MAK in rats.
METHODS:
MAK (0.3 or 1 g/kg, p.o.) was administered in the experimental animals 60 min before the forced swimming, open-field, elevated plus-maze, contextual fear-conditioning, and head twitch tests. Additionally, the mechanisms involved in the antidepressant-like action of MAK were investigated by the serotonin precursor 5-hydroxy-L-tryptophan (5-HTP)- or 5-HT2A agonist (±)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane hydrochloride (DOI)-induced head twitch responses.
RESULTS:
Treatment with MAK (1 g/kg) exhibited antidepressant-like effects in the forced swimming test, attenuated freezing behavior in the contextual fear-conditioning test, and decreased the number of head twitches induced by DOI, but not with 5-HTP. No significant response was observed in locomotion or anxiety-like behavior, when the animals were evaluated in the open-field or elevated plus-maze test, respectively.
CONCLUSIONS:
These data suggest that MAK has antidepressant-like potential, which is most likely due to the antagonism of 5-HT2A receptors, and possesses anxiolytic-like effects toward memory-dependent and/or stress-induced anxiety in rats.







β-Glucan from Lentinus edodes Inhibits Nitric Oxide and Tumor Necrosis Factor-α Production and Phosphorylation of Mitogen-activated Protein Kinases in Lipopolysaccharide-stimulated Murine RAW 264.7 Macrophages*
+Author Affiliations
1. ↵1 To whom correspondence may be addressed. Tel.: 86-27-8721-6311; Fax: 86-27-6875-4067; E-mail: xuxj626@263.net.
2. ↵2 To whom correspondence may be addressed. Tel./Fax: 81-78-803-5878; E-mail: ashida@kobe-u.ac.jp.
Capsule
Background: High level of NO and TNF-α can induce diverse effects on host survival.
Results: Lentinan inhibits NO and TNF-α secretion and phosphorylation of MAP kinases JNK1/2 and ERK1/2.
Conclusion: Inhibition of NO and TNF-α is partially through suppression of JNK1/2 and ERK1/2 activation.
Significance: A novel pharmacological molecule is discovered to control the diseases associated with NO and TNF-α overproduction.
Abstract
Lentinan (LNT), a β-glucan from the fruiting bodies of Lentinus edodes, is well known to have immunomodulatory activity. NO and TNF-α are associated with many inflammatory diseases. In this study, we investigated the effects of LNT extracted by sonication (LNT-S) on the NO and TNF-α production in LPS-stimulated murine RAW 264.7 macrophages. The results suggested that treatment with LNT-S not only resulted in the striking inhibition of TNF-α and NO production in LPS-activated macrophage RAW 264.7 cells, but also the protein expression of inducible NOS (iNOS) and the gene expression of iNOS mRNA and TNF-α mRNA. It is surprising that LNT-S enhanced LPS-induced NF-κB p65 nuclear translocation and NF-κB luciferase activity, but severely inhibited the phosphorylation of JNK1/2 and ERK1/2. The neutralizing antibodies of anti-Dectin-1 and anti-TLR2 hardly affected the inhibition of NO production. All of these results suggested that the suppression of LPS-induced NO and TNF-α production was at least partially attributable to the inhibition of JNK1/2 and ERK1/2 activation. This work discovered a promising molecule to control the diseases associated with overproduction of NO and TNF-α.



Aqueous extracts of Lentinula edodes and Pleurotus sajor-caju exhibit high antioxidant capability and promising in vitro antitumor activity

T.C.FinimundyaG.GambatoaR.FontanabM.CamassolabM.SalvadorcS.MouradJ.HessefJ.A.P.HenriquesaA.J.P.DillonbM.Roesch-Elya
Abstract
Mushroom extracts are increasingly sold as dietary supplements because of several of their properties, including the enhancement of immune function and antitumor activity. We hypothesized that soluble polar substances present in mushroom extracts may show antioxidant and anticancer properties. This report shows that Brazilian aqueous extracts of Lentinula edodes and Pleurotus sajor-caju exert inhibitory activity against the proliferation of the human tumor cell lines laryngeal carcinoma (Hep-2) and cervical adenocarcinoma (HeLa). Cell viability was determined after using 3 different temperatures (4°C, 22°C, and 50°C) for mushroom extraction. Biochemical assays carried out in parallel indicated higher amounts of polyphenols in the L edodes extracts at all extraction temperatures investigated. The scavenging ability of the 2,2-diphenyl-1-picrylhydrazyl radical showed higher activity for L edodes extracts. Superoxide dismutase–like activity showed no statistically significant difference among the groups for the 2 tested extracts, and catalase-like activity was increased with the L edodes extracts at 4°C. The results for the cytotoxic activity from P sajor-caju extracts at 22°C revealed the half maximal inhibitory concentration values of 0.64% ± 0.02% for Hep-2 and 0.25% ± 0.02% for HeLa. A higher cytotoxic activity was found for the L edodes extract at 22°C, with half maximal inhibitory concentration values of 0.78% ± 0.02% for Hep-2 and 0.57% ± 0.01% for HeLa. Substantial morphological modifications in cells were confirmed by Giemsa staining after treatment with either extract, suggesting inhibition of proliferation and induction of apoptosis with increasing extract concentrations. These results indicate that the aqueous extracts of Brazilian L edodes and P sajor-caju mushrooms are potential sources of antioxidant and anticancer compounds. However, further investigations are needed to exploit their valuable therapeutic uses and to elucidate their modes of action.




Direct Cytotoxicity of Lentinula edodes Mycelia Extract on Human Hepatocellular Carcinoma Cell Line
Hiroshi Yukawa, Satoru Ishikawa, Takashi Kawanishi, Makoto Tamesada, Hironori Tomi
Abstract
Lentinula edodes mycelia (L.E.M.) is a dried powder extracted from shiitake mushrooms (Lentinula edodes). We previously demonstrated that it has immunomodulatory effects. In this paper, the direct cytotoxic effects of the polysaccharide-rich fraction of L.E.M. (L.E.M. ethanol precipitate; LEP) on HepG2 human hepatocellular carcinoma (HCC) cells were investigated. LEP directly killed the HepG2 cells efficaciously, but had only minor effects on normal rat hepatocytes and normal mouse dermal cells under the same conditions. Characteristic morphological changes associated with apoptosis such as shrinkage, rounding, and floating as well as chromatin condensation were confirmed; terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) staining was positive as determined by fluorescence microscopy analyses. The caspase-3 and -8 death receptor pathway was found largely responsible for the apoptotic death of HepG2 cells treated with LEP. In conclusion, LEP can directly induce apoptosis of HepG2 cells, and thus may have potential chemotherapeutic applications for the treatment of HCC.







Abstract:
In the last three decades, numerous polysaccharides and polysaccharide-protein complexes have been isolated from mushrooms and used as a source of therapeutic agents. The most promising biopharmacological activities of these biopolymers are their immunomodulation and anti-cancer effects. They are mainly present as glucans with different types of glycosidic linkages such as (1-3), (1-6)-b-glucans and (1-3)-a-glucans, and as true herteroglycans, while others mostly bind to protein residues as polysaccharide-protein complexes. Three antitumor mushroom polysaccharides, i.e. lentinan, schizophyllan and protein-bound polysaccharide (PSK, Krestin), isolated respectively, from Lentinus edodes, Schizophyllum commune and Coriolus versicolor, have become large market items in Japan. Lentinan and schizophyllan are pure b-glucans, whereas PSK is a protein-bound b-glucan. A polysaccharide peptide (PSP), isolated from a strain of Coriolus versicolor in China, has also been widely used as an anti-cancer and immunomodulatory agent. Although the mechansim of their antitumor action is still not completely clear, these polysaccharides and polysaccharide-protein complexes are suggested to enhance cell-mediated immune responses in vivo and in vitro and act as biological response modifiers. Potentiation of the host defense system may result in the activation of many kinds of immune cells that are vitally important for the maintenance of homeostasis. Polysaccharides or polysaccharide-protein complexes are considered as multi-cytokine inducers that are able to induce gene expression of vaious immunomodulatory cytokines and cytokine receptors. Some interesting studies focus on investigation of the relationship between their structure and antitumor activity, elucidation of their antitumor mechanism at the molecular level, and improvement of their various biological activities by chemical modifications.





Antitumor activity of mushroom polysaccharides: a review
Lu Ren,a   Conrad Pereraa  and  Yacine Hemar*a  
 Author affiliations
Abstract
Mushrooms were considered as a special delicacy by early civilizations and valued as a credible source of nutrients including considerable amounts of dietary fiber, minerals, and vitamins (in particularly, vitamin D). Mushrooms are also recognized as functional foods for their bioactive compounds offer huge beneficial impacts on human health. One of those potent bioactives is β-glucan, comprising a backbone of glucose residues linked by β-(1→3)-glycosidic bonds with attached β-(1→6) branch points, which exhibits antitumor and immunostimulating properties. The commercial pharmaceutical products from this polysaccharide source, such as schizophyllan, lentinan, grifolan, PSP (polysaccharide–peptide complex) and PSK (polysaccharide–protein complex), have shown evident clinical results. The immunomodulating action of mushroom polysaccharides is to stimulate natural killer cells, T-cells, B-cells, neutrophils, and macrophage dependent immune system responses via differing receptors involving dectin-1, the toll-like receptor-2 (a class of proteins that play a role in the immune system), scavengers and lactosylceramides. β-Glucans with various structures present distinct affinities toward these receptors to trigger different host responses. Basically, their antitumor abilities are influenced by the molecular mass, branching configuration, conformation, and chemical modification of the polysaccharides. This review aims to integrate the information regarding nutritional, chemical and biological aspects of polysaccharides in mushrooms, which will possibly be employed to elucidate the correlation between their structural features and biological functions.







Efficacy and Safety of Orally Administered Lentinula edodes Mycelia Extract for Patients Undergoing Cancer Chemotherapy: A Pilot Study
Yoshiyuki Yamaguchi

Eiji Miyahara
 and 
Jun Hihara
Abstract
Lentinula edodes mycelia extract (L.E.M.) is extensively utilized as an herbal medicine. However, its safety and effectiveness have not yet been scientifically verified. In this study, we investigated its safety and its influence on quality of life (QOL) and the immune response in patients undergoing cancer chemotherapy. Seven patients were studied in total. The patients were undergoing postoperative adjuvant chemotherapy for breast cancer (n = 3) or gastrointestinal cancer (n = 2), or were receiving chemotherapy to prevent recurrence of gastrointestinal cancer (n = 2). The first course of treatment was chemotherapy alone and the second was chemotherapy plus concomitant administration of L.E.M. Adverse events and changes in the QOL score, lymphocyte subpopulations, lymphocyte activity and serum immune indices were evaluated during the study period. No adverse events attributable to L.E.M. were observed. Compared to the pre-chemotherapy state, no changes in QOL or immune parameters were noted after the first chemotherapy course. In contrast, following the second course of combined therapy, improvements were noted in QOL (p < 0.05), NK cell activity (p < 0.05) and immunosuppressive acidic protein (IAP) (p < 0.01) levels. Although a future large-scale investigation is necessary to confirm these results, these data suggest that the concomitant of L.E.M. with chemotherapy is safe and improves the QOL and immune function of patients undergoing chemotherapy.






An Evidence‐Based Review of a Lentinula edodes Mushroom Extract as Complementary Therapy in the Surgical Oncology Patient
Abstract
The purpose of this review is to present the currently published evidence regarding the use, efficacy, potential mechanisms of action, and results of published clinical trials regarding the use of a Lentinula edodes mushroom–derived extract (active hexose correlated compound) as complementary therapy in patients with cancer. The authors explore the current preclinical and clinical evidence as it relates to this topic and its potential use in the surgical oncology patient. There has been a growing interest in stimulation of the immune system in trauma, cancer, and surgical patients in general. Little, however, has been written about some‐of the supplements in widely used in Japan and China, but relatively unheard of in the United States.









In vitro cytostatic and immunomodulatory properties of the medicinal mushroom Lentinula edodes

Abstract
Lentinula edodes, known as “shiitake” is one of the widely used medicinal mushrooms in the Orient. Antitumour activity of extracts of this mushroom has been widely demonstrated in animals and humans. However, this activity was shown to be host mediated and not by direct cytotoxic activity to cancer cells. This study demonstrates cytotoxic and cell growth inhibitory (cytostatic) effect of aqueous extracts of the mushroom on MCF-7 human breast adenocarcinoma cell line using an MTT cytotoxicity assay. Such effect was demonstrated with fruit body and mycelial extracts, the difference being that there was no significant suppression on normal cells with the latter. Furthermore mycelial extracts did not induce any cytostatic effect in both cancer and normal cell lines based on a DNA synthesis assay. The significant suppression of the proliferation of cancer cells was reflected by the comparatively low IC50 values and the simultaneous higher respective values on normal fibroblast cells. The immunostimulatory activity of both fruit body and mycelial extracts was tested by the lymphocyte transformation test (LTT), which is based on the capacity of active immunomodulators to augment the proliferative response of rat thymocytes to T mitogens in vitro. Both fruit body and mycelial preparations were able to enhance the proliferation of rat thymocytes directly and act as co-stimulators in the presence of the T-mitogen PHA. Interestingly both extracts, similarly to zymosan showed SIcomit/SImit ratios of about 2, indicating adjuvant properties. Overall L. edodes aqueous extracts have demonstrated direct inhibition of the proliferation of human breast cancer cells in vitro and immunostimulatory properties in terms of mitogenic and co-mitogenic activity in vitro.






ANTIOXIDANT PROPERTIES OF LENTINUS EDODES AND AGARICUS BLAZEI EXTRACTS
ABSTRACT
This work aimed to evaluate the antioxidant activity of Lentinus edodes and Agaricus blazei mushrooms, as well as to measure the content of total phenolic compounds of mushroom extracts and verify the oxidative stability of soybean oil added with mushroom extracts that showed higher antioxidant activity according to the methods of the 2,2‐diphenyl‐1‐picrylhydrazyl (DPPH•) free radical scavenging and the β‐carotene/linoleic acid system. According to the DPPH• method, the maximum antioxidant activity for L. edodes and A. blazei methanol extracts was 92.84 and 95.10%, respectively. For the β‐carotene/linoleic acid system, the highest values of antioxidant activity were 93.06% for L. edodes and 78.96% for A. blazei. The content of total phenolic compounds ranged from 7.21 to 128.44 and 26.67 to 134.67 mg gallic acid equivalent/g for L. edodes and A. blazei, respectively. The oxidative stability values provided by the Rancimat method indicated that the two varieties presented similar induction period of 19.85 h.

CONCLUSIONS
The results of the present study showed that, among the studied factors from the extractions, the solvents of different polarities had the highest influence on yield, antioxidant activity and total phenolic compounds of mushrooms, when compared with extraction types, slow and rapid. The methanolic extracts of two mushrooms varieties present the highest antioxidant activity. Moreover, the two mushroom varieties were able to promote good oxidative stability of soybean oil. Therefore, the methanolic extracts of L. edodes and A. blazei are an alternative source of natural antioxidants.






Antioxidant activities of polysaccharides from Lentinus edodes and their significance for disease prevention
Abstract
The crude polysaccharide (LEP) was extracted by hot water from the fruiting bodies of Lentinus edodes, and further purified by DEAE-cellulose and Sepharose CL-6B chromatography, giving three polysaccharide fractions coded as LEPA1, LEPB1 and LEPC1. In this study, their chemical and physical characteristics of polysaccharide fractions and antioxidant capacities, including scavenging activity against hydroxyl radicals, superoxide radicals and Fe2+-chelating ability, were valuated. The results showed that LEPC1 exhibited significantly antioxidant activity at a concentration-dependent manner. Therefore these results indicated that the water-extractable polysaccharide fraction was a potent antioxidant and could be developed to be new health medicine for fighting against various human diseases.






Antibacterial effect of the culture fluid of Lentinus edodes mycelium grown in submerged liquid culture

Abstract
The antimicrobial activity of the culture fluid of Lentinus edodes mycelium grown in submerged liquid culture was tested against some common bacterial species and Candida albicans. The mycelium-free culture fluid was bacteriostatic against Streptococcus pyogenes, Staphylococcus aureus and Bacillus megaterium. The substance responsible for the activity was heat-stable, could be extracted with chloroform and had a molecular weight under 10 000. These characteristics suggested that the component might be lenthionine, an antibacterial and antifungal sulphur-containing compound. The culture fluid was less toxic to human tissue culture cells than to microbes. The antibacterial activity and toxicity could not be attributed to the same component.







Consuming Lentinula edodes (Shiitake) Mushrooms Daily Improves Human Immunity: A Randomized Dietary Intervention in Healthy Young Adults.
Dai X1, Stanilka JM1, Rowe CA1, Esteves EA2, Nieves C Jr1, Spaiser SJ1, Christman MC3, Langkamp-Henken B1, Percival SS1.
Author information
Abstract
BACKGROUND:
Mushrooms are widely cited for their medicinal qualities, yet very few human intervention studies have been done using contemporary guidelines.
OBJECTIVE:
The aim of this study was to determine whether consumption of whole, dried Lentinula edodes (shiitake) mushrooms could improve human immune function. Primary objectives were to ascertain whether L. edodes consumption would improve γδ-T cell proliferation and activation responses, quantify a dose response, and elicit cytokine secretion patterns. Secondary objectives included determining changes in natural killer T (NK-T) cell proliferation and activation, secretory immunoglobulin A (sIgA) in saliva, and C-reactive protein (CRP) in serum.
DESIGN:
Fifty-two healthy males and females, aged 21-41 years, participated in a 4-week parallel group study, consuming either 5 or 10 g of mushrooms daily. Each subject had blood drawn before and after 4 weeks of daily L. edodes consumption. Saliva and serum were also collected. Peripheral blood mononuclear cells were cultured in autologous serum for 24 hours or 6 days, stained, and examined by flow cytometry.
RESULTS:
Eating L. edodes for 4 weeks resulted in increased ex vivo proliferation of γδ-T (60% more, p < 0.0001) and NK-T (2-fold more, p < 0.0001) cells. Both cell types also demonstrated a greater ability to express activation receptors, suggesting that consuming mushrooms improved cell effector function. The increase in sIgA implied improved gut immunity. The reduction in CRP suggested lower inflammation. The pattern of cytokines secreted before and after mushroom consumption was significantly different; consumption resulted in increased interleukin (IL)-4, IL-10, tumor necrosis factor (TNF)-α, and IL-1α levels, a decreased macrophage inflammatory protein-1α/chemokine C-C ligand 3 (MIP-1α/CCL3) level, and no change to IL-6, IL-1β, MIP-1β, IL-17 and interferon (IFN)-γ levels.
CONCLUSIONS:
Regular L. edodes consumption resulted in improved immunity, as seen by improved cell proliferation and activation and increased sIgA production. The changes observed in cytokine and serum CRP levels suggest that these improvements occurred under conditions that were less inflammatory than those that existed before consumption.





Lentinula edodes-derived polysaccharide enhances systemic and mucosal immunity by spatial modulation of intestinal gene expression in mice.
Xu X1, Yang J, Luo Z, Zhang X.
Author information
Abstract
Mushroom polysaccharides have been reported to possess significant biological activities. However, their molecular mechanisms are not fully elucidated. In this study, the immunostimulating activity of a newly purified heteropolysaccharide L2 from Lentinula edodes is evaluated in Caco-2 cells and a Caco-2/RAW264.7 co-culture system, as well as in mice. Subsequently, the customized RT-PCR array containing 112 genes is employed to investigate the effects of L2 on gene expressions in the small intestine, cecum and colon. The results show that L2 significantly enhances immune responses by differentially affecting the gene expressions of small intestine, cecum and colon, in which 55, 26 and 25 genes are markedly changed, respectively. In particular, 3 core regulation networks are identified for various parts of gut. These data demonstrate the potential of L2 as a potent immune stimulator and for the first time provide a detailed landscape of tissue-specific gene expressions and core regulation networks in response to L. edodes-derived heteropolysaccharide treatment.







Lentinula edodes-derived polysaccharide rejuvenates mice in terms of immune responses and gut microbiota.
Xu X1, Yang J, Ning Z, Zhang X.
Author information
Abstract
Aging is characterized by impaired immunity and unbalanced gut microbiota. Prebiotics have the capability to prevent or reverse age-related declines in health by modulating gut microbiota. Mushroom polysaccharides have been suggested to be potential prebiotics. However, their effects on the immunity and gut microbiota in aged mice have not been determined. This study firstly assessed the effects of a heteropolysaccharide L2 isolated from the fruit body of L. edodes on the immune response of aged mice, and then compared the composition of fecal microbiota in adult (N), old (O) and L2-treated old (Oa) mice using the high-throughput pyrosequencing technique. The results showed that L2 can restore the age-attenuated immune responses by increasing cytokine levels in peripheral blood. Moreover, L2 can partly reverse the age-altered composition of gut microbiota. The Euclidean distances (De) among 3 groups (N, O and Oa) are determined to be De(O, N) = 0.19, De(O, Oa) = 0.20, and De(N, Oa) = 0.10, i.e. there is a marked reduction in the distance from 0.19 to 0.1 by L2. This suggests the beneficial effects of L2 on enhancing immunity and improving gut health.







Polysaccharides in Lentinus edodes: isolation, structure, immunomodulating activity and future prospective.
Xu X1, Yan H, Tang J, Chen J, Zhang X.
Author information
Abstract
Lentinus edodes has been valued as edible and medical resources. Polysaccharides have been known to be the most potent antitumor and immunomodulating substance in Lentinus edodes. In this review, we summarize the current knowledge of the polysaccharides isolated from Lentinus edodes, including extraction and purification methods, chemical structure and chain conformation, the effects on innate and adaptive immunity and their mechanism, relationship between structure and function, and the future prospects.







Recent developments in mushrooms as anti-cancer therapeutics: a review
Seema Patel and Arun Goyal
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Abstract
From time immemorial, mushrooms have been valued by humankind as a culinary wonder and folk medicine in Oriental practice. The last decade has witnessed the overwhelming interest of western research fraternity in pharmaceutical potential of mushrooms. The chief medicinal uses of mushrooms discovered so far are as anti-oxidant, anti-diabetic, hypocholesterolemic, anti-tumor, anti-cancer, immunomodulatory, anti-allergic, nephroprotective, and anti-microbial agents. The mushrooms credited with success against cancer belong to the genus Phellinus, Pleurotus, Agaricus, Ganoderma, Clitocybe, Antrodia, Trametes, Cordyceps, Xerocomus, Calvatia, Schizophyllum, Flammulina, Suillus, Inonotus, Inocybe, Funlia, Lactarius, Albatrellus, Russula, and Fomes. The anti-cancer compounds play crucial role as reactive oxygen species inducer, mitotic kinase inhibitor, anti-mitotic, angiogenesis inhibitor, topoisomerase inhibitor, leading to apoptosis, and eventually checking cancer proliferation. The present review updates the recent findings on the pharmacologically active compounds, their anti-tumor potential, and underlying mechanism of biological action in order to raise awareness for further investigations to develop cancer therapeutics from mushrooms. The mounting evidences from various research groups across the globe, regarding anti-tumor application of mushroom extracts unarguably make it a fast-track research area worth mass attention.






Dietary calcium and vitamin D2 supplementation with enhanced Lentinula edodes improves osteoporosis-like symptoms and induces duodenal and renal active calcium transport gene expression in mice.
Lee GS1, Byun HS, Yoon KH, Lee JS, Choi KC, Jeung EB.
Author information
Abstract
The two main sources of vitamin D3 are de novo synthesis induced by exposure to ultraviolet (UV) light from the sun, and diet. Vitamin D3 deficiency causes rickets or osteoporosis. Oak mushrooms (Lentinula edodes) that are exposed to UV radiation contain enhanced vitamin D2 and have much higher calcium content than unmodified (non-irradiated) mushrooms. Such modified edible mushrooms have been proposed as a natural alternative source of dietary vitamin D. In the current study, we have examined whether modified oak mushrooms could improve or prevent osteoporosis-like symptoms in mice fed with low calcium and vitamin D3-deficient diet. Four-week-old male mice were fed low calcium, vitamin D3-deficient diets supplemented with 5, 10, or 20% unmodified, calcium-enhanced, or calcium plus vitamin D2-enhanced oak mushrooms for 4 weeks. To assess the effects of the supplemented diets, we evaluated femur density and length, bone histology, the expression of active calcium transport genes, and serum calcium levels. Mice fed with low calcium and vitamin D3-deficient diet developed osteoporosis-like symptoms within 4 weeks. Femur density and tibia thickness were significantly higher in mice fed calcium plus vitamin D2-enhanced mushrooms, and the expression of duodenal and renal calcium transport genes was significantly induced. These results indicate that in mice, vitamin D2 and/or calcium derived from irradiated oak mushrooms may improve bone mineralization through a direct effect on the bone, and by inducing the expression of calcium-absorbing genes in the duodenum and kidney.






Antigenotoxic Effect of Trametes spp. Extracts against DNA Damage on Human Peripheral White Blood Cells
Aleksandar Knežević, Lada Živković, [...], and Biljana Spremo-Potparević
Additional article information
Abstract
Trametes species have been used for thousands of years in traditional and conventional medicine for the treatment of various types of diseases. The goal was to evaluate possible antigenotoxic effects of mycelium and basidiocarp extracts of selected Trametes species and to assess dependence on their antioxidant potential. Trametes versicolor, T. hirsuta, and T. gibbosa were the species studied. Antigenotoxic potentials of extracts were assessed on human peripheral white blood cells with basidiocarp and mycelium extracts of the species. The alkaline comet test was used for detection of DNA strand breaks and alkali-labile sites, as well as the extent of DNA migration. DPPH assay was used to estimate antioxidative properties of extracts. Fruiting body extracts of T. versicolor and T. gibbosa as well as T. hirsuta extracts, except that at 20.0 mg/mL, were not genotoxic agents. T. versicolor extract had at 5.0 mg/mL the greatest antigenotoxic effect in both pre- and posttreatment of leukocytes. The mycelium extracts of the three species had no genotoxic activity and significant antigenotoxic effect against H2O2-induced DNA damage, both in pre- and posttreatment. The results suggest that extracts of these three species could be considered as strong antigenotoxic agents able to stimulate genoprotective response of cells.






The lignicolous fungus Trametes versicolor (L.) Lloyd (1920): a promising natural source of antiradical and AChE inhibitory agents
Ljiljana Janjušević, Maja Karaman, [...], and Boris Pejin
Additional article information
Abstract
This study aimed to determine antiradical (DPPH• and •OH) and acetylcholinesterase (AChE) inhibitory activities along with chemical composition of autochtonous fungal species Trametes versicolor (Serbia). A total of 38 phenolic compounds with notable presence of phenolic acids were identified using HPLC/MS-MS. Its water extract exhibited the highest antiradical activity against •OH (3.21 μg/mL), among the rest due to the presence of gallic, p-coumaric and caffeic acids. At the concentration of 100 μg/mL, the same extract displayed a profound AChE inhibitory activity (60.53%) in liquid, compared to donepezil (89.05%), a drug in clinical practice used as positive control. The flavonoids baicalein and quercetin may be responsible compounds for the AChE inhibitory activity observed. These findings have demonstrated considerable potential of T. versicolor water extract as a natural source of antioxidant(s) and/or AChE inhibitor(s) to be eventually used as drug-like compounds or food supplements in the treatment of Alzheimer’s disease.





Cytotoxic activities of Coriolus versicolor (Yunzhi) extracts on human liver cancer and breast cancer cell line
X Zhou, H Jiang, J Lin, K Tang

Abstract

The CVP (Coriolus versicolor polysaccharide) is well known as anti-tumor drug in clinical applications. Although recent studies have demonstrated that CVP can inhibit the proliferation of cancer cells in vitro and in vivo, the different purity level of CVP has a different affect on various cancer cells. In this study, the crude CVP was extracted from C. versicolor dry fruit bodies by hot-water extraction and ethanol
precipitation. The content of CVP was 7.74% in the fruit bodies, while 54.69% in the crude extracts by phenol-vitriolic colorimetry. After that, the in vitro cytotoxic activities of the CVP were examined on the
four human liver cancer (7703, HepG2, 7721, PLC) and four human breast cancer (Bcap37, ZR75-30, MCF-7, T-47D) cell lines using a MTT cytotoxicity assay. The results showed that the CVP inhibited the
proliferation of 7703, Bcap37, T-47D in low concentration; the IC50 values on 7703, Bcap37 and T-47D were 18.37, 14.42 and 9.29 mg/l, respectively. The CVP also inhibited the proliferation of MCF-7 and
ZR75-30, but at high concentration, the IC50 values on MCF-7 and ZR75-30 were 39.26 and 34.59 mg/l, respectively. The CVP does not inhibit the proliferation of HepG2, 7721, PLC and human normal liver
cell line (WRL). The CVP was found to selectively inhibit the proliferation of human liver cancer and human breast cancer.






Cytotoxic activities of Coriolus versicolor (Yunzhi) extract on human leukemia and lymphoma cells by induction of apoptosis
C.B.SLauaC.YHoaC.FKimaK.NLeungbK.PFungbT.FTsecH.H.LChancM.S.SChowa
Abstract
Coriolus versicolor (CV), also known as Yunzhi, is one of the commonly used Chinese medicinal herbs. Although recent studies have demonstrated its antitumour activities on cancer cells in vitro and in vivo, the exact mechanism is not fully elucidated. Hence, the objective of this study was to examine the in vitro cytotoxic activities of a standardized aqueous ethanol extract prepared from Coriolus versicolor on a B-cell lymphoma (Raji) and two human promyelocytic leukemia (HL-60, NB-4) cell lines using a MTT cytotoxicity assay, and to test whether the mechanism involves induction of apoptosis. Cell death ELISA was employed to quantify the nucleosome production resulting from nuclear DNA fragmentation during apoptosis. The present results demonstrated that CV extract at 50 to 800 μg/ml dose-dependently suppressed the proliferation of Raji, NB-4, and HL-60 cells by more than 90% (p < 0.01), with ascending order of IC50 values: HL-60 (147.3 ± 15.2 μg/ml), Raji (253.8 ± 60.7 μg/ml) and NB-4 (269.3 ± 12.4 μg/ml). The extract however did not exert any significant cytotoxic effect on normal liver cell line WRL (IC50 > 800 μg/ml) when compared with a chemotherapeutic anticancer drug, mitomycin C (MMC), confirming the tumour-selective cytotoxicity. Nucleosome productions in HL-60, NB-4 and Raji cells were significantly increased by 3.6-, 3.6- and 5.6-fold respectively upon the treatment of CV extract, while no significant nucleosome production was detected in extract-treated WRL cells. The CV extract was found to selectively and dose-dependently inhibit the proliferation of lymphoma and leukemic cells possibly via an apoptosis-dependent pathway.





Authors: T C Hsieh  J M Wu

Abstract
The incidence of prostate cancer varies greatly throughout the world; it is highest in African-Americans and lowest in the Asian populations of China, India, and Japan. Geographical differences in both prevalence of latent prostate cancer and mortality have been postulated to be influenced by diverse tumor-promoting and protective factors, both environmental and dietary. Prostate cancer is a tumor with an extremely long latency; the pattern of prostate tumorigenesis, in terms of the display and sequence of appearance of particular molecular or biochemical features, or morphological changes, characterizing different stages of the carcinogenic process, is expected to be heterogeneous. Some insights into tumor heterogeneity and progression can be obtained from studies using cell lines, particularly those derived from different anatomical sites. The present study aims to investigate whether hormone-responsive LNCaP and androgen-refractory JCA-1, PC-3, and DU-145 prostate cancer cells are responsive to Yunzhi (YZ), a proprietary dietary supplement prepared from extracts of Trametes versicolor, also known as Coriolus versicolor (a mushroom consumed by Chinese for its purported health benefits), and to elucidate its mechanism of action. Ethanolic extracts (70%) of YZ significantly reduced LNCaP cell growth, down-regulated the levels of secreted PSA, but had less effects on the expression of intracellular PSA and did not affect levels of the androgen receptor. In androgen-unresponsive prostate cancer cells, YZ had a much less pronounced suppressive effect on proliferation of PC-3 and DU-145 cells, compared to LNCaP, and was inactive against JCA-1 cells. Western blot analyses show that the expression of Rb, a key regulatory protein in G1/S transition, and PCNA, integrally involved in mammalian cell DNA replication, were significantly reduced by treatment with YZ in PC-3 and DU-145 cells, respectively. In contradiction, none of these biochemical parameters were affected in JCA-1 cells under identical treatment conditions. Further analysis shows that YZ increased the levels of signal transducer and activator family of transcription factors STAT 1 and STAT 3 in JCA-1 and not LNCaP cells. The greater sensitivity of LNCaP cells to this polysaccharopeptide raises the possibility that YZ may be considered as an adjuvant therapy in the treatment of hormone responsive prostate cancer; additionally, it may have chemopreventive potential to restrict prostate tumorigenic progression from the hormone-dependent to the hormone-refractory state.







Trametes versicolor (Turkey Tail Mushrooms) and the Treatment of Breast Cancer
Paul Edward Stamets
“PS,” an 83-year-old woman, was diagnosed in June 2009 with advanced, metastatic inflammatory breast cancer. At the same time, she began chemo-therapy with Taxol and Herceptin, she also began taking capsules of turkey tail mushroom daily. The dose was 4 g twice daily (Host Defense Turkey Tail capsules, Fungi Perfecti Laboratories, Kamilche Point, Washington). The turkey tail capsules consist of activated, freeze-dried, organic mushroom mycelium, containing polysaccharides (beta-glucans, arabinoxylane, glucose, xylose, galactose, mannose, glycoproteins, ergosterols, triterpenoids, and other myconutrients). In December 2009, when the patient's chemotherapy regimen was completed and she began Herceptin maintenance therapy every 3 weeks, she continued to take 4 g daily of turkey tail mushrooms and added a combination mushroom formula (Host Defense MyCommunity capsules, Fungi Perfecti, Laboratories). This preparation consisted of 17 species of activated, freeze-dried, organic mushroom mycelium, containing polysaccharides (beta-glucans, arabinoxylane, glucose, xylose, galactose, cordycepic acid, glycoproteins, ergosterols, triterpenoids, and other myconutrients). Turkey tail mushrooms grow in a woodland environment worldwide and have been reported to stimulate immune function in women with breast cancer. They are called bracket fungi because they form thin structures in concentric circles and grow almost everywhere trees are found. This species of mushrooms has a history of use in Asia as a nonspecific immune modulator, and in breast cancer patients, they have been shown to interact with the CR3 membrane receptors for beta-glucans.1 Immune modulation is believed to be the primary mechanism of action of turkey tail mushrooms.2 The University of Minnesota and Bastyr University (Kenmore, Washington) recently completed a phase 1 dose-escalation trial and found that up to 9 g/day of a T versicolor preparation is safe and tolerable in women with breast cancer who had undergone chemotherapy.3 Perhaps the most intriguing part of this study was the finding that 6 g of T versicolor appeared to lead to faster immune recovery after radiotherapy. This should be studied in additional clinical trials on the potential primary and secondary effects of mushroom therapy in patients with cancer and, more specifically, cancers with altered CR3 membrane receptors. T versicolor growing in its natural habitat. My hypothesis is that that the documented immune modulation activity of the turkey tail mushrooms enhanced the ability of the patient's immune system to discover the tumor, thereby increasing the effectiveness of the chemotherapy. This is consistent with some of the basic science research describing medicinal mushrooms as modulators of molecular targets in cancer treatment. Three and one-half years later, this now 87-year-old patient leads a vital and active life, is disease free, and in addition to being administered Herceptin every 3 weeks, takes a daily dose of turkey tail mushrooms and a 17-species mushroom formula. LESS
Novel medicinal mushroom blend suppresses growth and invasiveness of human breast cancer cells

Authors: 
Jiahua Jiang 
Daniel Sliva


Abstract
Mushrooms are an integral part of Traditional Chinese Medicine (TCM), and have been used for millennia to prevent or treat a variety of diseases. Currently mushrooms or their extracts are used globally in the form of dietary supplements. In the present study we have evaluated the anticancer effects of the dietary supplement, MycoPhyto® Complex (MC), a novel medicinal mushroom blend which consists of a blend of mushroom mycelia from the species Agaricus blazei, Cordyceps sinensis, Coriolus versicolor, Ganoderma lucidum, Grifola frondosa and Polyporus umbellatus, and β-1,3-glucan isolated from the yeast, Saccharomyces cerevisiae. Here, we show that MC demonstrates cytostatic effects through the inhibition of cell proliferation and cell cycle arrest at the G2/M phase of highly invasive human breast cancer cells MDA-MB-231. DNA-microarray analysis revealed that MC inhibits expression of cell cycle regulatory genes (ANAPC2, ANAPC2, BIRC5, Cyclin B1, Cyclin H, CDC20, CDK2, CKS1B, Cullin 1, E2F1, KPNA2, PKMYT1 and TFDP1). Moreover, MC also suppresses the metastatic behavior of MDA-MB-231 by the inhibition of cell adhesion, cell migration and cell invasion. The potency of MC to inhibit invasiveness of breast cancer cells is linked to the suppression of secretion of the urokinase plasminogen activator (uPA) from MDA-MB-231 cells. In conclusion, the MC dietary supplement could have potential therapeutic value in the treatment of invasive human breast cancer.